Seiji Takaoka

Interactions between Hypothermia and the Latency to Ischemic Depolarization Implications for Neuroprotection

Background The authors postulated that hypothermic neuroprotection can be attributed to a delayed onset of ischemic depolarization. Methods Halothane‐anesthetized rats were prepared for near‐complete forebrain ischemia. Direct current (DC) potential microelectrodes were placed in hippocampal CA1. The pericranial temperature was maintained at 31 [degree sign] Celsius, 33 [degree sign] Celsius, 35 [degree sign] Celsius, or 37 [degree sign]C (n = 6 per group). Bilateral carotid occlusion with systemic hypotension was initiated for 10 min. The time to onset of the DC shift was recorded. In a second experiment, rats were assigned to 37 [degree sign]C or 31 [degree sign]C for 10 min of ischemia, or to 31 [degree sign]C for 14 min of ischemia (n = 8 per group). These durations of ischemia were defined to allow 9 min of ischemic depolarization in the 37 [degree sign] Celsius‐10 min and 31 [degree sign] Celsius‐14 min groups. Neurologic and histologic outcomes were examined 7 days later. Results Hippocampal CA1 time to depolarization increased with decreasing temperature (P < 0.0001). Time to depolarization was increased by approximately 4 min in the rats maintained at 31 [degree sign]C compared with those at 37 [degree sign] Celsius. Time to repolarization during reperfusion was not affected by temperature. Increasing the duration of ischemia from 10 min to 14 min with the pericranial temperature maintained at 31 [degree sign]C resulted in a duration of depolarization that was equivalent in the 37 [degree sign] Celsius‐10 min and 31 [degree sign] Celsius‐14 min groups. However, hippocampal CA1 damage was not increased (31 [degree sign] Celsius‐10 min = 4 +/‐ 1% dead neurons; 31 [degree sign] Celsius‐14 min = 6 +/‐ 1% dead neurons, 95% CI, ‐1% to 3%; 37 [degree sign] Celsius‐10 min = 90 +/‐ 17% dead neurons). Conclusions Despite similar durations of DC depolarization, outcome in hypothermic rats was markedly improved compared with normothermic rats. This indicates that hypothermic neuroprotection can be attributed to mechanisms other than the delay in time to onset of ischemic depolarization.

The Dose-Dependent Effects of Isoflurane on Outcome from Severe Forebrain Ischemia in the Rat

Isoflurane improves outcome against cerebral ischemia in the rat. However, the optimal neuroprotective concentration has not been defined. We examined the effects of different isoflurane concentrations on outcome from severe forebrain ischemia in the rat. Fasted rats were subjected to 0.5, 1.0, 1.5, 2.0, or 2.5 minimum alveolar concentration (MAC) isoflurane during 10 min bilateral carotid occlusion plus systemic hypotension. Each isoflurane concentration was administered only before ischemia. Arterial blood pressure was not pharmacologically manipulated. After ischemia, the anesthetic regimen was changed to fentanyl/nitrous oxide and maintained for 2 h. Pericranial temperature was maintained normothermic during the experiment. Neuromotor score, % dead hippocampal CA1 neurons, and cortical injury were measured 5 days postischemia. Preischemic arterial blood pressure decreased as MAC was increased. Animals administered >1.0 MAC frequently exhibited postischemic seizures resulting in increased mortality. There was no difference among MAC conditions for % dead CA1 neurons (93 ∼ 95%). In the cortex, neuronal necrosis was less severe with 0.5 MAC and 1.0 MAC isoflurane relative to >1.0 MAC values. The neuromotor score in the 1.0 MAC isoflurane group was superior to the 2.5 MAC group. Dose-dependent effects of preischemic administration of isoflurane on histologic and behavioral outcome after severe forebrain ischemia were observed. Isoflurane MAC values <1.5 provided superior overall outcome relative to larger isoflurane concentrations.

Neuroprotective Effect of NMDA Receptor Glycine Recognition Site Antagonism Persists When Brain Temperature is Controlled

