Earthquake Preparedness for Operating Room Staff: Lessons Learned From Experiences and the Literature

Earthquakes pose hazards to health care workers and patients in operating rooms. Proactive planning based on insights gained from past experiences is crucial for enhancing safety. Through a comprehensive literature review, we summarize challenges and lessons learned from real earthquake events to inform the development of effective safety measures in operating rooms. Additionally, we discuss the anesthesiologist's role in crisis management.


全身麻酔手術中にラテックスアレルギーによるアナフィラキシーショックをきたした一例

Japanese Journal of Clinical Ophthalmology


Efficacy and Safety of Sugammadex (Org 25969) in Reversing Deep Neuromuscular Block Induced by Rocuronium or Vecuronium in Japanese Patients

スガマデクスナトリウム(MK-8616, Org25969)の筋弛緩拮抗作用ー深い筋 弛緩状態からの回復ー

Efficacy and safety of sugammadex in reversing neuromuscular block induced by rocuronium or vecuronium were investgated in Japanese patients. We studied 99 Japanese patients undergoing surgery requiring general anesthesia. Patients were allocated randomly to receive intubation dose of rocuronium or vecuronium. During surgery, patients received additional dose of rocuronium or vecuronium for maintenance of deep block. At 1-2 PTC, 0.5-8.0 mg . kg-1 of sugammadex was administered. The neuromuscular block was monitored with acceleromyography using TOF stimuli. Sevoflurane was administered to all treatment groups after intubation. For the rocuronium-induced neuromuscular block, the mean recovery time of the T4/T1 ratio to 0.9 decreased from 66.9 min in the sugammadex 0.5 mg kg-1 group to 1.3 min in the sugammadex 8.0 mg kg-1 group. For the vecuronium-induced neuromuscular block it decreased from 79.5 min in the sugammadex 0.5 mg . kg-1 group to 2.9 min in the sugammadex 8.0 mg . kg-1 group. No clinical evidence of recurarization or residual curarization was observed. The efficacy and safety of sugammadex were confirmed in Japanese surgical patients for reversal from deep block.


Trends in electrocardiographic R-wave amplitude during intraoperative pneumothorax

Tension pneumothorax is a rare but potentially life-threating complication of laparoscopic fundoplication. Electrocardiogram (ECG) changes may be used in the diagnosis of intraoperative tension pneumothorax. This case study examines a pediatric patient who underwent laparoscopic fundoplication. Sudden decreases in oxygen saturation were observed during dissection, although the patient's decrease in blood pressure was less marked. Manual ventilation with high inspiratory pressure and inspiratory pause improved oxygenation. The amplitude of the R-wave decreased from 0.8 mV to 0.3 mV in 5 seconds. Twenty minutes later, oxygen saturation decreased again, the R-wave amplitude decreased from 0.3 mV to 0.1 mV in 1 second, and the decrease in blood pressure was marked. Manual ventilation with high inspiratory pressure improved oxygenation, blood pressure, and R-wave amplitude within two minutes. After conversion to open surgery, the cardiorespiratory condition gradually improved, but the R-wave amplitude did not fully recover, even at the end of surgery. Right-side pneumothorax was subsequently confirmed by postoperative chest X-ray. Chest drains were inserted after surgery. This case suggests that trends in R-wave amplitude are potential indicators of intraoperative tension pneumothorax.

The Journal of Medical Investigation : JMI


術中冠攣縮が疑われた糖尿病患者の1症例

術中冠攣縮が疑われた糖尿病患者の1症例


Cardioprotective effects of hyperkalemia during smulated ischemia/reperfusion in neonatal rat cardiomyocytes - Preservation of Na+/K+-ATPase activity -

