Sachiyo Sakamoto

Effect of propofol and isoflurane anaesthesia on the immune response to surgery.

There are two major subpopulations of peripheral helper T lymphocytes: T helper 1 (Th1) and T helper 2 (Th2) cells. Surgical stress increases the number of Th2 cells, and decreases that of Th1 cells, resulting in a decrease in the Th1/Th2 ratio, and, consequently, in suppressed cell‐mediated immunity. Since anaesthesia can suppress the stress response to surgery, it may inhibit the decrease in the Th1/Th2 ratio. Using flow cytometry, we studied whether propofol anaesthesia (n = 9) or isoflurane anaesthesia (n = 9) had more effect on the decrease in the Th1/Th2 ratio after surgery in patients undergoing craniotomy. The Th1/Th2 ratio decreased significantly after isoflurane anaesthesia (p = 0.011), while it did not change after propofol anaesthesia. The ratio was significantly lower with isoflurane than propofol (p = 0.009). Propofol anaesthesia attenuated the surgical stress‐induced adverse immune response better than isoflurane anaesthesia.

Edaravone, a free radical scavenger, mitigates both gray and white matter damages after global cerebral ischemia in rats.

Recent studies have shown that similar to cerebral gray matter (mainly composed of neuronal perikarya), white matter (composed of axons and glias) is vulnerable to ischemia. Edaravone, a free radical scavenger, has neuroprotective effects against focal cerebral ischemia even in humans. In this study, we investigated the time course and the severity of both gray and white matter damage following global cerebral ischemia by cardiac arrest, and examined whether edaravone protected the gray and the white matter. Male Sprague-Dawley rats were used. Global cerebral ischemia was induced by 5 min of cardiac arrest and resuscitation (CAR). Edaravone, 3 mg/kg, was administered intravenously either immediately or 60 min after CAR. The morphological damage was assessed by cresyl violet staining. The microtubule-associated protein 2 (a maker of neuronal perikarya and dendrites), the beta amyloid precursor protein (the accumulation of which is a maker of axonal damage), and the ionized calcium binding adaptor molecule 1 (a marker of microglia) were stained for immunohistochemical analysis. Significant neuronal perikaryal damage and marked microglial activation were observed in the hippocampal CA1 region with little axonal damage one week after CAR. Two weeks after CAR, the perikaryal damage and microglial activation were unchanged, but obvious axonal damage occurred. Administration of edaravone 60 min after CAR significantly mitigated the perikaryal damage, the axonal damage, and the microglial activation. Our results show that axonal damage develops slower than perikaryal damage and that edaravone can protect both gray and white matter after CAR in rats.

Sevoflurane causes greater QTc interval prolongation in elderly patients than in younger patients.

BACKGROUND: Sevoflurane and droperidol prolong the QT interval, and advancing age is not only associated with a prolongation of the QT interval but is also a risk factor for drug-induced QT interval prolongation. In this study, we compared the effect of sevoflurane and droperidol on the corrected QT (QTc) interval and the dispersion of ventricular repolarization (time interval from the peak to the end of the T wave [Tp-e]) in elderly patients with those in younger patients. METHODS: Under sevoflurane anesthesia (1.5%–2.5%) with an antiemetic dose of droperidol (1.25 mg), the QT interval and the Tp-e interval, which indicates transmural dispersion of repolarization across the myocardial wall, were measured in 30 elderly patients (70 years and older) and in 30 younger patients (20–69 years) for 2 hours. The QT interval was normalized for heart rate (QTc) using 3 different formulas: Bazett, Matsunaga, and Van de Water. Data are presented as mean ± sd. RESULTS: The elderly group was 24.4 years older (P < 0.05) than the younger group. The QTc intervals in the 2 groups before anesthesia were not significantly different. Using all 3 formulas, the QTc interval in the elderly patient group was significantly prolonged by sevoflurane (the QTc intervals at preanesthesia and 60, 75, 90, and 120 minutes after sevoflurane exposure were 0.434 ± 0.028 seconds, 0.450 ± 0.037 seconds, 0.463 ± 0.037 seconds, 0.461 ± 0.037 seconds, and 0.461 ± 0.038 seconds, respectively, with the Bazett formula). The sevoflurane-induced QTc interval prolongation in the elderly patient group was significantly greater than that in the younger patient group (0.450 ± 0.037 seconds vs 0.432 ± 0.034 seconds, 60 minutes after sevoflurane exposure; 0.463 ± 0.037 seconds vs 0.441 ± 0.037 seconds, 75 minutes after sevoflurane exposure; and 0.461 ± 0.038 seconds vs 0.436 ± 0.030 seconds, 120 minutes after sevoflurane exposure with the Bazett formula), but the sevoflurane-induced QTc interval prolongation was neither further enhanced with time nor by droperidol. The Tp-e interval was not affected in either group. CONCLUSION: Sevoflurane causes greater QTc interval prolongation in elderly patients than in younger patients. Although sevoflurane does not affect the transmural dispersion of repolarization and sevoflurane-induced QTc prolongation does not advance with time and by droperidol administration, QT interval prolongation and its associated arrhythmias should be carefully monitored during sevoflurane anesthesia in elderly patients.

The differential effects of nitrous oxide and xenon on extracellular dopamine levels in the rat nucleus accumbens: a microdialysis study.

Dopamine release in the nucleus accumbens (NAC) plays a crucial role in the action of various psychotropic and addictive drugs, such as antagonists of the N-methyl-d-aspartate subtype of the glutamate. Although both nitrous oxide and xenon are N-methyl-d-aspartate receptor antagonists, they differ in their potential for producing neuropsychological toxicity; therefore, we decided to examine their effects on both spontaneous and ketamine-induced extracellular dopamine levels in the NAC. A microdialysis probe was implanted into the NAC in each of 35 rats, which were randomly assigned to one of six groups: exposure to 40% O2, exposure to 60% nitrous oxide (0.27 MAC), exposure to 43% xenon (0.27 MAC) for 60 min, and three groups exposed to either 40% O2, 60% nitrous oxide, or 43% xenon for 70 min and 80 mg/kg ketamine was given i.p. 10 min after the initiation of gas exposure. Perfusate samples were collected every 20 min, and the dopamine levels were measured using a high-performance liquid chromatography system. Nitrous oxide, but not xenon, significantly increased the dopamine level. Ketamine significantly increased the dopamine level, and this was significantly inhibited by xenon, but not by nitrous oxide. These data suggest that the difference in neuropsychological activity between nitrous oxide and xenon is partly due to their differential effects on the mesolimbic dopamine system.

Ketamine attenuates hypocapnia-induced neuronal damage in the caudoputamen in a rat model of chronic cerebral hypoperfusion

We previously demonstrated that the caudoputamen was exclusively further damaged by hypocapnia in a rat with chronic cerebral hypoperfusion which is characterized by white matter lesions (WML) and a well-established model for patients with cerebrovascular diseases and/or dementia, and suggest that this process may be the cause of long lasting postoperative delirium or brain dysfunction in such patients. In the present study, we investigated whether ketamine, a non-competitive N-methyl-D-aspartate receptor antagonist, could attenuate the neuronal damage in the caudoputamen. Ketamine, at doses of 10 and 20 mg/kg, which was given intraperitoneally before hypocapnia induction, attenuated the aggravation of WML score, neuronal damage, and astroglial proliferation in the rat caudoputamen. These results suggest that ketamine may be beneficial for preventing postoperative brain dysfunction, especially in patients with cerebrovascular diseases and/or dementia induced by hypocapnia, which is likely to occur in the mechanical ventilation used during surgery.