Several lines of inquiry have indicated that glycine plays an important role in both glutamatergic neurotransmission and pathophysiology of cerebral ischemia. However, subacute outcome trials demonstrating the efficacy of glycine antagonists as neuroprotectants have not been performed with rigorous control of brain temperature. In this study, we investigated the effect of N-methyl-D-aspartate (NMDA) receptor glycine recognition site antagonism in a temperature-controlled rodent model of transient focal ischemia. Male Wistar rats underwent 75 min of intraluminal middle cerebral artery occlusion (MCAO). During MCAO and the first 24 h of reperfusion, rats (n = 10) were administered either vehicle or the glycine antagonist 5-nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA 1021) i.v. as a bolus infusion of 5 mg/kg followed by 3.5 mg/kg/h (Low-Dose) or 10 mg/kg followed by 7 mg/kg/h (High-Dose) for 24 h. Cortical temperature was controlled at 38.0 ± 0.1°C during MCAO and the first 6 h of reperfusion. A 7-day recovery interval was allowed. Mean total infarct volume was reduced by ∼ 40% in both high- and low-dose groups (p < 0.01). The preponderance of infarct reduction occurred in the cortex (p < 0.01). Neurologic function correlated with the size of cerebral infarct (p = 0.001). Neurologic grade was similarly improved by treatment with either dose (p = 0.01). These results demonstrate that neuroprotection achieved by antagonism of the glycine recognition site persists when brain temperature is controlled, indicating a potent mechanism of action other than attenuating a hyperthermic response to ischemia.

Hypothermia reduces the propensity of cortical tissue to propagate direct current depolarizations in the rat

Both spreading depression (SD) and spontaneous cortical ischemic depolarizations are known to be sensitive to brain temperature. What is unknown is whether this temperature effect is caused by altered sensitivity of cortical tissue to the initiating stimulus or is attributable to an altered ability of cortex to propagate the depolarization wave. To address this, halothane anesthetized rats underwent surface heating/cooling to produce pericranial temperatures of 33 degrees C, 38 degrees C, or 40 degrees C. Spreading depression was first initiated by electrocortical stimulation and then by topical application of KCl. The electrical threshold for SD and the time to direct current shift onset after KCl administration were unaffected by temperature. In contrast, the ability of cortical tissue to propagate the SD wave was temperature dependent. Decreasing temperature from 40 degrees C to 33 degrees C was associated with a slowing of the rate of propagation by 25-30% while the duration of the propagated direct current (DC) shifts was increased by 80% regardless of the initiating stimulus. After elicitation of persistent local DC shift with KCl, the interval between initial waves of SD was progressively increased as temperature was decreased. For either method of stimulation, once SD was initiated, the amplitude of the waveform was temperature independent. These results confirm the importance of temperature regulation in procedures examining SD in vivo. Further, temperature effects on SD reflect propensity of the tissue to propagate depolarization waves although ability of cortex to depolarize in direct response to the stimulus does not undergo substantive change.

Influence of Carbon Dioxide on Respiratory Function during Posterior Retroperitoneoscopic Adrenalectomy in Prone Position

Objective: To evaluate the influences of CO₂ insufflation on changes in blood gas analysis and end tidal CO₂ tension (PetCO₂) during posterior retroperitoneoscopic adrenalectomy in the prone position. Methods: Arterial blood gas analysis and measurements of PetCO₂ were carried out during CO₂ insufflation in 16 patients who underwent posterior retroperitoneoscopic adrenalectomy in the prone position (PRA group). The results were compared to 10 patients who underwent open posterior adrenalectomy (OPA group). Ventilation was artificially controlled during the study period in all cases. Results: Arterial pH, PaCO₂, PetCO₂ and PaO₂ were not significantly different between the PRA and OPA groups. However, the PaCO₂–PetCO₂ gradient in the PRA group was significantly higher than that in the OPA group (p < 0.01). Conclusion: Transperitoneal absorption of CO₂ occurs in patients undergoing retroperitoneoscopy in the prone position. The alveolo-arterial CO₂ gradient may be the only parameter which indicates the absorption of CO₂ during PRA.

Perioperative management of lobectomy in a patient with hypertrophic obstructive cardiomyopathy treated with dual-chamber pacing

previously. A routine chest roentgenogram taken during an annual check-up showed a suspicious shadow. The patient was referred to another hospital for a complete medical evaluation. Left lung cancer was diagnosed. His electrocardiogram (ECG) showed a negative T wave in leads V5 and V6, indicating a pattern of old septal and inferior myocardial infarction with mild left ventricular (LV) hypertrophy. Furthermore, epicardial echocardiography (EE) revealed interventricular septal hypertrophy (ISH) and LV outflow hypertrophy, without deterioration of LV wall motion but with mild mitral regurgitation (MR). His cardiac index (CI), ejection fraction (EF), and EE-derived LV-Ao PG were 3.85 l·min 1·m 2, 86%, and 72 mmHg, respectively. Finally, HOCM accompanied with MR were diagnosed. The patient was scheduled for right upper lobectomy in the same hospital without any specific medical treatment for HOCM prior to surgery. The patient was premedicated with intramuscular atropine (0.5 mg) and hydroxyzine (50mg) prior to the induction of anesthesia. On arrival at the operating theater, his heart rate was 78 beats·min 1, and his systolic and diastolic blood pressure showed 132/86mmHg. After the placement of an epidural catheter via the thoracic segment T8/9, anesthesia was induced with bolus intravenous (iv) fentanyl (0.8μg·kg 1) and propofol (1mg·kg 1), as well as with continuous infusion of propofol (10mg·kg 1·h 1), followed by vecuronium (0.03 mg·kg 1). Hypotension (60 mmHg) and profound bradycardia (35 beats·min 1) were observed after anesthesia was induced. Hypotension was controlled rapidly both by volume replacement and intermittent administration of bolus iv methoxamine (1mg), whereas bradycardia persisted at less than 40 beats·min 1. The anesthetists discontinued the induction of anesthesia and cancelled the operation. Ten minutes later, the heart rate of the patient gradually recovered to a level of 50 beats·min 1. Oral atenolol (50mg·day 1) and disopyramide (300 mg·day 1) were started immediately