Hyperkalemia has multimodal effects on myocardial protection during ischemia/reperfusion. The preservation of Na(+)/K(+)-ATPase activity induced by hyperkalemia may have critical impact on myocardial protection. To elucidate the roles of hyperkalemia (16 mM) and Na(+)/K(+)-ATPase inhibition (100 µM ouabain) in myocardial protection during simulated ischemia (5 mM NaCN and 5.5 mM 2-deoxyglucose)/reperfusion, we measured loss of membrane integrity and bleb formation using a vital dye calcein AM in cultured neonatal rat cardiomyocytes. The control perfusate was switched to treatment solution for 15 min, followed by reperfusion for 30 min. In a second set of experiments, myocardial excitability and diastolic intracellular calcium ion concentration ([Ca(2+)]i) were measured during a 45-min treatment using a calcium-sensitive fluorescent dye fluo-4 AM. Simulated ischemia/reperfusion under ouabain treatment induced loss of membrane integrity, which was suppressed by hyperkalemia. Simulated ischemia/reperfusion induced bleb formation, which was accelerated by ouabain. Hyperkalemia delayed and inhibited the increase in diastolic [Ca(2+)]i induced by simulated ischemia. Furthermore, hyperkalemia almost completely inhibited the effects of ouabain on the diastolic [Ca(2+)]i during ischemia. These results suggest that hyperkalemia during ischemia is cardioprotective against ischemia/reperfusion insults and that hyperkalemia inhibits the effects of ouabain during ischemia.


Anesthesia for deep brain stimulation in a patient with X-linked dystonia-parkinsonism/Lubag disease.

Lubag disease is a genetic X-linked dystonia-parkinsonism syndrome afflicting Filipino men. This disease is characterized by dystonia dominating the first 10-15 years of the disorder, which is associated with or replaced by parkinsonian features in later years of life. A 49-year-old man with Lubag disease underwent general anesthesia for deep brain stimulation (DBS) surgery. Anesthesia was maintained mainly with propofol, remifentanil, rocuronium bromide, and sevoflurane. During magnetic resonance imaging, the patient was anesthetized with midazolam, fentanyl, and rocuronium bromide. The surgery was completed safely using these anesthetic agents. After DBS, some symptoms including involuntary movement improved within 10 days.


Two Cases of Anaphylactoid Reaction after Administration of Sugammadex

スガマデクス投与後にアナフィラキシー様反応を呈した2症例

Anaphylaxis during anesthesia is a rare but life-threatening event. Sugammadex is a recently introduced drug that was specifically designed for the reversal of rocuroium and vecuronium-induced neuromuscular block. We describe the cases of a 74-year-old man and a 29-year-old man who developed an anaphylactoid reaction to sugammadex, presenting with cardiovascular collapse. Initial management consisted of fluid administration and intermittent i.v. ephedrine, epinephrine, and hydrocortisone. The patients made uncomplicated recovery and were discharged.


Anesthetic Management with Muscle Relaxant in a Patient with Amyotrophic Lateral Sclerosis

筋萎縮性側索硬化症患者の麻酔経験

A 31-year-old woman with amyotrophic lateral sclerosis (ALS) with respiratory muscle paralysis was scheduled for tracheotomy. After applying standard neuromuscular monitoring devices, general anesthesia was induced and maintained with propofol, remifentanil, rocuronium, and sevoflurane. Sugammadex is a potent agent for reversal of neuromuscular blockade by rocuronium. The patient emerged from general anesthesia smoothly using sugammadex; however, assisted respiration was continued for possible prolongation of the effect of muscle relaxant. The postoperative course was uneventful, and she was discharged without any discomfort.


Anesthesia for a patient with severe tracheal stenosis due to thoracic aortic aneurysm

胸部大動脈瘤により高度気管狭窄を呈した症例の麻酔経験

Tracheobronchial compression is a well-recognized complication of thoracic aortic aneurysm. We describe the anesthetic management of a patient with severe tracheal stenosis due to thoracic aortic aneurysm. An 81-year-old woman was scheduled for endovascular aortic stent graft placement. Computed tomographic (CT) scans showed that the narrowest diameter of the trachea was 3 x 18 mm. Awake fiberoptic intubation was selected for anesthesia induction, and percutaneous cardiopulmonary support (PCPS) was ready to be established prior to induction of anesthesia. We successfully inserted ID 6.0 mm spiral tube beyond the tracheal compression using bronchoscope and induced hypotension. The operation was completed successfully without any adverse events. We conclude that, in patients with thoracic aortic aneurysm, careful attention should be paid not only to circulation but to respiration.


The use of sugammadex in two patients with myasthenia gravis

重症筋無力症患者にロクロニウムとスガマデクスを使用した2症例

The Journal of Japan Society for Clinical Anesthesia


General anesthesia for electroconvulsive therapy with Brugada electrocardiograph pattern.

