Kehl Franz, Pagel Paul S, Krolikowski John G, Gu Weidong, Toller Wolfgang, Warltier David C, Kersten Judy R
Department of Anesthesiology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Anesth Analg. 2002 Nov;95(5):1162-8, table of contents. doi: 10.1097/00000539-200211000-00006.
The administration of a volatile anesthetic shortly before a prolonged ischemic episode exerts protective effects against myocardial infarction similar to those of ischemic preconditioning. A second window of preconditioning (SWOP) against myocardial infarction can also be elicited by brief episodes of ischemia when this occurs 24 h before prolonged coronary artery occlusion. Whether remote exposure to a volatile anesthetic also causes delayed myocardial protection is unknown. We tested the hypothesis that the administration of isoflurane 24 h before ischemia produces a SWOP against infarction. Barbiturate-anesthetized dogs (n = 25) were instrumented for measurement of hemodynamics, including aortic and left ventricular (LV) pressures and LV +dP/dt(max), and subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size and coronary collateral blood flow were assessed with triphenyltetrazolium chloride staining and radioactive microspheres, respectively. Two groups of dogs received 1.0 minimum alveolar anesthetic concentration isoflurane for 30 min or 6 h that was discontinued 30 min (acute) or 24 h (delayed) before ischemia and reperfusion, respectively. A control group of dogs did not receive isoflurane. Infarct size was 27% +/- 3% of the LV area at risk in the absence of pretreatment with isoflurane. Acute, but not remote, administration of isoflurane reduced infarct size (12% +/- 1% and 31% +/- 3%, respectively). No differences in hemodynamics or transmural myocardial perfusion during or after occlusion were observed between groups. The results indicate that isoflurane does not produce a SWOP when administered 24 h before prolonged myocardial ischemia in vivo.
Isoflurane mimics the beneficial effects of ischemic preconditioning by protecting myocardium against infarction when it is administered shortly before a prolonged ischemic episode. However, unlike ischemic preconditioning, isoflurane does not produce a second window of protection 24 h after administration in dogs.
在长时间缺血发作前不久给予挥发性麻醉剂，可产生与缺血预处理类似的对心肌梗死的保护作用。当在长时间冠状动脉闭塞前24小时发生短暂缺血时，也可引发针对心肌梗死的第二预处理窗口（SWOP）。远程暴露于挥发性麻醉剂是否也会导致延迟性心肌保护尚不清楚。我们测试了在缺血前24小时给予异氟烷可产生针对梗死的SWOP这一假设。用巴比妥类麻醉的犬（n = 25）安装用于测量血流动力学的仪器，包括主动脉和左心室（LV）压力以及LV +dP/dt（max），并进行60分钟的左前降支冠状动脉闭塞，随后再灌注3小时。分别用氯化三苯基四氮唑染色和放射性微球评估心肌梗死面积和冠状动脉侧支血流。两组犬分别在缺血和再灌注前30分钟（急性）或24小时（延迟）接受1.0最低肺泡麻醉浓度的异氟烷30分钟或6小时。一组对照犬未接受异氟烷。在未用异氟烷预处理的情况下，梗死面积为左心室危险区域的27%±3%。急性给予异氟烷可减少梗死面积（分别为12%±1%和31%±3%），但延迟给予则无此效果。两组之间在闭塞期间或之后的血流动力学或透壁心肌灌注方面未观察到差异。结果表明，在体内长时间心肌缺血前24小时给予异氟烷不会产生SWOP。
异氟烷在长时间缺血发作前不久给予时，通过保护心肌免受梗死，模拟了缺血预处理的有益作用。然而，与缺血预处理不同，异氟烷在犬给药24小时后不会产生第二保护窗口。