Glycine antagonism does not block ischemic spontaneous depolarization in the rat

THIS study examined the effect of glycine recognition site antagonism (ACEA 1021) on the incidence of spontaneous depolarizations in the penumbra of a focal ischemic lesion. Rats were administered either vehicle (n = 7), ACEA 1021 (n = 7) or dizocilpine (n = 5) and then underwent 90 min middle cerebral artery occlusion. The cortical direct current (DC) potential was recorded. During ischemia, 7 ± 3 DC shifts occurred in the vehicle group. ACEA 1021 did not reduce this frequency (7 ± 2 DC shifts) although dizocilpine did (1 ± 1 DC shifts; p = 0.02). The previously demonstrated neuro-protective property of ACEA 1021 during focal cerebral ischemia cannot be attributed to reduction of spontaneous depolarization in the ischemic penumbra.

Cardiac arrest following induction of anesthesia in a patient with acute massive pulmonary thromboembolism

Patients with massive pulmonary thromboembolism (PE) occasionally develop acute right ventricular dysfunction followed by circulatory collapse or sudden death. Early diagnosis and aggressive treatment of this condition are therefore essential [1]. The present report is a case of cardiac arrest following induction of anesthesia for pulmonary thrombectomy in a patient with acute massive PE after lobectomy.

A comparison of sympathetic adrenal nerve responses to intravenous high-dose morphine and fentanyl administration in rats.

We compared the effects of intravenous morphine (5 mg·kg−1) and fentanyl, (50μg·kg−1) on systolic blood pressure (SBP), heart rate (HR), and efferent sympathetic adrenal nerve action potentials (SANA) in rats. We also determined the extent of the reflex responses of these parameters of 9% carbon dioxide (CO2) challenge during the above narcotic anesthesia. In the morphine group, SBP was elevated and the elevated levels were maintained, while changes in SBP in the fentanyl group were not significant. In the morphine group, SANA showed initial stimulation and subsequent depression, while in the fentanyl group, SANA showed sustained depression. CO2 challenge induced only very small changes in SBP and HR, suggesting that during high-dose narcotic anesthesia the hypercapnic stimulus may not be reflected in circulatory parameters. In both groups, hypercapnia increased SANA to 30% of the baseline values from the pre-challenge level. However, these values were only 91% and 56% of the baseline value in the morphine and the fentanyl, groups, respectively.

Effects of halothane and isoflurane anesthesia on sympathetic adrenal nerve responses to carbon dioxide challenge in rats.

We studied the influence of two volatile anesthetics, halothane and isoflurane, on the circulatory and sympathetic nerve responses to carbon dioxide (9% CO2) in rats.Systolic blood pressure was depressed throughout the CO2 challenge and after an initial reduction, a gradual increase was observed in heart rate. Sympathetic adrenal nerve action potentials (SANA) significantly increased in contrast to negative responses in the circulatory functions. SANA responses against time were trapezoid in shape. There were no significant differences in SANA responses between 1%(1 MAC) and 1.5%(1.5 MAC) halothane groups, nor between 1.4%(1 MAC) and 2%(1.5 MAC) isoflurane groups. Halothane and isoflurane, therefore, did not produce dose-dependent effects on sympathetic response to hypercapnia within these concentrations. The maximum changes in SANA from the baseline values were 110% and 40% for the halothane and isoflurane groups, respectively.The sympathetic reflex response to hyperacapnia was retained at 1.5 MAC for both anesthetics, though isoflurane depressed these responses more markedly than halothane.Our results suggest that halothane is a more preferable anesthetic than isoflurane when viewed from the standpoint of preservation of sympathetic nerve response in such undesirable situations as severe hypercapnia occurring during anesthesia.