Brugada syndrome is characterized by an electrocardiograph pattern of right bundle-branch block and has an increased risk for cardiac arrest due to malignant arrhythmia. We describe the successful anesthetic management for electroconvulsive therapy in a patient with Brugada electrocardiograph pattern. Patients with Brugada ECG pattern are not recommended to use neostigmine which augments ST elevation. Sugammadex was administered as a neuromuscular reversal agent in this case. Sugammadex provides rapid reversal of profound rocuronium-induced neuromuscular blockade under propofol anesthesia.


Anesthetic management of a patient with Becker muscular dystrophy

ベッカー型筋ジストロフィ症患者の麻酔経験

We experienced anesthetic management of a patient with Becker muscular dystrophy. He had advanced dilated cardiomyopathy and high serum CK in the preoperative examinations. Anesthesia was planned to avoid triggering malignant hyperthermia or rhabdomyolysis and hemodynamic changes. Propofol, remifentanil and a minimum dose of rocuronium bromide were used for anesthetic induction and maintainance. Arterial pressure, cardiac output and stroke volume variation were monitored by Flotrac sensor. There were no adverse events observed during the anesthetic management. In conclusion, total intravenous anesthesia with the administration of rocuronium and circulatory monitoring by Flotrac sensor could be safe and efficient for anesthetic management of patients with Becker muscular dystrophy.


[Anesthetic management of a child with Angelman's syndrome].

Angelman症候群の麻酔経験

Angelman syndrome is a hereditary disease described by Angelman. The clinical features of Angelman syndrome are characterized by mental retardation, puppet-like ataxia, easily excitable personality, seizures, paroxysmal laughter, strabismus and macroglossia. A 4-year-old girl with Angelman syndrome underwent strabismus repair under general anesthesia. Anesthesia was slowly induced with sevoflurane in oxygen and maintained with air, oxygen, propofol and remifentanil. Tracheal intubation was performed after administration of rocuronium. During and after anesthesia, no adverse events regarding circulatory and respiratory systems occurred. However, this case demonstrates that it is necessary to pay attention to airway troubles including the difficulty of tracheal intubation, management of body temperature and chronotropic action or respiratory depression by anesthetic agents.


Involvement of adenosine triphosphate-sensitive potassium channels in the response of membrane potential to hyperosmolality in cultured human aorta endothelial cells.

The membrane potential of endothelial cells is an important determinant of endothelial functions, including regulation of vascular tone. We investigated whether adenosine triphosphate-sensitive potassium (K(ATP)) channels were involved in the response of membrane potential to hyperosmolality in cultured human aorta endothelial cells. The voltage-sensitive fluorescent dye, bis-(1,3-diethylthiobarbiturate)trimethine oxonol, was used to assess relative changes in membrane potential semiquantitatively. To investigate the effect of mannitol-, sucrose-, and NaCl-induced hyperosmolality on membrane potential, cells were continuously perfused with Earle's balanced salt solution (285 mOsm/kg H(2)O) containing 200 nM bis-(1,3-diethylthiobarbiturate)trimethine oxonol and exposed to 315 and 345 mOsm/kg H(2)O hyperosmotic medium sequentially in the presence and absence of 1 muM glibenclamide, a well-known K(ATP) channel blocker. Hyperosmotic mannitol significantly induced hyperpolarization of the endothelial cells, which was prevented by 1 microM glibenclamide (n = 6). Estimated changes of membrane potential at 315 and 345 mOsm/kg H(2)O were 13 +/- 8 and 21 +/- 8 mV, respectively. Hypertonic sucrose induced similar changes. However, although hypertonic saline also significantly induced hyperpolarization of the endothelial cells (n = 6), the hyperpolarization was not prevented by 1 muM glibenclamide. In conclusion, K(ATP) channels may participate in hyperosmotic mannitol- and sucrose-induced hyperpolarization, but not in hypertonic saline-induced hyperpolarization in cultured human aorta endothelial cells.


Molecular mechanisms underlying ketamine-mediated inhibition of sarcolemmal adenosine triphosphate-sensitive potassium channels.

