High-sensitivity C-reactive protein and left ventricular remodeling in patients with acute myocardial infarction

Inflammatory cytokines are suspected to play an important role in the pathophysiology of left ventricular (LV) remodeling. We investigated whether high-sensitivity C-reactive protein (CRP) (hs-CRP) is a predictor for LV remodeling in patients with acute myocardial infarction (AMI) with successful reperfusion, and also whether such a situation can be avoided by the administration of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor blockers (ARB). The subjects were 139 patients with an initial attack of anterior myocardial infarction successfully treated by reperfusion therapy. They were randomly divided into the following two groups: an angiotensin (AG) group (91 patients treated with ACEI/ARB) and a NON-AG group (48 patients not treated with ACEI/ARB). Levels of hs-CRP, creatine kinase, human atrial natriuretic polypeptide, brain natriuretic peptide (BNP), fasting blood glucose, serum lipids, fibrinogen, fibrin degradation product, prothromloin time, and activated partial thromboplastin time were measured immediately after 1, 2, 3, and 7 days, and 1 months after the onset of AMI. ACEI or ARB administration lowered hs-CRP levels and prevented the development of LV remodeling. Peak CRP levels significantly correlated with BNP levels during the acute stage (r = +0.54, P < 0.0001), end-diastolic volume index (r = +0.78, P < 0.0001), end-systolic volume index (r = +0.36, P = 0.0405), ejection fraction (r = -0.45, P = 0.0052), left ventricular end-diastolic diameter (r = +0.61, P < 0.0001), cardiac output (r = -0.52, P = 0.0005), cardiac index (r = -0.41, P = 0.0099), and systolic pulmonary arterial pressure (r = +0.48, P = 0.0017) 1 month after the onset of AMI in the NON-AG group but not in the AG group. Logistic multivariate analysis revealed that peak CRP alone was an independent risk factor for the development of LV remodeling in the NON-AG group (odds ratio = 1.79, P = 0.002). These results suggest that hs-CRP is a useful factor for predicting LV remodeling. Furthermore, ACEI or ARB administration to AMI patients showing increased hs-CRP levels during the early stage of the disease could prevent LV remodeling.


Myocardial perfusion magnetic resonance imaging for diagnosing coronary arterial stenosis:evaluation by signal-intensity time curves

It has been reported that myocardial perfusion MRI is a useful method for evaluating the severity of myocardial ischemia. We evaluated whether the severity of coronary arterial stenosis could be assessed by the signal-intensity time curve (SITC) obtained by myocardial perfusion MRI.br The subjects consisted of 10 patients who showed no abnormalities on coronary angiographies (CAG) (A group), 12 with single-vessel disease of 75-90% stenosis on CAG (B group), and 15 with single-vessel disease of 90% or more stenosis (C group). After infusion of dipyridamole for 4 minutes, gadolinium-diethylenetriamine pentaacetic acid was administered intravenously, followed by serial acquisition of T1-weighted left ventricular short-axis MR images. These images were evaluated after dividing them into the following 3 myocardial segments: anterior wall, lateral wall, and inferior wall. Mean values of the slope of SITC (1.4 ± 0.2 vs 1.1 ± 0.2, iP /i 0.01), and increases to the peak corrected SI (ΔSI) (47.5 ± 1.9 % vs 33.7 ± 2.4%, iP/i 0.01) in normal myocardial segments were significantly greater than in ischemic segments in the C group, while there was no significant distinction between normal and ischemic segments in the B group. The mean values of time to the peak SI were not significantly different between normal and ischemic regions in the B and C groups.br The results suggest that myocardial segments exhibiting 30% decreases in both the slope and ΔSI of SITC can be diagnosed as having 90% or more severe coronary stenosis. The present study shows that visual and SITC evaluations of myocardial perfusion MR images may be useful for clinically evaluating the severity of coronary stenosis.br


Effect of human airway trypsin-like protease on intracellular free Ca2+ concentration in human bronchial epithelial cells

It has been shown that human airway trypsin-like protease (HAT) is localized in human bronchial epithelial cells (HBEC), and trypsin activates protease-activated receptor-2 (PAR-2). Activation of PAR-2 activates G-protein followed by an increase of intracellular free Ca2+, [Ca2+]in. This study was undertaken to clarify whether HAT can activate PAR-2 in HBEC or not. RT-PCR showed that HAT mRNA is expressed in HBEC, and PAR-2 mRNA is the most strongly expressed of the known PARs in HBEC. Both PAR-2 agonist peptide (PAR-2 AP) and HAT increased [Ca2+]in in HBEC in a biphasic fashion; a prompt, sharp increase (peak I) and a sustained low plateau (peak II). PAR-2 AP over 100-200 microM and HAT over 200-300 mU/ml (0.08-0.12 microM) induced both peak I and II, and PAR-2 AP below 100 microM and HAT below 200 mU/ml induced only peak II. Both PAR-2 AP-induced and HAT-induced peak I were induced by Ca2+ mobilization from intracellular stores, because they appeared even in Ca2+-free medium. Both PAR-2 AP-induced and HAT-induced peak II were induced by an influx of extracellular Ca2+, because they were abolished in Ca2+-free medium. The Ca2+ response to HAT was desensitized by exposure of HBEC to PAR-2 AP. These results indicate that HBEC have a functional PAR-2, and HAT regulates cellular functions of HBEC via activation of PAR-2.

The Journal of Medical Investigation : JMI


Clinical efficacy of efonidipine hydrochloride, a T-type calcium channel inhibitor, on sympathetic activities --- Examination using spectral analysis of heat rate/blood pressure variabilities and 123I-metaiodobenzylguanidine myocardial scintigraphy

Dihydropyridine Ca antagonists cause reflex tachycardia related to their hypotensive effects. Efonidipine hydrochloride has inhibitory effects on T-type Ca channels, even as it inhibits reflex tachycardia. In the present study, the influence of efonidipine hydrochloride on heart rate and autonomic nervous function was investigated. Using an electrocardiogram and a tonometric blood pressure measurement, autonomic nervous activity was evaluated using spectral analysis of heart rate/systolic blood pressure variability. Three protocols were used: (1) a single dose of efonidipine hydrochloride was administered orally to healthy subjects with resting heart rate values of 75 beats/min or more (high-HR group) and to healthy subjects with resting heart rate values less than 75 beats/min (low-HR group); (2) efonidipine hydrochloride was newly administered to untreated patients with essential hypertension, and autonomic nervous activity was investigated after a 4-week treatment period; and (3) patients with high heart rate values (>/=75 beats/min) who had been treated with a dihydropyridine L-type Ca channel inhibitor for 1 month or more were switched to efonidipine hydrochloride and any changes in autonomic nervous activity were investigated. In all protocols, administration of efonidipine hydrochloride decreased the heart rate in patients with a high heart rate, reduced sympathetic nervous activity, and enhanced parasympathetic nervous activity. In addition, myocardial scintigraphy with (123)I-metaiodobenzylguanidine showed significant improvement in the washout rate and H/M ratio of patients who were switched from other dihydropyridine Ca antagonists to efonidipine hydrochloride. Efonidipine hydrochloride inhibits increases in heart rate and has effects on the autonomic nervous system. It may be useful for treating hypertension and angina pectoris, and may also have a cardiac protective function.


The Journal of Japan Biomagnetism and Bioelectromagnetics Society


Effects of Benidipine Hydrochloride on Autonomic Nervous Activity in Hypertensive Patients with High- and Low-salt Diets

The effects of benidipine hydrochloride (CAS 91559-74-5, Coniel) on autonomic nervous activity in hypertensive patients with high- and low-salt diets were investigated. Six patients having a urinary sodium excretion of 80 mEq/day or less (low salt group) and 6 patients having a urinary sodium excretion of 200 mEq/day or more (high salt group) were orally given benidipine hydrochloride (4 mg). Before and four weeks after the treatment with benidipine, 24-h circadian variation in blood pressure and 24-h Holter electrocardiogram (ECG) were recorded. The low frequency power spectrum of heart rate (LF power; 0.04-0.15 Hz), high frequency power spectrum of heart rate (HF power; 0.15-0.40 Hz), and the ratio of LF to HF (LF/HF) were calculated, and these parameters were averaged every hour in every subject. HF power was significantly lower and LF/HF ratio was significantly higher in the high-salt group than in the low-salt group before the treatment. However, the benidipine treatment significantly increased the HF power in both groups, particularly in the high-salt group, and significantly decreased the LF/HF ratio in both groups. Moreover, there was no significant difference in the antihypertensive effect of benidipine between the high- and low-salt intake groups. These results suggest that benidipine favourably influences blood pressure and autonomic nervous activity in hypertensive patients with a high-salt intake. It is concluded that benidipine may be useful for improving the development of salt-induced hypertension and its accompanying haemodynamic responses.


Influence of mosapride citrate on gastric motility and autonomic nervous function:evaluation by spectral analyses of heart rate and blood pressure variabilities,and by electrogastrography

Mosapride citrate selectively acts on serotonin (5-HT(4)) receptors, thus accelerating gastrointestinal motility via acetylcholine. However, few studies have evaluated the influence of mosapride citrate on autonomic nervous activity and hemodynamics. The changes in autonomic nervous activity, QT interval, and QT dispersion resulting from the administration of mosapride citrate were studied. Blood pressure, electrocardiograms (ECGs), percutaneous electrogastrograms (EGGs), and ultrasonography were recorded in 20 healthy adult volunteers before and after mosapride citrate (10 mg) was administered. Autonomic nervous activity was evaluated by spectral analyses of heart rate and blood pressure variabilities. Serial changes in low-frequency components (LF, 0.04-0.15 Hz), high-frequency components (HF, 0.15-0.40 Hz), and the LF/HF ratio were investigated. The mean peak power of EGG increased significantly, from 86 +/- 34 microV to 131 +/- 49 microV, after the administration of mosapride citrate (P < 0.05). Gastric emptying significantly increased after the administration of mosapride citrate (P < 0.05). However, neither blood pressure nor heart rate changed significantly after the drug was administrated. In addition, spectral analyses of heart rate and blood pressure variabilities showed no significant changes in autonomic nervous activity parameters, QT intervals, or QT dispersions. Mosapride citrate increased gastric motility and emptying without influencing autonomic nervous activity, suggesting that it may be very useful for elderly patients or patients with autonomic imbalance.


Changes in autonomic nervous activity during endoscopic retrograde cholangiopancreatography:a possible factor in cardiac complications.

The changes of autonomic nervous activity during endoscopic retrograde cholangiopancreatography (ERCP) are closely related to the development of cardiovascular complications, such as arrhythmias and acute coronary syndrome. In the present study, the correlation between changes in hemodynamics and autonomic nervous activity during ERCP procedures was evaluated by analyzing heart rate variability and blood catecholamine levels. Twenty-three patients who underwent ERCP (ERCP group) and 15 control subjects who were only premedicated (C group) were studied. Ambulant ECG, blood pressure, arterial oxygen saturation, and blood level of catecholamine were measured. Autonomic nervous function was assessed by analyzing the spectral analysis and 1/f fluctuation. The low frequency power (LF power; 0.04-0.15 Hz), high frequency power (HF power; 0.15-0.40 Hz, indicator of parasymapathetic tone), the ratio of LF power to HF power (LF/HF ratio, indicator of sympathetic tone), and 1/f fluctuation (indicator of pleasant mood) were calculated. Blood pressure and heart rate were increased and arterial oxygen saturation was decreased in the ERCP group during the endoscopic procedure. Changes in the parameters of autonomic nervous function (LF power, HF power, LF/HF ratio, and 1/f fluctuation) were significantly greater in the ERCP group than in the C group, especially during cholangiography. Moreover, blood levels of catecholamines were significantly increased during the ERCP procedure. In the C group, however, blood levels of catecholamines did not significantly change except directly after premedication. Autonomic nervous activity varied greatly during cholangiography, demonstrating that ERCP has more than a little influence on the cardiovascular system. The results of the present study indicated that attention should be focused on changes in hemodynamics in patients with cardiovascular complications by monitoring the aforementioned hemodynamic parameters during ERCP.

