Shiro Tomiyasu

Sevoflurane protects stunned myocardium through activation of mitochondrial ATP-sensitive potassium channels

We sought to determine the hemodynamic and cardioprotective effects of sevoflurane in canine stunned myocardium. Forty-nine dogs were allocated to one of seven groups (n = 7 for each). In six separate groups, dogs received vehicle, glibenclamide (a nonselective adenosine triphosphate-dependent potassium [KATP] channel antagonist) (0.3 mg/kg IV) or 5-hydroxydecanoic acid (a mitochondrial KATP channel antagonist) (5 mg/kg IV) in the presence or absence of 1 minimum alveolar concentration (1 MAC) sevoflurane. In an additional group, dogs received 1 MAC sevoflurane with hemodynamic correction. Regional myocardial contractility was evaluated with segment shortening. Measurements were made before and during 15-min ischemia and 90-min reperfusion. Recovery of segment shortening 90 min after reperfusion was significantly improved in the dogs anesthetized with sevoflurane either with or without hemodynamic correction (70.1 ± 4.2 and 75.9 ± 3.1% of baseline, respectively), whereas the recovery was poor in control and glibenclamide or 5-hydroxydecanoic acid pretreated dogs (33.3 ± 4.3, 33.8 ± 6.8, and 45.0 ± 5.5% of baseline, respectively). Regional myocardial perfusion showed no significant difference among groups. The results indicate that sevoflurane has a cardioprotective effect mediated through activation of mitochondrial KATP channels and independent of coronary blood flow or reduction in cardiac work.

The effects of dexmedetomidine on left ventricular function during hypoxia and reoxygenation in isolated rat hearts.

Hypoxia resulting from apnea in patients with sleep apnea is an important factor in heart disease. We designed the present study to determine whether dexmedetomidine (DEX) has a direct protective effect against hypoxia-reoxygenation-induced left ventricular dysfunction without systemic hemodynamic and humoral effects. Isolated rat hearts were exposed to 60-min hypoxia followed by 30-min reoxygenation with 0, 10, or 100 nM DEX prehypoxia administration (n = 7 each group). In a second experiment (n = 7), 100 nM DEX was administered posthypoxia. In a third experiment (n = 7 each group), an &agr; 2 antagonist, yohimbine was given with and without 100 nM DEX prehypoxia administration. DEX prehypoxia, but not posthypoxia, administration significantly improved the recovery of left ventricular developed pressure after reoxygenation (0, 10, 100 nM DEX prehypoxia or 100 nM DEX posthypoxia values were 53 ± 6, 64 ± 9, 78 ± 13, or 62 ± 12 mm Hg [mean ± sd]) and reversed by yohimbine, 58 ± 8 mm Hg, respectively. We conclude that DEX exerts the direct protective effect on the left ventricular dysfunction caused by hypoxia-reoxygenation through mainly &agr; 2-adrenergic stimulation before and during the hypoxic period.

Comparative analysis of systemic and coronary hemodynamics during sevoflurane- and isoflurane-induced hypotension in dogs.

We studied the effects of sevoflurane on myocardial contractility and systemic and coronary hemodynamics, as compared with the effects of isoflurane in dogs under the same cardiac work conditions. Sixteen mongrel dogs were anesthetized with alpha-chloralose. Heart was paced at 100 beats/min after producing a complete atrioventricular (A-V) block. Controlled hypotension to a mean arterial pressure (MAP) of 60 mm Hg was induced and maintained by inhalation of either anesthetic, lasting for 60 min. Measurements were made at baseline, 15 min (T1), and 60 min (T2) after starting hypotension, and 30 min after discontinuing equihypotension (T3). Although left ventricular systolic segment shortening (%SS) decreased approximately 20% in both groups, cardiac output (CO) decreased only in sevoflurane during equihypotension (-27.6% at T2). Sevoflurane decreased the coronary blood flow (CBF; -34.8% at T2) with no significant change of coronary vascular resistance (CVR), whereas isoflurane produced a significant decrease in CVR resulting in no change of CBF despite of decreased coronary perfusion pressure (-37.4% at T2). These systemic and coronary vascular effects were continued even at T3. In conclusion, myocardial depressant effects were comparable between sevoflurane and isoflurane. Both systemic and coronary vasodilatory effects of isoflurane are greater than those of sevoflurane.

Evaluation of allodynia and pain associated with postherpetic neuralgia using current perception threshold testing.