Ketamine inhibits adenosine triphosphate-sensitive potassium (KATP) channels, which results in the blocking of ischemic preconditioning in the heart and inhibition of vasorelaxation induced by KATP channel openers. In the current study, the authors investigated the molecular mechanisms of ketamine's actions on sarcolemmal KATP channels that are reassociated by expressed subunits, inwardly rectifying potassium channels (Kir6.1 or Kir6.2) and sulfonylurea receptors (SUR1, SUR2A, or SUR2B). The authors used inside-out patch clamp configurations to investigate the effects of ketamine on the activities of reassociated Kir6.0/SUR channels containing wild-type, mutant, or chimeric SURs expressed in COS-7 cells. Ketamine racemate inhibited the activities of the reassociated KATP channels in a SUR subtype-dependent manner: SUR2A/Kir6.2 (IC50 = 83 microM), SUR2B/Kir6.1 (IC50 = 77 microM), SUR2B/Kir6.2 (IC50 = 89 microM), and SUR1/Kir6.2 (IC50 = 1487 microM). S-(+)-ketamine was significantly less potent than ketamine racemate in blocking all types of reassociated KATP channels. The ketamine racemate and S-(+)-ketamine both inhibited channel currents of the truncated isoform of Kir6.2 (Kir6.2DeltaC36) with very low affinity. Application of 100 mum magnesium adenosine diphosphate significantly enhanced the inhibitory potency of ketamine racemate. The last transmembrane domain of SUR2 was essential for the full inhibitory effect of ketamine racemate. These results suggest that ketamine-induced inhibition of sarcolemmal KATP channels is mediated by the SUR subunit. These inhibitory effects of ketamine exhibit specificity for cardiovascular KATP channels, at least some degree of stereoselectivity, and interaction with intracellular magnesium adenosine diphosphate.


Molecular Mechanisms of the Inhibitory Effects of Bupivacaine, Levobupivacaine, and Ropivacaine on Sarcolemmal Adenosine Triphosphate-sensitive Potassium Channels in the Cardiovascular System.

Sarcolemmal adenosine triphosphate-sensitive potassium (KATP) channels in the cardiovascular system may be involved in bupivacaine-induced cardiovascular toxicity. The authors investigated the effects of local anesthetics on the activity of reconstituted KATP channels encoded by inwardly rectifying potassium channel (Kir6.0) and sulfonylurea receptor (SUR) subunits. The authors used an inside-out patch clamp configuration to investigate the effects of bupivacaine, levobupivacaine, and ropivacaine on the activity of reconstituted KATP channels expressed in COS-7 cells and containing wild-type, mutant, or chimeric SURs. Bupivacaine inhibited the activities of cardiac KATP channels (IC50 = 52 microm) stereoselectively (levobupivacaine, IC50 = 168 microm; ropivacaine, IC50 = 249 microm). Local anesthetics also inhibited the activities of channels formed by the truncated isoform of Kir6.2 (Kir6.2 delta C36) stereoselectively. Mutations in the cytosolic end of the second transmembrane domain of Kir6.2 markedly decreased both the local anesthetics' affinity and stereoselectivity. The local anesthetics blocked cardiac KATP channels with approximately eightfold higher potency than vascular KATP channels; the potency depended on the SUR subtype. The 42 amino acid residues at the C-terminal tail of SUR2A, but not SUR1 or SUR2B, enhanced the inhibitory effect of bupivacaine on the Kir6.0 subunit. Inhibitory effects of local anesthetics on KATP channels in the cardiovascular system are (1) stereoselective: bupivacaine was more potent than levobupivacaine and ropivacaine; and (2) tissue specific: local anesthetics blocked cardiac KATP channels more potently than vascular KATP channels, via the intracellular pore mouth of the Kir6.0 subunit and the 42 amino acids at the C-terminal tail of the SUR2A subunit, respectively.


Effect of propofol on hypotonic swelling-induced membrane depolarization in human coronary artery smooth muscle cells.

Stretch (mechanical stress)-induced membrane depolarization of smooth muscle may contribute to basal vascular tone and myogenic control. Propofol induces vasodilation and inhibits myogenic control. Hypotonic swelling was used as a model of mechanical stress. The authors investigated the effects of propofol and 5-nitro-2-(3-phenylpropylamino)benzoic acid, a chloride channel and nonselective cation channel blocker, on hypotonicity-induced membrane depolarization in cultured human coronary artery smooth muscle cells. A voltage-sensitive fluorescent dye, bis-(1,3-diethylthiobarbiturate)trimethine oxonol, was used to assess relative changes in membrane potential semiquantitatively. The cells were continuously perfused with Earle's balanced salt solution containing 200 nM bis-(1,3-diethylthiobarbiturate)trimethine oxonol and exposed sequentially to isotonic and hypotonic medium. In a second series of experiments, the cells were exposed to hypotonic media in the presence and absence of 5-nitro-2-(3-phenylpropylamino)benzoic acid or propofol. The relative fluorescence values at 10, 20, and 30% hypotonicity were 147 +/- 29, 214 +/- 74, and 335 +/- 102% of baseline, respectively. The changes were all significantly different from the isotonic time control group. In the presence of 200 microM 5-nitro-2-(3-phenylpropylamino)benzoic acid or 0.1, 1, 10, or 100 microg/ml propofol, the relative fluorescence values at 30% hypotonicity were 87 +/- 17, 194 +/- 27, 160 +/- 18, 130 +/- 18, and 84 +/- 15%, respectively. These changes were significantly less than the 30% for the hypotonic control (246 +/- 23%). These results suggest that volume-sensitive chloride channels and nonselective cation channels may participate in hypotonicity-induced membrane depolarization and that propofol inhibits hypotonicity-induced membrane depolarization in coronary artery smooth muscle.