Journal of Gastroenterology and Hepatology


Changes in Hemodynamics and Autonomic Nervous Activity in Patients Undergoing Laparoscopic Cholecystectomy:Differences Between the Pneumo-Peritoneum and Abdominal Wall-Lifting Method

Intraoperative changes in circulatory hemodynamics and autonomic nervous activity were evaluated in 33 patients with cholelithiasis who underwent laparoscopic cholecystectomy. Of these patients, 18 were treated using a pneumoperitoneum (group G) and 15 using the abdominal wall-lifting method (group WL). Their ECG, blood pressure, arterial oxygen saturation, and expiratory carbon dioxide partial pressure were monitored. Autonomic nervous function was evaluated by spectral analysis of the heart rate. Mean blood pressure increased significantly in group G during surgery, but did not vary in group WL during any stage of surgery. The high-frequency (HF) power, an index of parasympathetic activity, decreased significantly in group G after pneumoperitoneum. However, the HF power did not decrease significantly in group WL. The LF/HF ratio, an index of sympathetic activity, increased significantly in group G after pneumoperitoneum, but did not vary in group WL. In addition, the incidence of ventricular or supraventricular arrhythmias and the severity of the arrhythmias as determined by Lown's classification were higher in group G than in group WL. These findings suggest that intraoperative changes in autonomic nervous activity, due to increased intra-abdominal pressure, were smaller in patients undergoing laparoscopic cholecystectomy using the abdominal wall-lifting method than in those undergoing laparoscopic cholecystectomy using pneumoperitoneum. The results also demonstrated that hemodynamic changes were smaller in patients undergoing the abdominal wall-lifting method than in those undergoing pneumoperitoneum. It was concluded that hemodynamics should be carefully monitored during pneumoperitoneum, and that the abdominal wall-lifting approach in laparoscopic cholecystectomy is a method worthy of consideration for elderly patients or those with cardiopulmonary complications.


Severe catabolic state after prolonged fasting in cirrhotic patients: effect of oral branched-chain amino-acid-enriched nutrient mixture

Cirrhotic patients frequently undergo various medical procedures, such as diagnostic gastrointestinal endoscopy, without taking breakfast. The aim of the present study was to clarify the effect of longer fasting (> 12 h) on energy metabolism, and to test whether supplementation of an oral branched-chain amino-acid-enriched nutrient mixture (BCAA mixture), which contains various nutrients in addition to BCAA, could improve the catabolic state. Metabolic measurement was performed in 30 cirrhotic patients and 13 normal subjects, using indirect calorimetry. Compared with that in the normal subjects, the respiratory quotient (RQ) was significantly lower after an overnight fast in the cirrhotic patients, indicating accelerated fat oxidation and a catabolic state. In addition, RQ in cirrhotic patients (n = 7) decreased rapidly with longer fasting, whereas that in the normal subjects (n = 5) showed relatively stable values. These results indicate that special care should be taken with medical procedures that are carried out in patients who have fasted. The effect of oral glucose, a carbohydrate-rich snack (rice ball), and the BCAA mixture (each, 210 kcal) on RQ was studied in 6 normal subjects and 6 patients with liver cirrhosis after an overnight fast. Supplementation of the carbohydrate-rich snack and the BCAA mixture (210 kcal each) elevated RQ and blood glucose levels to a similar degree in the cirrhotic patients. Oral administration of glucose (210 kcal) led to significantly greater elevation of blood glucose levels than the other snacks, which may be unfavorable for cirrhotic patients, who frequently have glucose intolerance. In the 30 cirrhotic patients, supplementation with the BCAA mixture in the late evening significantly improved RQ in the early morning. Carbohydrate-rich meals are used as a late evening snack in cirrhotic patients, but our study indicates that supplementation with a BCAA mixture can also be used to reduce fat oxidation in the early morning, with results similar to those with carbohydrate-rich snacks.


Combination Therapy of Exercise and Angiotensin-Converting Enzyme Inhibitor Markedly Improves Insulin Sensitivities in Hypertensive Patients With Insulin Resistance

The contraction of muscle enhances the release of bradykinin (BK) and improves glucose uptake by the muscle. Angiotensin-converting enzyme inhibitor (ACEI) slows the breakdown of BK, thus the effect of BK is augmented in the presence of ACEI. The present study investigated whether the combination of exercise (increased production of BK) and ACEI (delay in breakdown of BK) might further improve insulin sensitivity in hypertensive patients with insulin resistance (HOMA-R>1.8). Patients were assigned either to increased walking distance (Walking group) or taking 2mg remocapril, an ACEI, daily (ACEI group) for 8 weeks. Then both interventions were given to all patients for 8 weeks (ACEI+Walking group). Blood concentrations of triglycerides were slightly lower in the ACEI+Walking group than at baseline, although there were no significant differences in total cholesterol or high density lipoprotein-cholesterol among the 2 groups. Blood glucose was not significantly different with each treatment, but blood concentrations of insulin and HOMA-R were significantly lower in the Walking and ACEI groups compared with the Control group. The combination of walking and ACEI further lowered blood concentrations of insulin and HOMA-R, which suggests that this treatment is beneficial for hypertensive patients with insulin resistance.


Clinically relevant concentrations of propofol have no effect on adenosine triphosphate-sensitive potassium channels in rat ventricular myocytes.

Activation of adenosine triphosphate-sensitive potassium (K(ATP)) channels produces cardioprotective effects during ischemia. Because propofol is often used in patients who have coronary artery disease undergoing a wide variety of surgical procedures, it is important to evaluate the direct effects of propofol on K(ATP) channel activities in ventricular myocardium during ischemia. The effects of propofol (0.4-60.1 microg/ml) on both sarcolemmal and mitochondrial K(ATP) channel activities were investigated in single, quiescent rat ventricular myocytes. Membrane currents were recorded using cell-attached and inside-out patch clamp configurations. Flavoprotein fluorescence was measured to evaluate mitochondrial oxidation mediated by mitochondrial K(ATP) channels. In the cell-attached configuration, open probability of K(ATP) channels was reduced by propofol in a concentration-dependent manner (EC(50) = 14.2 microg/ml). In the inside-out configurations, propofol inhibited K(ATP) channel activities without changing the single-channel conductance (EC(50) = 11.4 microg/ml). Propofol reduced mitochondrial oxidation in a concentration-dependent manner with an EC(50) of 14.6 microg/ml. Propofol had no effect on the sarcolemmal K(ATP) channel activities in patch clamp configurations and the mitochondrial flavoprotein fluorescence induced by diazoxide at clinically relevant concentrations (< 2 microm), whereas it significantly inhibited both K(ATP) channel activities at very high, nonclinical concentrations (> 5.6 microg/ml; 31 microm).


Autonomic nervous activity before and after eradication of Helicobacter pylori in patients with chronic duodenal ulcer

Helicobacter pylori infection is involved in the formation of chronic peptic ulcer. However, a previously reported hypothesis concerning the involvement of central autonomic nervous disorder in this condition cannot be ruled out. To use spectrum analysis of heart rate viability to examine autonomic nervous activity before and after H. pylori eradication. Twenty patients with chronic duodenal ulcer (duodenal ulcer group) and 20 age-matched normal adults (N group). In both groups, 24-h Holter electrocardiograms (ECGs) were recorded and spectrum analysis of heartrate variability was performed. In the duodenal ulcer group, Holter ECG was recorded before and after H. pylori eradication. In the N group, analysis of heart rate variability showed that high frequency (HF) power, an index of parasympathetic activity, was high at night, while the low frequency (LF)/HF ratio, an index of sympathetic function, was high during the daytime. In the duodenal ulcer group, HF power was higher at night than during the daytime, showing a similar pattern to the N group, but the power value was higher than in the N group (P < 0.05). In the duodenal ulcer group, LF/HF at night was significantly higher than that of the N group. In addition, in the duodenal ulcer group, autonomic activity after H. pylori eradication did not differ significantly from that before H. pylori eradication. In patients with chronic peptic ulcer, both sympatheticotonia and parasympatheticotonia may occur at night, and this abnormality in autonomic nervous activity may cause increased gastric acid secretion and gastric mucosal vasoconstriction. Abnormalities in autonomic activity persist even after H. pylori eradication, suggesting that they may be an independent risk factor in the formation of chronic peptic ulcer in addition to H. pylori infection.


Postprandial hypotension in elderly subjects: spectral analysis of heart rate variability and electrogastrograms


Effect of eicosapentaenoic acid ethyl ester v. oleic acid-rich safflower oil on insulin resistance in type 2 diabetic model rats with hypertriacylglycerolaemia

The purpose of the present study was to test whether hyperlipidaemia and insulin resistance in type 2 diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats can be improved by dietary supplementation with purified eicosapentaenoic acid (EPA) or oleic acid (OA). Male OLETF rats were fed powdered chow (510 g fat/kg) alone (n 8) or chow supplemented with 10 g EPA- (n 8) or OA- (n 8) rich oil/kg per d from 5 weeks until 30 weeks of age. An oral glucose tolerance test and hyperinsulinaemic euglycaemic clamp was performed at 25 and 30 weeks of age. EPA supplementation resulted in significantly (P<0.05) reduced plasma lipids, hepatic triacylglycerols, and abdominal fat deposits, and more efficient in vivo glucose disposal compared with OA supplementation and no supplementation. OA supplementation was associated with significantly increased insulin response to oral glucose compared with EPA supplementation and no supplementation. Inverse correlation was noted between glucose uptake and plasma triacylglycerol levels (r -086, P<0.001) and abdominal fat volume (r -0.80, P<0.001). The result of oral glucose tolerance test study showed that the rats fed EPA tended to improve glucose intolerance, although this was not statistically significant. Levels of plasma insulin at 60 min after glucose was significantly increased in rats fed OA compared with the other two groups. The results indicate that long-term feeding of EPA might be effective in preventing insulin resistance in diabetes-prone rats, at least in part, due to improving hypertriacylglycerolaemia.


トータル·ヘルス·プロモーション·プランによるインスリン抵抗性と最大酸素摂取量への効果


Detection of myocardial damage caused by hepatitis C virus using signal averaged electrocardiogram and I-BMIPP myocardial scintigraphy


Minoxidil-Induced hair growth is mediated by adenosine in cultured dermal papilla cells: possible involvement of sulfonylurea receptor 2B as a target of minoxidil

The mechanism by which minoxidil, an adenosine-triphosphate-sensitive potassium channel opener, induces hypertrichosis remains to be elucidated. Minoxidil has been reported to stimulate the production of vascular endothelial growth factor, a possible promoter of hair growth, in cultured dermal papilla cells. The mechanism of production of vascular endothelial growth factor remains unclear, however. We hypothesize that adenosine serves as a mediator of vascular endothelial growth factor production. Minoxidil-induced increases in levels of intracellular Ca(2+) and vascular endothelial growth factor production in cultured dermal papilla cells were found to be inhibited by 8-sulfophenyl theophylline, a specific antagonist for adenosine receptors, suggesting that dermal papilla cells possess adenosine receptors and sulfonylurea receptors, the latter of which is a well-known target receptor for adenosine-triphosphate-sensitive potassium channel openers. The expression of sulfonylurea receptor 2B and of the adenosine A1, A2A, and A2B receptors was detected in dermal papilla cells by means of reverse transcription polymerase chain reaction analysis. In order to determine which of the adenosine receptor subtypes contribute to minoxidil-induced hair growth, the effects of subtype-specific antagonists for adenosine receptors were investigated. Significant inhibition in increase in intracellular calcium level by minoxidil or adenosine was observed as the result of pretreatment with 8-cyclopentyl-1,3-dipropylxanthine, an antagonist for adenosine A1 receptor, but not by 3,7-dimethyl-1-propargyl-xanthine, an antagonist for adenosine A2 receptor, whereas vascular endothelial growth factor production was blocked by both adenosine A1 and A2 receptor antagonists. These results indicate that the effect of minoxidil is mediated by adenosine, which triggers intracellular signal transduction via both adenosine A1 and A2 receptors, and that the expression of sulfonylurea receptor 2B in dermal papilla cells might play a role in the production of adenosine.