ObjectivesPostherpetic neuralgia has various clinical features, and the implicated pathophysiologic mechanisms are controversial. This study was carried out to clarify the roles of peripheral sensory nerves in the production of allodynia and ongoing pain. Current perception threshold (CPT) testing was used to evaluate the sensory function. MethodsThe intensities of ongoing pain and dynamic allodynia were assessed using a numeric rating scale (0–10). Assessment of sensory nerve function was performed by a series of 2,000-, 250-, and 5-Hz stimuli using CPT testing. These measurements were made in ipsilateral and contralateral area. ResultsCPTs at all frequencies in the ipsilateral area were significantly higher than those in the contralateral area. There were significant and inverse correlations between the intensity of allodynia and CPTs at all frequencies. No correlation was found between the intensity of ongoing pain and CPTs at any frequency. There was no correlation between the intensity of ongoing pain and the intensity of dynamic allodynia. ConclusionsThe intensity of dynamic allodynia in postherpetic neuralgia correlates with the preserved functions of Aβ, Aδ, and C fibers. In contrast, the intensity of ongoing pain does not correlate with either the preserved function of C fibers or the intensity of dynamic allodynia. Therefore, it is suggested that postherpetic neuralgia might be a pain syndrome including both peripheral and central mechanisms.

Cardioprotective effects of KB-R7943, a novel inhibitor of Na+/Ca2+ exchanger, on stunned myocardium in anesthetized dogs.

PurposeThe present study was carried out to determine the cardioprotective effects of KB-R7943 (KBR), a selective inhibitor of the reverse mode of Na+/Ca2+ exchanger (NCX), on stunned myocardium in anesthetized dogs.MethodsThe dogs were allocated to one of three groups (n = 7 for each group), and received drug vehicle (group C), low-dose KBR (5 mg·kg−1 i.v.) (group L) or high-dose KBR (10 mg·kg−1 i.v.) (group H) at 15 min before left anterior descending coronary artery (LAD) occlusion. Stunned myocardium was produced by 15-min occlusion of LAD and 90-min reperfusion in all dogs. Regional myocardial contractility was evaluated with segment shortening (%SS).ResultsRecovery of %SS at 90 min after reperfusion was significantly improved in group H (70.8% ± 3.9% of baseline), whereas the recovery was poor in groups C and L (34.3% ± 2.8% and 36.4% ± 5.4% of baseline, respectively). Regional myocardial blood flow showed no significant difference among groups. KBR had no effect on coronary or systemic hemodynamics.ConclusionThe results show that preischemic administration of high-dose KBR markedly improves myocardial contractile dysfunction after ischemia-reperfusion in anesthetized dogs, indicating that KBR protects myocardium against the ischemia-reperfusion injury in vivo.

Multiple sclerosis with severe pain and allodynia alleviated by oral ketamine.

The objective of this study is to determine the effect of oral ketamine on pain and allodynia associated with multiple sclerosis. A 60-year-old woman with multiple sclerosis was referred to our clinic because of severe pain and allodynia. Oral ketamine was started at a dose of 20 mg once a day and increased to twice a day. Oral ketamine was effective in the treatment of the pain and allodynia associated with multiple sclerosis.

Carbachol, norepinephrine, and hypocapnia stimulate phosphatidylinositol turnover in rat tracheal slices.

Background The intracellular mechanisms involved in the alpha‐adrenoceptor‐ or hyperventilation‐induced bronchoconstriction remain unknown. Because there is a direct relationship between phosphatidylinositol (PI) metabolism and airway smooth muscle contraction induced by muscarinic agonists, the authors examined the effects of carbachol (CCh), norepinephrine (NE), and hypocapnia on PI turnover in the airway smooth muscle. Methods Rat tracheal slices were incubated in Krebs‐Henseleit solution containing LiCl and [sup 3 Hydrogen]myo‐inositol in the presence of NE, CCh, or neither. The PCO2 in the solution was 36 plus/minus 3 mmHg (normocapnia), 19 plus/minus 2 mmHg (moderate hypocapnia), or 5 plus/minus 2 mmHg (severe hypocapnia), respectively. [sup 3 Hydrogen]inositol monophosphate (IP1) formed was counted with a liquid scintillation counter. Results Basal IP1 formed was greater at severe hypocapnia than at normocapnia. Norepinephrine‐ and CCh‐induced IP1 formation were also greater at hypocapnia than at normocapnia. Conclusions These results indicate that CCh, NE, and hypocapnia stimulate PI turnover in the airway smooth muscle, which would cause bronchoconstriction, and hypocapnia also augments NE‐ and CCh‐induced PI turnover, which could cause worsening of exercise‐induced asthma and vagotonic asthma, respectively.