Molecular mechanisms of the inhibitory effects of propofol and thiamylal on sarcolemmal adenosine triphosphate-sensitive potassium channels.

Both propofol and thiamylal inhibit adenosine triphosphate-sensitive potassium (KATP) channels. In the current study, the authors investigated the effects of these anesthetics on the activity of recombinant sarcolemmal KATP channels encoded by inwardly rectifying potassium channel (Kir6.1 or Kir6.2) genes and sulfonylurea receptor (SUR1, SUR2A, or SUR2B) genes. The authors used inside-out patch clamp configurations to investigate the effects of propofol and thiamylal on the activity of recombinant KATP channels using COS-7 cells transfected with various types of KATP channel subunits. Propofol inhibited the activities of the SUR1/Kir6.2 (EC50 = 77 microm), SUR2A/Kir6.2 (EC50 = 72 microm), and SUR2B/Kir6.2 (EC50 = 71 microm) channels but had no significant effects on the SUR2B/Kir6.1 channels. Propofol inhibited the truncated isoform of Kir6.2 (Kir6.2DeltaC36) channels (EC50 = 78 microm) that can form functional KATP channels in the absence of SUR molecules. Furthermore, the authors identified two distinct mutations R31E (arginine residue at position 31 to glutamic acid) and K185Q (lysine residue at position 185 to glutamine) of the Kir6.2DeltaC36 channel that significantly reduce the inhibition of propofol. In contrast, thiamylal inhibited the SUR1/Kir6.2 (EC50 = 541 microm), SUR2A/Kir6.2 (EC50 = 248 microm), SUR2B/Kir6.2 (EC50 = 183 microm), SUR2B/Kir6.1 (EC50 = 170 microm), and Kir6.2DeltaC36 channels (EC50 = 719 microm). None of the mutants significantly affects the sensitivity of thiamylal. These results suggest that the major effects of both propofol and thiamylal on KATP channel activity are mediated via the Kir6.2 subunit. Site-directed mutagenesis study suggests that propofol and thiamylal may influence Kir6.2 activity by different molecular mechanisms; in thiamylal, the SUR subunit seems to modulate anesthetic sensitivity.


Phenylephrine increases pulmonary blood flow in children with tetralogy of Fallot.

Although it has been reported that the increase in blood pressure improves arterial oxygen saturation (SaO(2)) in children with tetralogy of Fallot, no prospective study has demonstrated that an increase in blood pressure induces an increase in pulmonary blood flow in these patients. The purpose of this study was to see whether a phenylephrine-induced increase in systemic blood pressure increased pulmonary blood flow, resulting in improved arterial oxygenation in tetralogy of Fallot. In 14 consecutive children with tetralogy of Fallot (2-32 months old), transesophageal pulsed Doppler signals of left upper pulmonary venous flow (PVF) velocity were recorded before and four minutes after 10 micro g x kg(-1) of phenylephrine i.v. Simultaneously, arterial blood gas analysis and hemodynamic measurements were performed. The minute distance (MD) was calculated as the product of the heart rate and the sum of time-velocity integrals of PVF. Phenylephrine iv increased mean arterial blood pressure from 54 +/- 8 mmHg to 73 +/- 10 mmHg. This phenylephrine-induced hypertension significantly increased SaO(2) and MD (92.0 +/- 7.5 vs 95.0 +/- 5.0% and 1318 +/- 344 vs 1533 +/- 425 cm x min(-1), respectively). There was a significant correlation (r = 0.72) between the change in MD and the change in SaO(2). Our results suggest that the phenylephrine-induced increase in systemic blood pressure produces an increase in pulmonary blood flow in tetralogy of Fallot. Our results further suggest that this increase in pulmonary blood flow is involved in the mechanism of phenylephrine-induced improvement of arterial oxygenation in tetralogy of Fallot.