The Journal of Investigative Dermatology


Production of L-defensin-2 by human colonic epithelial cells induced by Salmonella enteritidis flagella filament structural protein

We recently showed that FliC of Salmonella enteritidis increased human beta-defensin-2 (hBD-2) expression, and now describe the signaling responsible pathway. FliC increased the intracellular Ca(2+) concentration ([Ca(2+)](in)) in Caco-2 cells. The [Ca(2+)](in) increase induced by FliC was prevented by U73122 and heparin, but not by chelating extracellular Ca(2+) or pertussis toxin. The FliC-induced increase in hBD-2 promoter activity via nuclear factor kappaB (NF-kappaB) was also inhibited by chelation of intracellular Ca(2+) or by U73122. We conclude that FliC increased [Ca(2+)](in) via inositol 1,4,5-trisphosphate, which was followed by up-regulating hBD-2 mRNA expression via an NF-kappaB-dependent pathway.


Effects of losartan in combination with or without exercise on insulin resistance in Otsuka Long-Evans Tokushima Fatty rats.

Hypertension often complicates type 2 diabetes mellitus, and angiotensin converting enzyme inhibitor treatment has been shown to improve insulin resistance in such cases. However, the effect of angiotensin II type-1 (AT(1)) receptor antagonists on insulin resistance is still controversial. To gain further information on this effect, we examined the effect of losartan on insulin resistance in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model of type 2 diabetes mellitus. Losartan administration alone lowered systolic blood pressure, but did not improve oral glucose tolerance test or insulin resistance in OLETF rats. However, the administration of losartan with exercise significantly improved both systolic blood pressure and insulin resistance relative to control OLETF rats. On the other hand, losartan treatment, regardless of exercise, increased glucose uptake in excised soleus muscle and fat cells. To explore the beneficial effect of losartan on skeletal muscle glucose uptake, we examined intracellular signaling of soleus muscle. Although Akt activity and glucose transporter type 4 (GLUT4) expressions were not affected by losartan with or without exercise, extracellular signal-regulated kinase (ERK1/2) and p38 mitogen-activated protein (MAP) kinase activities were increased by both interventions. These results indicate that angiotensin AT(1) receptor antagonist improved local insulin resistance, but not systemic insulin resistance. These findings may explain the controversy over the effect of angiotensin AT(1) receptor antagonists on insulin resistance in clinical use. The enhancing effect of angiotensin AT(1) receptor antagonist on skeletal muscle glucose uptake may be attributable to MAP kinase activation or other mechanisms rather than phosphatidylinositol 3-kinase activation.


Lidocaine and mexiletine inhibit mitochondrial oxidation in rat ventricular myocytes.

Accumulating evidence suggests that mitochondrial rather than sarcolemmal adenosine triphosphate-sensitive K+ (K(ATP)) channels may have an important role in the protection of myocardium during ischemia. Because both lidocaine and mexiletine are frequently used antiarrhythmic drugs during myocardial ischemia, it is important to investigate whether they affect mitochondrial K(ATP) channel activities. Male Wistar rats were anesthetized with ether. Single, quiescent ventricular myocytes were dispersed enzymatically. The authors measured flavoprotein fluorescence to evaluate mitochondrial redox state. Lidocaine or mexiletine was applied after administration of diazoxide (25 microM), a selective mitochondrial K(ATP) channel opener. The redox signal was normalized to the baseline flavoprotein fluorescence obtained during exposure to 2,4-dinitrophenol, a protonophore that uncouples respiration from ATP synthesis and collapses the mitochondrial potential. Diazoxide-induced oxidation of flavoproteins and the redox changes were inhibited by 5-hydroxydecanoic acid, a selective mitochondrial K(ATP) channel blocker, suggesting that flavoprotein fluorescence can be used as an index of mitochondrial oxidation mediated by mitochondrial K(ATP) channels. Lidocaine (10(-3) to 10 mM) and mexiletine (10(-3) to 10 mM) reduced oxidation of the mitochondrial matrix in a dose-dependent manner with an EC50 of 98+/-63 microM for lidocaine and 107+/-89 microM for mexiletine. Both lidocaine and mexiletine reduced flavoprotein fluorescence induced by diazoxide in rat ventricular myocytes, indicating that these antiarrhythmic drugs may produce impairment of mitochondrial oxidation mediated by mitochondrial K(ATP) channels.


Relationship among gastric motility,autonomic activity,and portal hemodynamics in patients with liver cirrhosis

We examined the effects of the autonomic nervous function and the volume of portal blood flow to clarify the mechanism of the abnormal gastric motility in patients with liver cirrhosis. Heart rate variability, electrogastrogram (EGG), and volume of portal blood flow were measured before and after a meal in 27 patients with liver cirrhosis (LC group) and in 20 normal subjects (N group). Autonomic nervous function was evaluated by using spectral analysis of heart rate variability. We used the cine phase-contrast (PC) method, using magnetic resonance imaging (MRI) to measure the portal flow, while the peak frequency and spectral power of the EGG were measured at pre- and postprandial change. The ratio of low frequency power to high frequency power (LF/HF) was significantly higher, and the HF power was significantly lower in the LC group than in the N group both before and after a meal. In both groups, the electrogastrographic peak power ratio before and after a meal showed a positive correlation with the HF ratio, and an inverse correlation with the LF/HF ratio. In addition, portal blood flow volume was significantly decreased in the LC group than in the N group. However, the increased rate of portal blood flow after a meal correlated positively with the increased rate of electrogastrographic peak power. Moreover, gastric motility was positively correlated with esophageal varices and coma scale with the use of multivariate analysis. Parasympathetic hypofunction, sympathetic hyperfunction and portal hemodynamics were closely related with gastric motility in cirrhotic patients. In addition, gastric motility was decreased, at least in part, by the ingestion of food in cirrhotic patients because of abnormalities in autonomic functions and portal blood flow following a meal.

Journal of Gastroenterology and Hepatology


Imparied retension of technetium-99m tetrofosmin in hypertrophic cardiomyopathy.


32チャンネル高温超伝導量子干渉計を用いた心起電力の可視化

32チャンネル高温超伝導量子干渉計を用いた心起電力の可視化

The Journal of Japan Biomagnetism and Bioelectromagnetics Society


摂食による冠動脈血流速度の変化，胃電図および冠動脈シネMRAを用いた検討

摂食による冠動脈血流速度の変化，胃電図および冠動脈シネMRAを用いた検討


心房細動治療に関するアンケート調査 ‐徳島県と全国の比較‐

心房細動治療に関するアンケート調査 ‐徳島県と全国の比較‐


Autonomic nervous function in patients with peptic ulcer studied by spectral analysis of the heart rate variability

This study is intended to clarify the relationship between occurrence of peptic ulcer disease and dysfunction of the autonomic nervous system. We studied heart rate variability and assessed the circadian rhythm of autonomic nervous function in 20 patients with peptic ulcer (PU group) and 20 age-matched healthy controls (N group) using 24-hour Holter monitoring. Moreover, the relationship between gastric juice secretion and autonomic activity was examined under intravenous injection of insulin or butylscopolamine in adult mongrel dogs. High frequency spectral (HF) power, an indicator of parasympathetic tone, was increased markedly at night in the PU group. Low frequency spectral (LF) power, an indicator of sympathetic tone modified by vagal tone, was higher during the day than at night in the N group, whereas this normal circadian rhythm of LF power disappeared in 11 cases (55%) in the PU group. In addition, the LF power was increased significantly at night (p<0.01) in the PU group. HF power and gastric juice secretion was increased by the administration of insulin. High sympatho-vagal tone at night may result in spasm of gastric arteries and excess secretion of gastric acid in the PU group. These results suggest that the nocturnal acceleration of LF, HF, and LF/HF is related to peptic ulcer diseases.


Clinical application of QT dispersion on ventricular hypertrophy using magnetocardiogram


Current sources of initial QRS forces in left ventricular hypertrophy,WPW syndrome,and left bundle branch brock - origin of septal vector


Evaluation of the total health promotion plan in japan,as related to health promotion effects and the prevention of lifestyle-related diseases

The present study was undertaken to investigate whether health-promoting activities in Japan are useful for preventing the development of lifestyle-related diseases and for promoting health. One thousand, one hundred and sixty-seven Japanese workers were given a medical health check and had their maximum oxygen uptake measured according to the total health promotion plan (THP) protocol, which the Japanese Ministry of Health, Labor and Welfare is actively planning. Correlations between the maximum oxygen uptake and performance on health check items were statistically evaluated. The maximum oxygen uptake was positively correlated with the duration of a worker's ability to stand on one leg, and on the frequency with which they performed upper body weight lifting. In addition, the maximum oxygen uptake was negatively correlated with age, body weight, thickness of subcutaneous fat in the upper arms and shoulders, body fat ratios, body mass index (BMI), maximum and minimum blood pressures, resting heart rates, and total cholesterol levels. Moreover, the maximum oxygen uptake tended to be significantly higher in both male and female subjects who exercised regularly. It is suggested that maximum oxygen uptake and regular exercising play important roles in the inhibition of risk factors for ischemic heart diseases. Therefore, we believe the THP can play an important role in the primary prevention of lifestyle-related diseases. The purpose of the THP in Japan is to promote the achievement of healthy lifestyles in individual subjects, both from mental and physical perspectives. These results suggest that such efforts may help prevent the development of lifestyle-related diseases.


99mTc-MIBIによる運動負荷時冠血流増加率と冠動脈血流速波形との関連 --- -冠動脈MR coronary angiographyを用いた検討-


Stress and coping behavior in patients with diabetes mellitus.

Diabetes mellitus is a disease which must be controlled over the lifetime of a patient. We investigated the issues of stress and coping for diabetes mellitus which may influence self-management. In addition, we examined the association of these factors with blood glucose control, in order to review self-management instructions for diabetes mellitus. The study included 153 patients with diabetes mellitus. The patients were divided into two subgroups: good-control group, comprising patients with glycohemoglobin (HbA1c) values less than 7.0%; and poor-control group, comprising those with HbA1c values of 7.0% or more. All patients responded to a questionnaire regarding stress tolerance, Jalowiec and Power's coping scale and awareness of diabetes mellitus. Stress tolerance was not significantly different between the good-control and poor-control groups. No significant gender differences in coping score were evident for the good-control group. However, in the poor-control group, the coping score in men was significant higher than that in women. The problem-oriented coping score for men in the poor-control group was significantly higher than that for the good-control group (p < 0.01). In a comparison of awareness of diabetes mellitus, the proportion of patients who replied that they were rigidly following diabetes treatment was higher in the poor-control group than the good-control group. Patients with diabetes mellitus may have a knowledge of the disease and a strong will to resolve problems. This is especially true for male patients in that their will appeared to be stronger, but they may not have the resolve to establish appropriate behavior patterns. In the future, methods for evaluating self-management should be included in diabetes education.