Pneumothorax associated with epidural anesthesia.

paramedian approach at the level of the Th7–Th8 interspace. After contacting the vertebral lamina, the angle of the needle was adjusted to identify the epidural space. The Tuohy needle was directed at an angle of 45° to cephalad, and, presumably, less than 15° toward the midline. A loss-of-resistance technique, using a salinefilled glass syringe, detected a likely space at a depth of 6 cm from the skin. A test aspiration was done with the syringe to confirm negative blood or cerebrospinal fluid, when air was aspirated unexpectedly. At that moment, the patient leaned slightly toward the resident. Although no symptom of pneumothorax, such as respiratory distress or decreased breath sounds, was observed, the needle was withdrawn. The other, experienced, anesthesiologist tried to insert the epidural needle via the left paramedian approach at the level of the Th8–Th9 interspace after adjusting the patient’s position, but without changing it to another position. The Tuohy needle was introduced 1.0 cm laterally from the midline. After contacting the lamina, “walking” on the lamina facilitated the loss-of-resistance feeling obtained at a depth of 6cm from the skin. The angle of the needle was then about 45° to cephalad, and 15° toward the midline. A test dose of 3 ml of 2% lidocaine was injected from the epidural catheter. Bilateral Th7–Th9 thermal hypesthesia was confirmed 5min later with cold test. Subsequently, general anesthesia was induced with intravenous fentanyl, 100 μg; propofol, 90 mg; and vecuronium, 9 mg. To achieve left-sided one-lung ventilation during the right bullectomy, a single-lumen endotracheal tube with a bronchial blocker was intubated. Anesthesia during one-lung ventilation was maintained with sevoflurane, 70% oxygen in nitrogen and intravenous fentanyl, and appropriate oxygenation and carbon dioxide elimination were maintained. The anesthesia and operative procedure were then uneventful. A routine postoperative chest radiograph, to verify proper pulmonary expansion, was taken about 4h after the first attempt at inserting the epidural catheter, and it

Effect of ONO-1101, a novel short-acting β-blocker on hemodynamic responses to isoflurane inhalation and tracheal intubation

PurposeWe investigated the effect of a new ultrashort-acting β-blocker, ONO-1101, on hemodynamic responses to isoflurane inhalation and tracheal intubation.MethodsFifty-four ASA PS 1 or 2 patients were randomly allocated to receive either ONO-1101, 0.04 mg·kg−1·min−1, or saline prior to tracheal intubation. Anesthesia was induced with thiamylal, 4 mg·kg−1, and vecuronium, 0.15 mg·kg−1. Tracheal intubation was carried out after 3 min controlled mask ventilation with 66% N2O and 3% inspired isoflurane in oxygen. Heart rate and blood pressure were continuously recorded from the start of induction until 5 min after intubation. Plasma concentrations of catecholamines were measured before induction, 3 min after initiating inhalation of isoflurane, and 1 min after tracheal intubation.ResultsSignificant increases in heart rate occurred in both groups in response to isoflurane inhalation and tracheal intubation, but the magnitude of the increase was significantly less in the ONO-1101 group. Blood pressure increased after tracheal intubation in the saline group but remained unchanged in the ONO-1101 group. Plasma concentrations of norepinephrine increased after induction and intubation in both groups, with no significant difference between the groups.ConclusionONO-1101 infusion is effective for the attenuation of hemodynamic responses to isoflurane inhalation and tracheal intubation.

Epidural ropivacaine infusion for the treatment of pain following axillary muscle-sparing thoracotomy: a dose-evaluation study

PurposeWe aimed to investigate the optimal dose of continuous epidural ropivacaine for effective analgesia with minimal side effects after axillary muscle-sparing thoracotomy.MethodsSixty patients undergoing thoracic surgery via the axillary approach were studied. Patients were given continuous epidural ropivacaine at 6 (group R-6), 9 (group R-9), 12 (group R-12) or 18 mg·h−1 (group R-18) in a randomized double-blinded fashion after surgery. All of the patients received nonsteroidal anti-inflammatory drugs (NSAIDs) every 6 h for 24 h postoperatively. Pain intensity was assessed under three conditions (at rest, on moving, and while coughing), at 4, 8, 16, 24, and 48 h after surgery, and the extent of sensory block was evaluated at the same time points. The ability of a patient to walk unaided was assessed at 24 and 48 h after surgery.ResultsPain intensity at rest and coughing was significantly higher in group R-6 than in the other groups at 16 h after surgery. Pain intensity during moving was significantly greater in group R-6 than in groups R-12 and R-18 at 16 h after surgery. Group R-18 exhibited a significantly greater extent of sensory block than the other groups. The number of patients who were not able to walk unaided 24 h after surgery was significantly greater in group R-18. There were no significant differences in the incidences of side effects among the groups.ConclusionOur results showed that epidural analgesia using ropivacaine, at 12 mg·h−1, provided the best analgesia with few side effects.