Propofol inhibits volume-sensitive chloride channels in human coronary artery smooth muscle cells.

Volume-sensitive chloride channels (VSCC) play an important role in regulation of cell volume and electrical activity. Activation of vascular smooth muscle VSCC causes smooth muscle depolarization and contraction. We investigated the effects of propofol on VSCC in cultured human coronary artery smooth muscle cells by using the chloride-sensitive dye 6-methoxy-N-ethylquinolinium (MEQ). To activate VSCC, cells were superfused for 2 min with hypotonic gluconate solutions and then potassium thiocyanate solution. The percentage reduction in MEQ fluorescence during 60 s in the presence of potassium thiocyanate was measured and used as an index of VSCC activity. 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB), a well characterized chloride channel blocker, and propofol were dissolved in hypotonic gluconate solution to test their effect on VSCC activity. The reduction in fluorescence was inversely related to osmolality, indicating that activation of VSCC is osmolality dependent. Hypotonic gluconate solution (210 mOsm/kg H(2)O) reduced fluorescence by 38.9% +/- 2.6% of the baseline value. The reduction in fluorescence was dose-dependently inhibited by NPPB. Propofol at 0.3, 1, 3, 10, 30, and 100 micro g/mL significantly inhibited the reduction in fluorescence to 23.6% +/- 4.8%, 19.7% +/- 7.4%, 18.2% +/- 3.5%, 17.6% +/- 5.0%, 15.8% +/- 3.1%, and 10.3% +/- 3.9% of the baseline value, respectively. Our results indicate that propofol inhibits VSCC in a dose-dependent manner in human coronary artery smooth muscle cells.


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).


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.


Plasma viscosity and cerebral blood flow

We hypothesized that the response of cerebral blood flow (CBF) to changing viscosity would be dependent on "baseline" CBF, with a greater influence of viscosity during high-flow conditions. Plasma viscosity was adjusted to 1.0 or 3.0 cP in rats by exchange transfusion with red blood cells diluted in lactated Ringer solution or with dextran. Cortical CBF was measured by H(2) clearance. Two groups of animals remained normoxic and normocarbic and served as controls. Other groups were made anemic, hypercapnic, or hypoxic to increase CBF. Under baseline conditions before intervention, CBF did not differ between groups and averaged 49.4 +/- 10.2 ml. 100 g(-1). min(-1) (+/-SD). In control animals, changing plasma viscosity to 1. 0 or 3.0 cP resulted in CBF of 55.9 +/- 8.6 and 42.5 +/- 12.7 ml. 100 g(-1). min(-1), respectively (not significant). During hemodilution, hypercapnia, and hypoxia with a plasma viscosity of 1. 0 cP, CBF varied from 98 to 115 ml. 100 g(-1). min(-1). When plasma viscosity was 3.0 cP during hemodilution, hypercapnia, and hypoxia, CBF ranged from 56 to 58 ml. 100 g(-1). min(-1) and was significantly reduced in each case (P < 0.05). These results support the hypothesis that viscosity has a greater role in regulation of CBF when CBF is increased. In addition, because CBF more closely followed changes in plasma viscosity (rather than whole blood viscosity), we believe that plasma viscosity may be the more important factor in controlling CBF.

American Journal of Physiology, Heart and Circulatory Physiology


Cerebral blood flow during hemodilution and hypoxia in rats: Role of ATP-sensitive potassium channels