Evaluation of autonomic nervous function during upper gastrointestinal endoscopy using heart rate variability

To investigate autonomic nervous function during upper gastrointestinal endoscopy, we analyzed R-R interval variability from electrocardiograms obtained during endoscopy. Holter electrocardiogram recordings were made before and after premedication, and during endoscopy. Time- and frequency-domain analyses of heart rate variability were performed in 54 subjects premedicated with scopolamine butylbromide (SB group) and in 66 subjects premedicated with glucagon (G group). To determine the effect of autonomic imbalance on arrhythmia generation during endoscopy, subjects with arrhythmias (A group) were compared with subjects without arrhythmias (N group). In the SB group, high frequency spectral power (HF power; 0.15 to 0.40 Hz), which reflects parasympathetic activity, decreased significantly after premedication, and decreased further during endoscopy (P < 0.01). Moreover, HF power before premedication or during endoscopy in the A group was significantly lower than that in the N group (P < 0.01). This study suggests that the measurement of HF power prior to endoscopy can identify subjects with reduced HF power. This should allow the prevention of cardiovascular complications related to premedication and endoscope insertion.


Changes in autonomic nervous activity during colonoscopy using spectral analysis heart rate variability.


Is autonomic dysfunction a necessary condition for chronic peptic ulcer formation ?

The relationship between 1/f fluctuation of the heart rate variability and Helicobacter pylori infection was evaluated, in order to clarify whether autonomic nervous dysfunction is a necessary condition for chronic peptic ulcer formation. The subjects were 11 patients with recurrent chronic peptic ulcer and 20 age-matched normal subjects. Holter ECGs were recorded over 24 h, and the 1/f(-x) fluctuation of the heart rate was computed. The 1/f(-x) fluctuation of the heart rate is a novel index of autonomic function that has been shown to reflect a patient's pleasant mood. For 1/f(-x) fluctuation, the slope of the regression line (-x) was determined and cosine fitting of the absolute slope of the regression line over a 24-h period was performed. For the normal group, the absolute slope of the regression line during daytime and night-time were 0.53 +/- 0.16 and 1.05 +/- 0.18, respectively. For the peptic ulcer group, the corresponding values during daytime and night-time were 0.94 +/- 0.15 and 1.84 +/- 0.18, respectively. The mean value of the cosine curve was 0.76 +/- 0.23 in the normal group and 1.12 +/- 0.25 in the peptic ulcer group. Thus, these values were significantly higher for the latter group than for the former group (P<0.05). No statistically significant difference in H. pylori infection between the two groups was observed. Autonomic nervous dysfunction as well as H. pylori infection appears to be a necessary condition for chronic peptic ulcer formation.


Blockade of adenosine triphosphate-sensitive potassium channels by thiamylal in rat ventricular myocytes.

The adenosine triphosphate (ATP)-sensitive potassium (KATP) channels protect myocytes during ischemia and reperfusion. This study investigated the effects of thiamylal on the activities of KATP channels in isolated rat ventricular myocytes during simulated ischemia. Male Wistar rats were anesthetized with ether. Single, quiescent ventricular myocytes were dispersed enzymatically. Membrane currents were recorded using patch-clamp techniques. In the cell-attached configuration, KATP channel currents were assessed before and during activation of these channels by 2,4-dinitrophenol and after administration of 25, 50, and 100 mg/l thiamylal. The open probability was determined from current-amplitude histograms. In the inside-out configuration, the current-voltage relation was obtained before and after the application of thiamylal (50 mg/1). In the cell-attached configuration, 2,4-dinitrophenol caused frequent channel opening. 2,4-Dinitrophenol-induced channel activities were reduced significantly by glibenclamide, suggesting that the channels studied were KATP channels. Open probability of KATP channels was reduced by thiamylal in a concentration-dependent manner. KATP channels could be activated in the inside-out configuration because of the absence of ATP. Thiamylal inhibited KATP channel activity without changing the single-channel conductance. The results obtained in this study indicate that thiamylal inhibits KATP channel activities in cell-attached and inside-out patches, suggesting a direct action of this drug on these channels.


Indution of inducible nitric oxide synthanse by ginsenosides in cultured porcine endothelial cells


Magnetic Resonance Coronary Angiography in Patients with Ischemic Heart Disease Analysis of Coronary Arterial Blood Flow Velocity Pattern

Only a few reports evaluating coronary arterial blood flow velocity patterns using magnetic resonance (MR) coronary angiography have appeared to date. This study reports an evaluation of coronary arterial blood flow velocity patterns in patients with ischemic heart disease and in healthy subjects using MR coronary angiography. The subjects consisted of 20 patients with ischemic heart disease (IHD group) and 20 normal healthy subjects (N group). Using the fCARD PC method, ECG-gated MR coronary angiography was performed using an anteroposterior opposing phased array coil. Regions of interest were placed on bilateral coronary arteries to measure coronary arterial blood flow velocity patterns. The IHD group was divided into two subgroups, based on the presence (MI group) or absence (AP group) of infarcted myocardium using 99m Tc-methoxyisobutylisonitrile (MIBI) myocardial scintigraphy. Average diastolic peak velocity (ADPV) was lower in the IHD group than in the N group. In addition, the diastolic / systolic velocity ratio (DSVR) was significantly lower in the MI group. Moreover, in the AP group, both the ADPV and DSVR values were significantly increased in those who had undergone percutaneous transluminal coronary angioplasty postoperatively. Different from the Doppler guidewire method, MR coronary angiography facilitates noninvasive evaluation of coronary arterial blood flow velocity. Therefore, these results indicate that MR coronary angiography represents a potentially useful technique for diagnosing lesions of coronary arteries and evaluating their functions. This noninvasive method can be expected to replace the invasive Doppler guidewire method in the near future with development of MR coronary angiography technology.


Early diagnosis of interferon-induced myocardial disorder in patients with chronic hepatitis C : evaluation by myocardial imaging with123I-BMIPP

Interferon (IFN) therapy for chronic hepatitis C is sometimes associated with cardiac complications. In the present study, we performed myocardial imaging with 123I-labeled beta-methyl-p-iodophenylpentadecanoic acid (123I-BMIPP) in order to evaluate myocardial disorders caused by IFN. We studied 40 healthy subjects (H group) and 25 patients with chronic hepatitis C who had been treated with IFN (IFN group). A Holter electrocardiogram (ECG) was performed and the autonomic nervous function was assessed by analyzing the spectral variability and 1/f fluctuation of heart rate. Myocardial planner imaging with 123I-BMIPP was performed to obtain the time activity curve for 20min immediately after administration of 123I-BMIPP (dynamic study). Early and delayed myocardial single photon emission computed tomography (SPECT) images were expressed as Bull's eyes and the myocardium was divided into four segments to calculate the washout rate for each segment on early and late SPECT images (early and late SPECT study). No significant differences in autonomic nervous function were observed between the two groups in heart rate variability. In a dynamic study, the reduction rate from the time activity curve was significantly higher in the IFN group compared with the H group (reduction rate, IFN group, 5.3 +/- 3.7% vs H group, 1.2 +/- 3.3%; P < 0.05). In the early and delayed myocardial SPECT study, the washout rate for the IFN group was significantly increased in all myocardial areas compared to that in the H group. However, the metabolic disorder of fatty acids caused by IFN was reversed on the second 123I-BMIPP myocardial scintigraphy examination several months after IFN therapy. These results indicate that metabolic disorders of fatty acids caused by IFN therapy can be detected before abnormalities are observed by Holter-ECG or echocardiography.


Evaluation of autonomic nervous function in patients with essential hypertension complicated with peptic ulcer

Journal of Gastroenterology and Hepatology


Age-related changes in the magnitude of ventricular depolarization vector : analyses by magnetocardiogram

The magnetocardiogram has the beneficial feature that permits the strength and location of the current dipole to be estimated. This study examines the issue of whether the magnitude of the heart current during depolarization phase was influenced by the age of healthy subjects. The magnetocardiograms were recorded by means of a second-derivative SQUID (superconducting quantum interference device) magnetometer (BT Corp, Model BMP, San Diego, CA) in 150 healthy subjects. The subjects were subgrouped into 5 age-based categories according to the age. The current dipole of the maximum QRS complex was determined from isofield contour maps during the ventricular depolarization phase, and no significant differences were observed in the magnitude in the current source for any age category. However, the amplitudes of the RV5 and SV1 + RV5 in the standard electrocardiogram were larger in 65 to 74-year-old women than other age groups, and the SV1 + RV5 was smaller for the 45 to 74-year-old men than for the men aged 25 to 44 years. These findings suggest that the age-associated changes in the QRS complex observed by the electrocardiogram are caused by increased electric resistance and not by the heart current itself. The results additionally suggest that no effects of aging were observed in the actual heart current of the heart during the depolarization phase.


老年者における上部消化管内視鏡検査中の自律神経活動およびQTc dispersionの変動


高齢者における食事負荷による血圧変動の成因 ー心拍変動解析および胃電図における検討ー


心磁図法を用いた心臓異常所見の検出:心電図法で捉えられない心起電力を検出できるか

The Journal of Japan Biomagnetism and Bioelectromagnetics Society


高齢者における食後低血圧の成因 --- 自律神経活動および胃運動との関連性について

日本高齢者消化器医学会議会誌

日本高齢者消化器医学会議会誌


Evaluation of Cardiac Function in Myocardial Infarction Patients by ECG 99mTc-MIBI Gated SPECT Using a Three-dimensional Perfusion/Motion Map Procedure

Three-dimensional (3D) radionuclear myocardial imaging has improved the evaluation of left ventricular wall motion. However, there have been no studies evaluating left ventricular function using 3D-perfusion/motion map techniques. We hypothesized that the 3D-perfusion/motion map could accurately evaluate left ventricular wall motion even in patients with a history of myocardial infarction. Electrocardiogram (ECG)-gated single photon emission computed tomography (SPECT) using 99mTc-methoxy isobutyl isonitrile (MIBI) was performed in 20 patients with a history of myocardial infarction who underwent left ventriculography. Myocardial imaging data were collected during ECG-gated SPECT using a 3-headed gamma camera. Reconstructed 3D SPECT images were oriented to correspond to standard left ventriculography views (right anterior oblique and left anterior oblique projections), and the shortening fraction (SF) was calculated using the center line method. The SF and left ventricular ejection fraction from 3D SPECT images were compared with those determined by left ventriculography. There was a significant correlation between left ventriculography and the 3D-perfusion/motion map procedure in determining SF for all regions of the left ventricle except the anterobasal and posterior segments by using the Bland and Altman method. The 3D-perfusion/motion map procedure offers the advantage that the influences of contraction-related myocardial torsion and three-dimensional compression are minimized. In addition, this method facilitates evaluation of images from nonstandard projections. We conclude that this method may be useful for evaluating left ventricular function.