Hypoxia and hemodilution both reduce arterial oxygen content (CaO(2)) and increase cerebral blood flow (CBF), but the mechanisms by which hemodilution increases CBF are largely unknown. ATP-sensitive potassium (K(ATP)) channels are activated by intravascular hypoxia, and contribute to hypoxia-mediated cerebrovasodilatation. Although CaO(2) can be reduced to equal levels by hypoxia or hemodilution, intravascular PO(2) is reduced only during hypoxia. We therefore tested the hypothesis that K(ATP) channels would be unlikely to contribute to cerebrovasodilatation during hemodilution. Glibenclamide (19.8 microg) or vehicle was injected into the cisterna magna of barbiturate-anesthetized rats. The dose of glibenclamide was chosen to yield an estimated CSF concentration of 10(-4) M. Thirty minutes later, some animals underwent either progressive isovolumic hemodilution or hypoxia (over 30 minutes) to achieve a CaO(2) of approximately 7.5 mL O(2)/dL. Other animals did not undergo hypoxia or hemodilution and served as controls. Six groups of animals were studied: control/vehicle (n=4), control/glibenclamide (n=4), hemodilution/vehicle (n=10), hemodilution/glibenclamide (n=10), hypoxia/vehicle (n=10), and hypoxia/glibenclamide (n=10). CBF was then measured with (3)H-nicotine in the forebrain, cerebellum, and brain stem. In control/vehicle rats, CBF ranged from 72 mL. 100 g(-1). min(-1) in forebrain to 88 mL. 100 g(-1) x min(-1) in the brain stem. Glibenclamide treatment of control animals did not influence CBF in any brain area. Hemodilution increased CBF in all brain areas, with flows ranging from 128 mL. 100 g(-1) x min(-1) in forebrain to 169 mL. 100 g(-1) x min(-1) in the brain stem. Glibenclamide treatment of hemodiluted animals did not affect CBF in any brain area. Hypoxia resulted in a greater CBF than did hemodilution, ranging from 172 mL. 100 g(-1) x min(-1) in forebrain to 259 mL. 100 g(-1) x min(-1) in the brain stem. Glibenclamide treatment of hypoxic animals significantly reduced CBF in all brain areas (P<0.05). Both hypoxia and hemodilution increased CBF. Glibenclamide treatment significantly attenuated the CBF increase during hypoxia but not after hemodilution. This finding supports our hypothesis that K(ATP) channels do not contribute to increasing CBF during hemodilution. Because intravascular PO(2) is normal during hemodilution, this finding supports the hypothesis that intravascular PO(2) is an important regulator of cerebral vascular tone and exerts its effect in part by activation of K(ATP) channels in the cerebral circulation.


Hemodilution, cerebral O2 delivery and cerebral blood flow: a study using hyperbaric oxygenation

Hemodilution reduces blood viscosity and O2 content (CaO2) and increases cerebral blood flow (CBF). Viscosity and CaO2 may contribute to increasing CBF after hemodilution. However, because hematocrit is the major contributor to blood viscosity and CaO2, it has been difficult to assess their relative importance. By varying blood viscosity without changing CaO2, prior investigation in hemodiluted animals has suggested that both factors play roughly equal roles. To further investigate the relationship of hemodilution, blood viscosity, CaO2, and CBF, we took the opposite approach in hemodiluted animals, i.e., we varied CaO2 without changing blood viscosity. Hyperbaric O2 was used to restore CaO2 to normal after hemodilution. Pentobarbital sodium-anesthetized rats underwent isovolumic hemodilution with 6% hetastarch, and forebrain CBF was measured with [3H]nicotine. One group of animals did not undergo hemodilution and served as controls (Con). In the three experimental groups, hematocrit was reduced from 44% to 17-19%. Con and hemodiluted (HDil) groups were ventilated with 40% O2 at 101 kPa (1 atmosphere absolute), which resulted in CaO2 values of 19.7 +/- 1.3 and 8.1 +/- 0.7 (SD) ml O2/dl, respectively. A second group of hemodiluted animals (HBar) was ventilated with 100% O2 at 506 kPa (5 atmospheres absolute) in a hyperbaric chamber, which restored CaO2 to an estimated 18.5 +/- 0.5 ml O2/dl by increasing dissolved O2. A fourth group of hemodiluted animals (HCon) served as hyperbaric controls and were ventilated with 10% O2 at 506 kPa, resulting in CaO2 of 9.1 +/- 0.6 ml O2/dl. CBF was 79 +/- 19 ml. 100 g-1. min-1 in the Con group and significantly increased to 123 +/- 9 ml. 100 g-1. min-1 in the HDil group. When CaO2 was restored to baseline with dissolved O2 in the HBar group, CBF decreased to 104 +/- 20 ml. 100 g-1. min-1. When normoxia was maintained during hyperbaric exposure in the HCon group, CBF was 125 +/- 18 ml. 100 g-1. min-1, a value indistinguishable from that in normobaric HDil animals. Our data demonstrate that the reduction in CaO2 after hemodilution is responsible for 40-60% of the increase in CBF.