Age-related endothelium-dependent vascular relazation in rat thoracic aorta in response to colforsin

Colforsin, a novel water-soluble forskolin derivative, increases intracellular cyclic AMP by direct stimulation of adenylate cyclase and has strong positive inotropic and vasodilative effects. However, it is not known whether colforsin causes nitric oxide (NO) release and enhances endothelium-dependent vascular relaxation. We studied NO production and relaxation on exposure to colforsin in thoracic aorta from rats aged 4, 12 and 60 weeks. When a low concentration of colforsin was added to a solution bathing ring segments of aorta from 12-week-old rats, relaxation was greater in the ring segments with intact endothelium than in those from which the endothelium had been removed. A high concentration of colforsin induced the same degree of relaxation of ring segments with or without endothelium, probably by a direct effect on vascular smooth muscle cells. Production of NO in response to colforsin by cultured endothelial cells from 12-week-old rat aorta was demonstrated by the electron paramagnetic resonance spin trapping method. A low concentration of colforsin relaxed aortic segments with intact endothelium from 4-week-old rats more than those from 12-week-old or 60-week-old rats. Reversal of relaxation by NG-nitro L-arginine, an NO synthesis inhibitor, was most significant in arteries from 4-week-old rats. Production of NO after exposure to colforsin was greater in aortic segments from 4-week-old rats than older rats, as detected by an NO-selective electrode. Colforsin induces vasodilation in part by releasing NO from the endothelium in rat thoracic aorta. In addition to a direct vasodilative effect on the vascular smooth muscle cells, an endothelium-dependent vasodilative effect is also important in younger arteries.


QT dispersionの臨床的意義:心臓磁界を用いた左室肥大における検討

QT dispersionの臨床的意義:心臓磁界を用いた左室肥大における検討


Respiratory Quotient in Patients with Non-Insulin-Dependent Diabetes mellitus Treated with Insulin and Oral Hypoglycemic Agents

The respiratory quotient (RQ) reflects the amount of energy derived from carbohydrate as apposed to fat metabolism. To assess the metabolic state of patients with non-insulin-dependent diabetes mellitus, the RQ was measured five times a day (at 09.00, 11.00, 13. 00, 14.00, and 17.00 h) in 20 healthy subjects and 60 diabetic patients. Diabetic patients treated with insulin or sulfonylurea showed significantly higher RQ values than normal subjects and nontreated diabetic patients. Diabetic patients without treatment showed higher glucose levels, and their RQ values were significantly lower than those of treated patients. There was a significant inverse correlation between RQ and blood glucose levels at 11.00 h (r = -0.361, p < 0.01) in diabetic patients, but no significant relation with HbA1c. Treated diabetic patients with a higher body mass index tended to show a higher RQ than those with a lower one (r = -0.269, p = 0.083). Within 1 year, 7 of 13 patients, who had RQ > 1.0, gained more than 3 kg, while only 5 of the remaining 32 treated diabetic patients gained more than 3 kg (p < 0.05). This demonstrates that diabetic patients with a higher RQ tended to gain weight despite the use of insulin or oral hypoglycemia agents. The RQ increased by infusing both insulin and glucose in normal subjects. These results suggest that a high RQ results from excess insulin and excess food. The RQ is a good predictor of weight gain in diabetic patients treated with either insulin or oral hypoglycemic agents.


Mismatch between myocardial accumulation of 123I-MIBG and 99mTc-MIBI and late ventricular potentials in patients after myocardial infarction : Association with the development of ventricular arrhythmias

Late ventricular potentials are widely used to predict life-threatening arrhythmias, although the predictive value is low. To improve prediction, we correlated the incidence of ventricular arrhythmias with mismatches in myocardial 99mTc-methoxyisobutylisonitrile (MIBI)/(123)I-metaiodobenzylguanidine (MIBG) accumulation and late ventricular potentials (LP). Fifty patients with old myocardial infarctions were divided into an LP-positive group (n = 19) and an LP-negative group (n = 31). On bull's-eye single photon emission computed tomographic MIBI and MIBG images, the heart was divided into 9 segments to evaluate the accumulation of the 2 nuclides. There was no difference in total defect score (TDS) for MIBI between the LP-positive and LP-negative groups. However, TDS for MIBG and differences TDS between MIBI and MIBG (ATDS) were significantly greater in the LP-positive group. The incidence of severe ventricular arrhythmias was greater among patients with an increased ATDS in the LP-positive group. Thus the combination of these two methods may improve the prediction of ventricular arrhythmias after myocardial infarction.


Does prolonged exercise alter diet-induced thermogenesis?

Diet-induced thermogenesis (DIT) is mainly an insulin-mediated response and the result of fat and glycogen synthesis. We investigated DIT at rest and after exercise to clarify the mechanism of exercise-induced changes in DIT in 6 healthy men (mean age 36 +/- 16 years). Subjects exercised for 1 h at 58% of maximal O2 consumption on a bicycle ergometer and then rested for 8 h sitting in a comfortable chair (exercise experiment). On a different day, subjects rested for 8 h without preceding exercising (non-exercise experiment). At 12.30 h, the subjects were given their second meal. DIT to individual meal did not differ significantly between the exercise and non-exercise days. Increased insulin sensitivity and increased free fatty acid oxidation by exercise may facilitate the conversion of glucose to glycogen in muscle. On the other hand, insulin secretion expressed as the ratio of plasma levels of insulin to glucose after the meal was significantly decreased in the exercise experiment (p < 0.05). Study of heart rate variability showed that sympathetic tone, a primary hormonal determinant of glucose metabolism during exercise, was increased and parasympathetic tone was decreased during the recovery period in the exercise experiment (p < 0.05). These findings suggest that changes in DIT are affected by many factors and may be related to the balance between these counteracting factors.


Assessment of autonomic nervous activity during gastrointestinal endoscopy --- Analysis of blood pressure variability by tonometry

Journal of Gastroenterology and Hepatology


Brugada syndrome associated with an autonomic disorder


Endothelium-derived hyperpolarizing factor activates Ca2+activated K+channels in porcine coronary artery smooth muscle cells

Although endothelium-derived hyperpolarizing factor (EDHF) activity has been demonstrated in arteries from various species, EDHF has not been chemically identified, nor its mechanism of action characterized. To elucidate this mechanism, we tested the effect of EDHF on large-conductance Ca2+-activated K+ (K(Ca)) channels in porcine coronary artery smooth muscle cells. By using a patch-clamp technique, single-channel currents were recorded in cultured smooth muscle cells; the organ bath also contained a strip of porcine coronary with endothelium, which served as the source of endothelium-derived relaxing factor(s) including EDHF. Exposure of endothelium to 10(-6) M bradykinin activated K(Ca) channels in cultured smooth muscle cells in cell-attached patches. When the experiment was performed in the presence of 10 microM indomethacin and 30 microM N(G)-nitro-L-arginine (L-NNA), which block the generation of prostaglandin I2 (PGI2) and NO, respectively, K(Ca) channel activity was stimulated by bradykinin, indicating the direct involvement of EDHF in K(Ca) channel stimulation. Neither 10 microM methylene blue nor 25 microM Rp-cAMPS inhibited bradykinin-induced K(Ca) channel activity. In inside-out patches, the addition of bradykinin to the solution was without effect on K(Ca) channel activation. However, in the presence of 0.5 mM guanosine triphosphate (GTP) and 1.0 mM adenosine triphosphate (ATP) in the bath solution, K(Ca) channels was activated by bradykinin. In outside-out patches, the addition of bradykinin also increased K(Ca) channel activity, when GTP and ATP were added to the pipette solution. The addition of GDP-beta-S (100 microM) in the cytosolic solution completely blocked the activation K(Ca) channels induced by bradykinin in inside-out and outside-out patches. Pretreatment with 30 microM quinacrine, a phospholipase A2 inhibitor, or 3 microM 17-octadecynoic acid (17-ODYA), a cytochrome P450 inhibitor, in addition to indomethacin and L-NNA, abolished bradykinin-stimulated K(Ca) channel activity in cell-attached patches. Both 14,15-epoxyeicosatrienoic acid (EET) and 11,12-EET increased the open probabilities of K(Ca) channels in cell-attached patches. These results suggest that EDHF, released from endothelial cells in response to bradykinin, hyperpolarizes smooth muscle cells by opening K(Ca) channels. Furthermore, our data suggest that EDHF is an endothelium-derived cytochrome P450 metabolite of arachidonic acid. The effect of EDHF on K(Ca) channels is not associated with an increase of cAMP and cGMP. The activation of K(Ca) channels appears to be due to the activation of GTP-binding protein.


Cerebrospinal ascites developed 3 years after ventriculoperitoneal shunting in a hydrocephalic patient.

We report a 23-year-old woman who developed ascites 3 years after ventriculoperitoneal shunting. Revision of the shunt to ventricular drainage followed by ventriculo-atrial shunting was required for resolution of ascites. In our patient the pathophysiology of this rare shunt complication most likely involved impaired absorption of fluid within the peritoneum associated with multiple shunt reconstructions and tube extensions resulting in chronic inflammation. Cerebrospinal ascites must be suspected irrespective of post-shunt intervals in similar patients.


Effect of acidosis on Ca2+-activatecd K+ channels in cultured porcine coronary artery smooth muscle cells

Pflügers Archiv : European Journal of Physiology


Bradykinin directly triggers GLUT4 translocation via an insulin-independent pathway.

Physical exercise induces translocation of GLUT4 from an intracellular pool to the cell surface in skeletal muscles and increases glucose uptake via an insulin-independent pathway. However, the molecular mechanism remains to be identified. Some studies have suggested that bradykinin is locally released from contracting muscles and may be responsible for GLUT4 translocation and the increase of glucose transport in skeletal muscles. To determine whether bradykinin directly triggers GLUT4 translocation, we established L6 myotubes, 3T3-L1 adipocytes, and Chinese hamster ovary cells stably expressing c-myc epitope-tagged GLUT4 (GLUT4myc) and bradykinin B2 receptors. We found that bradykinin directly triggered GLUT4myc translocation and increased the rate of glucose uptake in a dose-dependent manner in these cells. The translocation with bradykinin occurred even after pretreatment with an islet-activating protein, wortmannin, and phorbol 12,13-dibutyrate. The signaling pathway does not seem to be mediated by Gi, phosphatidylinositol 3-kinase, or protein kinase C. It is insulin-independent and via trimeric G-protein Gq. Bradykinin is probably one of the factors responsible for exercise-stimulated glucose uptake in skeletal muscles.


Lactate-induced vascular relaxation in porcine coronary arteries is mediated by Ca2+activated K+ channels

Under ischemic conditions and during strenuous exercise, lactate concentrations increase in coronary artery smooth muscle cells. Although lactate causes pH-independent vasorelaxation, the mechanisms responsible for this effect are unclear. We investigated the effect of lactate on K+ channels in smooth muscle cells from porcine coronary arteries. Neutralized lactate (3-100 mm) induced vasorelaxation in ring segments of porcine coronary arteries precontracted with KCl in a dose-dependent manner. One millimolar tetraethylammonium (TEA), an inhibitor of Ca2+-activated K+ channels (KCa channels), reversed the lactate-induced relaxation, while 60 microM glibenclamide, an inhibitor of ATP-sensitive K+ channels (KATP channels), did not. In both inside-out and cell-attached patch clamp technique with cultured smooth muscle cells, the KCa channels were activated by lactate. In inside-out patches, lactate activated KCa channels, even under acidic conditions. This is in contrast to the effect of H+ which inactivated KCa channels. We conclude that vasodilation of porcine coronary arteries induced by lactate is, at least in part, mediated by activation of KCa channels. This effect may be self-protective by maintaining coronary blood flow during ischemia.

Journal of Molecular and Cellular Cardiology


Hydrogen peroxide-induced vascular relaxtion in porcine coronary arteries is mediated by Ca2+-activated K+ channels


心磁界から求めた心室脱分極ベクトルの加齢変化

心磁界から求めた心室脱分極ベクトルの加齢変化

The Journal of Japan Biomagnetism and Bioelectromagnetics Society


The Official Journal of Japanese Society of Laboratory Medicine


呼気ガス分析による糖尿病治療の評価

呼気ガス分析による糖尿病治療の評価


Dihydropridine系Ca拮抗薬の心臓交感神経機能への影響

Dihydropridine系Ca拮抗薬の心臓交感神経機能への影響


Coronary-Pulmonary Artery Fistulae Depicted by Multiplanar Reconstruction Using Magnetic Resonance Imaging


Effects of intravenous administration of L-arginine on autonomic nervous activities: Analysis of heart rate variability


Effects of cytosolic ATP and other nucleotides on Ca2+-activated K+ channels in cultures bovine adrenal chromaffin cells.


Human chymase, an enzyme forming novel bioactive 31-amino acid length endothelins.


Ischaemic electrocardiographic changes after massive blood transfusion : Findings based on myocardial scintigraphy using 99mTc-MIBI and 123I-MIBG

We performed myocardial scintigraphy on a patient with ischaemic electrocardiographic changes after massive blood transfusion. Although there was no defect by 99mTc-MIBI scintigraphy, 123I-MIBG scintigraphy was observed suggesting denervation after massive blood transfusion. Myocardial scintigraphy using 99mTc-MIBI or 123I-MIBG can be useful for the evaluation of myocardial dysfunction with reversible myocardial infarction.


Autonomic nervous system activity during infusion of L-arginine in patients with liver cirrhosis


心磁図法によるQTc dispersion:心筋梗塞による検討

心磁図法によるQTc dispersion:心筋梗塞による検討


心磁界計測による心起電力の発生機序の検討‐左室肥大例における初期ベクトル

心磁界計測による心起電力の発生機序の検討‐左室肥大例における初期ベクトル


Signal averaged electrocardiogram after exercise in patients with mitral valve prolapse

While late potentials are correlated with an increased incidence of ventricular tachycardia, they are not necessarily a good predictor of ventricular electrical instability in patients with mitral valve prolapse (MVP). Our objective was to determine whether the signal averaged electrocardiogram (SAECG) after exercise can discriminate groups with a higher frequency of ventricular arrhythmia from those without. The SAECG was recorded before and after treadmill exercise in 20 normal subjects (N group), 20 patients with MVP (MVP group) and 10 patients with old myocardial infarction (MI group). Five patients (25%) in the MVP group and two patients (33%) in the MI group had late potentials before exercise. Late potentials in the MI group did not disappear with exercise, whereas they disappeared with exercise in two patients in the MVP group. The results suggest that the late potentials observed in patients with MVP differ in nature from those with old myocardial infarction and are not always related to lethal arrhythmia.


Evaluation of Myocardial Sympathetic Nerve Function in Patients With Mitral Valve Prolapse Using Iodine-123-Metaiodobenzylguanidine Myocardial Scintigraphy

123I-Metaiodobenzylguanidine心筋シンチグラフィーによる僧帽弁逸脱の交感神経機能評価


INTRACELLULAR AND EXTRACELLULAR Ca2+REGULATE HISTAMINE-INDUCED RELEASE OF NITRIC OXIDE IN VASCULAR ENDOTHELIAL CELLS AS SHOWN WITH SENSITIVE AND SELECTIVE NITRIC OXIDE ELECTRODES


A 90-year old patient with atrial septal defect and sinus rhythm

A 90-year old patient with an atrial septal defect (ASD) and sinus rhythm, but no history of atrial fibrillation of heart failure is presented. Literature searches revealed no similar report of such a case. In addition, this patient represents the oldest documented patients with ASD associated and sinus rhythm.


心磁図法による心筋梗塞症の心起電力の検討

心磁図法による心筋梗塞症の心起電力の検討

心電図 : 日本心電学会誌


64チャンネル磁束計を用いた小腸磁界の測定

64チャンネル磁束計を用いた小腸磁界の測定


特発性心筋症における初期QRSベクトルの信号源

特発性心筋症における初期QRSベクトルの信号源


L-アルギニン静脈注射による自律神経活動の影響:心拍変動解析による検討

L-アルギニン静脈注射による自律神経活動の影響:心拍変動解析による検討


長時間運動負荷後の回復過程のエネルギー代謝と自律神経活動の検討‐呼気ガス分析と心拍変動解析による検討


Heart rate variability during painful medical procedures(Percutaneous ethanol injection therapy)

Electrocardiology '96 from the cell to the body surface


摘出ラット大動脈に対するアムリノンの内皮依存性血管弛緩作用と加齢による影響

摘出ラット大動脈に対するアムリノンの内皮依存性血管弛緩作用と加齢による影響


摘出ブタ大動脈でのアムリノンによる一酸化窒素(NO)産生の測定

摘出ブタ大動脈でのアムリノンによる一酸化窒素(NO)産生の測定


Protein kinase c-independent inhibition of the Ca2+-activated K+ channel by angiotensin II and endothelin-1

We previously reported that the Ca(2+)-activated K+ channel (KCa-channel) in cultured smooth muscle cells from porcine coronary artery was inhibited by protein kinase C (C-kinase). In this study, inhibition of the KCa-channel by receptor-mediated vascular contractile agonists, such as angiotensin II (ANG II) and endothelin-1 (ET-1), was investigated by the patch-clamp technique. In cell-attached patches, addition of ANG II (500 nM) or ET-1 (50 nM) to the bath inhibited the KCa-channel activated by the calcium ionophore A23187 (10-20 microM). Phorbol 12-myristate 13-acetate (PMA, 1 microM), a C-kinase activator, also decreased the open probability of the KCa-channel. The PMA-induced decrease in the open probability was reversed by subsequent application of staurosporine (1 nM), a C-kinase inhibitor, but the ANG II- and ET-1-induced decreases were not reversed by subsequent application of staurosporine (> 30 nM). Pretreatment of smooth muscle cells with 30 nM staurosporine, a protein kinase inhibitor, or 1 mM neomycin, an inhibitor of phospholipase C, also did not abolish the inhibition of the KCa-channel by ANG II. Furthermore, ANG II inhibited the KCa-channel in cells in which C-kinase was down-regulated. These results indicate that, in porcine coronary artery smooth muscle cells, ANG II and ET-1 inhibit the KCa-channel by a C-kinase-independent mechanism.


MCI-154 activates the Ca2+-activated K+ channel of vascular smooth muscle cells


僧帽弁逸脱における運動負荷時の心拍変動スペクトルの検討

僧帽弁逸脱における運動負荷時の心拍変動スペクトルの検討


64チャンネルSQUID磁束計を用いた胃活動電流の測定‐臨床的有用性の検討‐

64チャンネルSQUID磁束計を用いた胃活動電流の測定‐臨床的有用性の検討‐

The Journal of Japan Biomagnetism and Bioelectromagnetics Society


高温超伝導SQUIDを用いた胃運動機能の評価

高温超伝導SQUIDを用いた胃運動機能の評価


前壁心筋梗塞症および健常例の初期QRSベクトルの信号源推定

前壁心筋梗塞症および健常例の初期QRSベクトルの信号源推定


Nonendothelial-derived nitric oxide activates the K+ channels in cultured vascular smooth muscle cells


僧帽弁逸脱における血中遊離型および硫酸抱合型カテコールアミンの変動

僧帽弁逸脱における血中遊離型および硫酸抱合型カテコールアミンの変動


Noninvasive localization of accessory pathways by magnetocardiographic imaging

The magnetocardiogram (MCG) is a newly developed method that helps localize a cardiac current source. To test the clinical accuracy of a 7-channel biomagnetic system in the localization of early ventricular depolarization sites, the MCGs of 14 patients with Wolff-Parkinson-White (WPW) syndrome were recorded in a radiofrequency-shielded room. The locations of early ventricular depolarization sites were classified by standard 12-lead electrocardiograms (ECGs) and body surface isopotential mapping. The accessory pathways of 3 patients with WPW syndrome were located in the right free wall and in 11 patients in the left free wall. The three-dimensional (3-D) dipole location was computed every 2 ms from the onset of the QRS complex by the least-square method. These 3-D dipole locations were projected onto a gated magnetic resonance image in order to visualize the propagation of the calculated ventricular source. The results were compared with those obtained by body surface isopotential mapping, and electrocardiographic and electrophysiologic studies. The location of the deduced current dipole at 20 ms correlated well with the location of the accessory pathway by the body surface mappings in 12 of the 14 patients with WPW syndrome. The MCG is capable of precisely determining the 3-D location of a current source in a noninvasive manner and may be of potential benefit in the treatment of WPW syndrome by catheter ablation.


Atrial Natriuretic Factor and Isosorbide Dinitrate Modulate the Gating of ATP-Sensitive K+ Channels in Cultured Vascular Smooth Muscle Cells


Pathphysiologic significance of free and conjugated dopamines in congestive heart failure

sulfoconjugated dopamine constitutes the major portion of circulating or excreted dopamine, but its physiologic significance is still unknown. To test whether conjugated dopamine serves as a source of free dopamine in response to acute stress, plasma concentrations of free and conjugated dopamine were measured during an acute exacerbation of heart failure. The plasma concentration of conjugated dopamine decreased significantly during the acute phase of heart failure, whereas that of free dopamine increased. The plasma concentration of free dopamine decreased, whereas the concentration of conjugated dopamine increased as heart failure improved. An infusion of dopamine increased the plasma concentration of conjugated dopamine, suggesting that at least part of the excess active dopamine was detoxified through conjugation. The results of these tests with both conjugated and free dopamine are interconvertible and indicate that conjugated dopamine can serve as a reservoir of active dopamine.


Effects of vesnarinone (OPC-8212) on Ca(2+)-activated K channels and cytosolic Ca2+ in cultured smooth muscle cells from porcine coronary artery.

Vesnarinone is a new, non vasodilating cardiotonic agent. This study compared the effects of vesnarinone and amrinone, a phosphodiesterase (PDE) inhibitors with vasodilating actions, on cultured smooth muscle cells from the porcine coronary artery. Application of vesnarinone (10(-4) M) or amrinone (10(-4) M) to the bath solution in cell-attached patches activated the KCa channel having a conductance of 133 pS (bath 2.7 mM K, pipette 140 mM K). Application of vesnarinone to the cytosolic side had no direct effect on KCa channel activities in inside-out patches. Activation of the KCa channel was suppressed when the intracellular production of cAMP was suppressed by preincubation with carbachol (10(-6) M). Amrinone, but not vesnarinone, lowered [Ca2+]i in the K(+)-depolarized smooth muscle cells (K+ = 70 mM). These results suggest that vesnarinone exerts an additional effect on [Ca2+]i that is independent of PDE inhibition. The difference in the effects on [Ca2+]i in vascular smooth muscle cells may explain in part the differing actions of these agents on vascular relaxation.


Effects of Vesnarinone(OPC-8212)on Ca2+-Activated K Channels and Cytosolic Ca2+- in Cultured Smooth Muscle Cells from Porcine Coronary Artery


Hemopneumothorax secondary to multiple cavitary metastasis in angiosarcoma of the scalp

We report a case of hemopneumothorax secondary to multiple cavitary metastasis in the angiosarcoma of the scalp in an 86-year-old woman, who died of respiratory failure. At autopsy, multiple cavities were found in both lungs. Histologic specimen of the cavitary metastasis of the lung showed that tumor cells proliferated forming several tubular spaces and these tubular spaces seemed to communicate with the central cyst. These findings suggested that imperfect vessel-like structures of the cavitary metastasis are likely to break down and finally grow up to large thin-walled cavities.


僧帽弁逸脱における血中遊離型および硫酸抱合型カテコラミンの変動

僧帽弁逸脱における血中遊離型および硫酸抱合型カテコラミンの変動


心筋梗塞症の梗塞ベクトルと傷害ベクトルの発生機序

心筋梗塞症の梗塞ベクトルと傷害ベクトルの発生機序


心磁図法によるPベクトルの位置推定

心磁図法によるPベクトルの位置推定


肝硬変患者における自律神経機能:体表面平均加算化心電図法を用いた検討

肝硬変患者における自律神経機能:体表面平均加算化心電図法を用いた検討


心磁図法による心房性再分極波(Ta波)の検討

心磁図法による心房性再分極波(Ta波)の検討


心筋梗塞症の初期QRSベクトルと心室再分極ベクトル-心磁図法による電流源の位置

心筋梗塞症の初期QRSベクトルと心室再分極ベクトル-心磁図法による電流源の位置


Time- and frequency-domain analyses of signal averaged electrocardiograms in patients with diabetes mellitus

We recorded the signal-averaged electrocardiography (SAECG) of patients with diabetic retinopathy in order to clarify whether a ventricular conduction disturbance can be detected by time- or frequency-domain analysis of the SAECG. Twenty-four normal subjects (N group) and 20 patients with diabetic retinopathy [diabetes mellitus (DM) group] were studied. On time-domain analysis, the duration of the filtered QRS (f-QRS), the duration of the terminal QRS below 40 microV (LAS40) and the root-mean-square amplitude of the terminal 40 msec (RMS40) were measured. The frequency-domain analysis was performed using two windows. In each window, the ratio of the area under the spectral curve from 40 to 100 Hz was compared with that from 0 to 40 Hz and the area from 20 to 50 Hz was compared with that from 0 to 20 Hz. The LAS40 of the DM group was significantly prolonged when compared with the N group. The area ratio from 40 to 100 Hz versus 0 to 40 Hz significantly increased in the DM group when compared with the N group. These results suggest that SAECG can be used to detect abnormal electrical signals due to diabetic microangiopathy. Moreover, high frequency components of 40 to 100 Hz at the terminus of the QRS wave were most sensitive for abnormalities due to diabetic microangiopathy.


Circadian profile of heart rate variability in mitral valve prolapse syndrome


Time- and frequency-domain heart rate variabilities in patients with liver cirrhosis


Relationship between the ischemic myocardium and focus of ventricular tachycardia in old myocardial infarction


心房興奮伝播のMRI画像上の表示‐心磁図法による電流dipoleの位置推定‐

心房興奮伝播のMRI画像上の表示‐心磁図法による電流dipoleの位置推定‐


Prediction of the site of origin of ventricular premature beat by magnetocardiogram

心臓磁界測定による心室性期外収縮の心室最早期興奮部位の推定

心磁図による診断法を確立するために，生体内の電流源を三次元的に推定する心磁図法と，心電図同期MRI断層法を併用して，心室性期外収縮発生源の位置を推定した．推定された値は，体表面電位図法から推定される発生源とほぼ一致し，診断学的にも有用であることがわかった．


健常者の右側胸部誘導心電図所見に関する検討

健常者の右側胸部誘導心電図所見に関する検討


心磁図の臨床応用‐心室性不整脈の発生源の推定‐

心磁図の臨床応用‐心室性不整脈の発生源の推定‐


心磁図法によるQRS初期ベクトルの位置推定‐MRI画像上への表示

心磁図法によるQRS初期ベクトルの位置推定‐MRI画像上への表示


SQUIDを用いた心房興奮伝播のMRI画像上の表示

SQUIDを用いた心房興奮伝播のMRI画像上の表示

The Journal of Japan Biomagnetism and Bioelectromagnetics Society


心室性不整脈の発生源の推定-心電図と心磁図の比較

心室性不整脈の発生源の推定-心電図と心磁図の比較


マラソン前後における血中遊離型および硫酸抱合型カテコラミンの変動

マラソン前後における血中遊離型および硫酸抱合型カテコラミンの変動


7チャンネルSQUID磁束計による心臓磁界計測およびdipoleの位置推定

7チャンネルSQUID磁束計による心臓磁界計測およびdipoleの位置推定


Single moving dipole obtained from magnetic field of the heart in patients with left ventricular hypertrophy

Magnetocardiograms (MCGs) were recorded by means of a second-derivative SQUID (superconducting quantum interference device) magnetometer in 20 normal subjects and 28 patients with left ventricular overload to analyze the activation sequence of the heart and amplitude of estimated current source. In the normal subjects, the dipole was directed to the left and gradually superiorly 40 ms after the beginning of the QRS wave mainly due to the activation of the left ventricle. In the patients with hypertension, the direction and location of the dipoles were similar to those of the normal subjects, but their dipole moments were increased. In the patients with mitral regurgitation, the dipoles of late QRS were directed more inferiorly than in the normal subjects and their amplitude was increased. In the patients with aortic valve disease, the amplitude of the dipoles was increased markedly and their location was deviated more to the left than the dipoles of the normal subjects. We established the criterion for diagnosis of LVO from the dipole moment of 50 ms of 3.13 x 10(-3) A or more. The sensitivity of this criterion is significantly higher in the diagnosis of left ventricular overload than the electrocardiogram (ECG). The present study shows that the moving dipole method is useful to determine the increased electromotive force in patients with left ventricular overload and that sensitivity in diagnosis of left ventricular overload is increased.

Single moving dipole法により，高血圧，僧帽弁閉鎖不全，大動脈弁狭窄の症例について，推定dipoleの値を経時的定量的に求めた．健常例との比較により診断率の精度を比較検討し，各疾患の特徴と診断基準を明らかにした．


急性運動負荷前後での血中遊離型および硫酸抱合型カテコールアミンの変動

急性運動負荷前後での血中遊離型および硫酸抱合型カテコールアミンの変動

Japanese Journal of Clinical Pharmacology


左室負荷疾患における心磁図-Isomagnetic mapおよび single movingmoving dipole法による診断‐

心磁図による診断法を確立する目的で，磁界図の等価二重極を用いて推定dipoleを求めた．これを各時相で重ね合わせて，経時的に移動する moving dipoleとして表現した．健常群と左室負荷疾患群の moving dipoleを比較すると，電流源の大きさや経時変化および位置の情報を捉えやすく，疾患の特徴をよく反映していた．さらに電流源から体表面までの距離の影響を受けにくく，診断学的な有用性が認められた．


Endothelin blocks ATP-sensitive K+ channels and depolarizes smooth muscle cells of porcine coronary artery


正常例の初期QRS波のdipoleの位置推定‐心電図同期MRI画像上への表示‐

正常例の初期QRS波のdipoleの位置推定‐心電図同期MRI画像上への表示‐


心磁図法による心室最早期興奮部位の推定‐磁界分布図と体表面電位図·心表面マッピングとの対比‐


Changes in plasma free and sulfoconjugated catecholamines before and after acute physical exercise:Experimental and clinical studies.


Effects of vasopressin on K+ channels of vascular smooth muscle cells


Diagnosis of ventricular hypertrophy by single moving dipole

磁界図の等価二重極を用いて推定dipoleを求めた．これを各時相で重ね合わせて，経時的に移動する moving dipoleとして表現した．健常例と本態性高血圧症例，僧帽弁閉鎖不全症例大動脈弁凶作券閉鎖不全症例について moving dipoleを比較し，診断上の有用性を報告した

International Conference on Biomagnetism.


冠動脈平滑筋細胞におけるEndothelinの作用

冠動脈平滑筋細胞におけるEndothelinの作用


Vector U loop in patients with idiopathic cardiomyopathy

The U loops of vectorcardiograms were recorded in 50 normal subjects, 10 patients with dilated cardiomyopathy (DCM group), and 83 patients with hypertrophic cardiomyopathy (HCM group). The HCM group was divided into three subgroups: those with obstructive hypertrophic cardiomyopathy (HOCM), nonobstructive hypertrophic cardiomyopathy (HNCM), and apical hypertrophy (APH). The spatial characteristics of the U loop were examined qualitatively and quantitatively and were correlated with echocardiographic findings. The magnitude of the U loop was significantly larger in the HCM group, especially in the APH subgroup, than in the normal subjects, but it was not larger in the DCM group. The maximum U vector was significantly displaced anteriorly and to the right in the DCM and HCM groups, especially the APH and HNCM subgroups. In the HNCM and APH subgroups, the magnitude of the U loop correlated significantly with the thickness of the posterior wall of the left ventricle, but not with that of the interventricular septum. These findings suggest that the U loop is related to hypertrophy of the apex and the posterior wall of the left ventricle.


体表面電位図による健常小児のbreakthroughの検討

体表面電位図による健常小児のbreakthroughの検討

電位図において，心臓の興奮波が右室心外膜面に達した際にみられる breakthroughには，nicheと saddleの代表的なパターンがあるが，その成因は明らかにされていない．思春期において各パターンの認識率に性差，年齢差がみられることから，発育に伴う体型変化の関連を検討し，その成因を解明した．


健常小児の極大値，極小値よりみた体表面電位図の主要単極誘導心電図の検討

健常小児の極大値，極小値よりみた体表面電位図の主要単極誘導心電図の検討

体表面上の多数の誘導点より求めた心電位を等電位線で結ぶ電位図は，各瞬時の情報を示すものである．電位図に時間情報を加えて相補的に診断基準を高めるため，電位の各時相を重ね合わせた多誘導心電図を作成し，診断学的に有用な情報を含む主要単極心電図を抽出し，正常像の特徴を明らかにした．


Signal-averaging electrocardiogram in patients with diabetes mellitus


Isomagnetic maps in normal subjects. Comparison with isopotential maps

心筋の活動電流を捉えた磁界分布図と電位分布図の特質を明らかにするために，正常例の心室興奮伝播過程を比較した．心起電力を経時的，定量的に求めて比較し，その特徴を検討すると，磁界分布図では磁束計直下の胸壁面に平行な局所的電位変化を捉えやすく，12誘導心電図には反映されない左右上下方向 の心起電力変化が得られ，正常像および診断学上の有用な知見を得た．


Alteration of Strength-Interval Relation by Class I Antiarrhythmic Drugs in Normal and K-Depolarized Cardiac Muscle Fibers

Jpn J Appl Physiol(Japanese journal of applied physiology)


心臓磁界計測によるWPW症候群の副伝導路存在部位の推定

心臓磁界計測によるWPW症候群の副伝導路存在部位の推定


右脚ブロック所見を伴う右室拡張期負荷疾患における右室肥大の心磁図法による診断

右脚ブロック所見を伴う右室拡張期負荷疾患における右室肥大の心磁図法による診断


心磁図法によるWPW症候群の副伝導路存在部位の推定

心磁図法によるWPW症候群の副伝導路存在部位の推定


心磁図法によるWPW症候群の副伝導路存在部位の推定

心磁図法によるWPW症候群の副伝導路存在部位の推定

The Journal of Japan Biomagnetism and Bioelectromagnetics Society


Isomagnetic map of normal subjects - Comparison with isopotential map


U wave of high-speed and magnified electrocardiogram in left ventricular overloading

American Journal of Noninvasive Cardiology


Effects of lidocaine and quinidine on post-repolarization refractoriness after the basic and premature action potentials: consideration of aim of antiarrhythmic drug therapy

Antiarrhythmic drugs are often more effective in suppressing ventricular tachycardias than are background premature extrasystoles. The mechanism of action of these agents was examined by studies on the effects of lidocaine and quinidine on post-repolarization refractoriness of both basic and premature action potentials. In the absence of antiarrhythmic drugs, the excitability threshold was relatively constant after the end of repolarization of both basic and premature action potentials. In the presence of lidocaine or quinidine, the strength-interval curves were shifted to the right and superiorly, and the two drugs had different effects on the course of the strength-interval curve and Vmax recovery, presumably due to use-dependent V max block. Moreover, depressions of Vmax and excitability were more marked after the premature action potential than after the basic action potential. These results suggest that lidocaine and quinidine cause more depression of the excitability of second premature contractions than of first premature contractions, and also indicate that for protection against sustained ventricular tachycardias, it may not be necessary to suppress chronic premature ventricular contractions.


Vector U loop in patients with old myocardial infarction

The U loop of the vectorcardiogram was examined qualitatively and quantitatively in 100 normal subjects and 67 patients with old myocardial infarction, using a direct-writing vectorcardiograph with memory function. In the control group, the U loop was directed to the left, anteriorly and inferiorly, and it was inscribed counterclockwise in the horizontal plane. In patients with anterior myocardial infarction, the U loop tended to be displaced to the right, and in patients with inferior myocardial infarction to the right and superiorly. The shape of the U loop in patients was also different from that of normal subjects. The maximum U vector was significantly smaller in magnitude both in patients with anterior and inferior myocardial infarction than that of normal subjects (p less than 0.01). In patients with ventricular aneurysm, the magnitude of the maximum U vector was significantly smaller and its direction was displaced more to the right and posteriorly than those without aneurysm (p less than 0.01). In standard 12-lead electrocardiogram (ECG), observation of the U wave in patients with old myocardial infarction was difficult, especially in the limb lead, because of the small size of the U wave. Therefore, vectorcardiographic observation may be more useful than electrocardiographic observation for the analysis of the U wave in patients with old myocardial infarction.


Importance of Long-Term Follow-UpStudies on Health Check-Up : Relation between Electrocardiogram andHypertention

成人病検診における経年的観察の意義-血圧と心電図変化の関連について

血圧のレベルとその持続が心電図にどのような変化をもたらすかを検討し，830人の5∼10年間の検診記録を縦断的に追跡調査した．血圧上昇に伴い心電図は比較的早期から左房負荷，左室肥大が進展していた．予防医学的には，血圧をWHOの降圧目標のレベルよりも低くする必要があり，血圧を適正な値にコ ントロールすることは，心電図所見の改善にも有効であることを明らかにした．

Journal of health sciences, Faculty of Integrated Arts and Sciences, the University of Tokushima

徳島大学総合科学部健康科学紀要


Magnetocardiographic studies of ventricular repolarization in old inferior myocardial infarction

Isomagnetic maps of 50 normal subjects (control group) and 23 patients with old inferior myocardial infarction (IMI group) were recorded in order to analyse T wave abnormalities in inferior myocardial infarction. The T wave of the magnetocardiogram (MCG) in the control group showed negative deflections in the left upper portion and positive deflections in the right lower portion, thus resulting in a T vector directed leftward and inferiorly. The T wave of the IMI group was flat or positive in the left upper portion and flat or negative in the right lower portion, suggesting a T vector directed superiorly. In addition, opposing dipoles were observed in 36.4% of the IMI group; i.e. one directed superiorly, presumably due to inferior myocardial ischaemia, and the other directed inferiorly due to normal repolarization. Localized T vector abnormalities could be detected by the MCG in some cases, in which coronary T waves of the standard electrocardiogram had returned to normal. Furthermore, multiple dipoles were more frequently observed in the isomagnetic map than in the isopotential map (5 vs. 15; P less than 0.01). These results suggest that the MCG is helpful in diagnosing myocardial ischaemia when this is not detectable on the electrocardiogram.


右室収縮期負荷疾患の心磁図QRS波

右室収縮期負荷疾患の心磁図QRS波


糖尿病患者の心磁図T波に関する研究

糖尿病患者の心磁図T波に関する研究

The Japanese journal of clinical and experimental medicine


正常例における磁界分布図法による心起電力の解析‐体表面電位図との比較

正常例における磁界分布図法による心起電力の解析‐体表面電位図との比較


心磁図による異常T波の検討

心磁図による異常T波の検討


単離血管平滑筋細胞における膜電位固定‐血管攣縮との関連

単離血管平滑筋細胞における膜電位固定‐血管攣縮との関連


The T wave abnormality in the magnetocardiogram


QRS wave of the magnetocardiogram in right ventricular overloading: Correlation with right ventricular pressure


The isomagnetic maps of normal subjects and patients with right and left atrial overloading were recorded to determine the characteristic features of the magnetic field of atrial depolarization. The isomagnetic maps examined in this study indicated the instantaneous current source, which specifically localizes the current sources due to the right and left atria, respectively. The magnetic field recorded with a second derivative gradiometer clearly detected the cardiac current source from the right atrium, which is located close to the anterior chest wall, thus this method improved the diagnostic sensitivity for right atrial overloading. In patients with left atrial overloading, the isomagnetic map showed multiple dipoles due to the right and left atria, respectively, which are difficult to be detected by the electrocardiogram or isopotential map. These results suggest that the magnetocardiogram provides useful information on the current source to supplement information obtained by the conventional electrocardiogram.


The P wave of the magnetocardiogram (MCG) was investigated in normal subjects and in patients with right and left atrial overloading. In normal subjects, the MCG P wave was positive at right lower sternal sites and negative in the other portions. The current source deduced from the MCG and the isomagnetic map was directed inferiorly and to the left throughout the entire phase of atrial activation. In patients with right atrial overloading, the direction of the current source deduced from the MCG was similar to that of normal subjects, but its amplitude was significantly greater. In left atrial overloadings, a negative-positive biphasic P wave was seen more frequently than in normal subjects at left parasternal sites. In the late phase of atrial activation, the MCG could detect the two dipoles, i.e. one directed inferiorly and other directed to the left. These dipoles might correspond to right and left atrial activities, respectively. These results show that the MCG might add useful information on current source to the conventional electrocardiogram.


Isomagnetic maps in right ventricular overloading

Isomagnetic maps were recorded in normal subjects and in patients with systolic overloading of the right ventricle. The isomagnetic maps examined in this study indicated the instantaneous current source of the heart by applying the "corkscrew rule." The magnetic field recorded by a second derivative gradiometer detected clearly the cardiac current source from the right ventricle, which is located close to the anterior chest wall, and improved diagnostic sensitivity. Moreover, the isomagnetic map showed multiple dipoles, which are difficult to detect in the electrocardiogram or isopotential map. These results suggest that the magnetocardiogram provides useful information on current sources to supplement information obtained by the conventional electrocardiogram.


Analysis of the T wave of the magnetocardiogram in patients with essential hypertension by means of isomagnetic and vector arrow maps


心磁図法による右室負荷の診断

心磁図法による右室負荷の診断


右室負荷時の心磁図QRS波心磁図法による右室負荷の診断

右室負荷時の心磁図QRS波心磁図法による右室負荷の診断


心磁図法による心筋梗塞症のT波の解析

心磁図法による心筋梗塞症のT波の解析


心磁界計測による副伝導路の推定

心磁界計測による副伝導路の推定


心磁図法による陳旧性下壁梗塞症の心室再分極ベクトルの検討

心磁図法による陳旧性下壁梗塞症の心室再分極ベクトルの検討


心磁図法による左室収縮期負荷疾患における再分極異常の検討

心磁図法による左室収縮期負荷疾患における再分極異常の検討


側面心磁図QRS波に関する研究‐健常群および心筋梗塞群との対比

側面心磁図QRS波に関する研究‐健常群および心筋梗塞群との対比


心磁図法の臨床応用-心筋障害の診断における心磁図法の有用性の検討

心磁図法の臨床応用-心筋障害の診断における心磁図法の有用性の検討


心磁図法の臨床的有用性の検討

心磁図法の臨床的有用性の検討

第3回 生体·生理工学シンポジウム論文集

第3回 生体·生理工学シンポジウム論文集


Vector U loop in patients with left ventricular overloading


Vector U loop in patients with right ventricular overloading

The U loop of the vectorcardiogram (VCG) was examined qualitatively and quantitatively in 126 normal subjects, 15 subjects with complete right bundle branch block (CRBBB group) and 58 patients with right ventricular overloading (RVO group), using a direct-writing vectorcardiograph with memory function. In normal subjects the U loop was directed similarly to the T loop, i.e., to the left, anteriorly and inferiorly. In the CRBBB group, maximum U vector was smaller, but its direction was not significantly different from that in normal subjects. In the RVO group, the U loop tended to be displaced posteriorly and to the left and was significantly greater in magnitude than that in normal subjects in the horizontal (P less than 0.01) and frontal (P less than 0.001) planes. In the RVO group, a good correlation was found between the direction of maximum U vector and right ventricular systolic pressure. In some cases of the RVO group, the U loop was the only abnormality suggesting right ventricular overloading. These findings suggest that abnormality of the U loop is a good indicator in a diagnosis of right ventricular overloading.


右室負荷時の心磁図QRS波に関する検討-特徴的波形の定量的検討と出現部位

右室負荷時の心磁図QRS波に関する検討-特徴的波形の定量的検討と出現部位


左室収縮期負荷疾患T波の磁界分布図‐体表面電位図との対比

左室収縮期負荷疾患T波の磁界分布図‐体表面電位図との対比


心磁界計測による心室再分極の検討

心磁界計測による心室再分極の検討

Japanese Journal of Medical Electronics and Biological Engineering


Magnetocardiographic P waves in normal subjects and patients with mitral stenosis

The P wave of the magnetocardiogram (MCG) was investigated in normal subjects and patients with mitral stenosis to determine its characteristics in normal conditions and left atrial overloading (LAO) and to analyze atrial activation by a magnetic field. In normal subjects, the MCG P wave was negative in left parasternal sites and positive in right lower sternal sites. The current source deduced from the MCG pattern and isomagnetic map was directed inferiorly and to the left through the entire phase of atrial activation, suggesting that in most normal cases the P wave reflects right atrial activity. In patients with mitral stenosis, a negative-positive biphasic P wave was seen more frequently than in normal subjects in left parasternal sites (p less than 0.005). In the late phase of atrial activation, the current source deduced from the isomagnetic map was shifted superiorly and to the left, suggesting an increased leftward force due to LAO. The MCG was similar in sensitivity to the ECG, for diagnosis of LAO, but in a few cases LAO could be detected from the MCG but not the ECG. These findings suggest that the MCG is clinically useful for diagnosis of LAO.


健常小児(10∼15歳)の体表面電位図-電位と心室興奮時間の正常値について

健常小児(10∼15歳)の体表面電位図-電位と心室興奮時間の正常値について

小児の体表面電位図の正常像とそれにおよぼす生理的諸因子の影響を明らかにする目的で，10∼15歳の小児 216例を検討した．心臓の興奮伝播過程に伴う電位図および電位と心室興奮時間は個人差が大きく，性差，年齢差とともに体型や運動の影響がみられ，発育発達との関連が深い．臨床応用にはこれら諸要 因を考慮する必要があることを指摘した．


狭心症に対するニトログリセリン軟膏の使用経験

狭心症に対するニトログリセリン軟膏の使用経験


FFI Journal(Foods and Food Ingredients Journal of Japan)


Tripsin-like activities and human airway trypsin-like protease (HAT) levels in airway secretions from healthy subjects and patients with chronic airway diseases.


Biomagnetic measurement of gastric mechanical motility using a high-temperature SQUID imaging.


Source localization of initial QRS vector in patients with idiopathic cardiomyopathy : Comparison with normal subjects and patients with anterior myocardial infarction.


長時間運動後のエネルギー代謝におよぼす影響

長時間運動後のエネルギー代謝におよぼす影響


Influence of exercise and food intake on post-exercise carbohydrate and fat metabolism

Proceedings FISU/CESU Conference The 18th Universiade 1995 Fukuoka