Stowe D F, Rehmert G C, Kwok W M, Weigt H U, Georgieff M, Bosnjak Z J
Department of Anesthesiology, Cardiovascular Research Center, Medical College of Wisconsin, 53226, USA.
Anesthesiology. 2000 Feb;92(2):516-22. doi: 10.1097/00000542-200002000-00035.
The noble gas xenon (Xe) has been used as an inhalational anesthetic agent in clinical trials with little or no physiologic side effects. Like nitrous oxide, Xe is believed to exert minimal unwanted cardiovascular effects, and like nitrous oxide, the vapor concentration to achieve 1 minimum alveolar concentration (MAC) for Xe in humans is high, i.e., 70-80%. In the current study, concentrations of up to 80% Xe were examined for possible myocardial effects in isolated, erythrocyte-perfused guinea pig hearts and for possible effects on altering major cation currents in isolated guinea pig cardiomyocytes.
Isolated guinea pigs hearts were perfused at 70 mm Hg via the Langendorff technique initially with a salt solution at 37 degrees C. Hearts were then perfused with fresh filtered (40-microm pore) and washed canine erythrocytes diluted in the salt solution equilibrated with 20% O2 in nitrogen (control), with 20% O2, 40% Xe, and 40% N2, (0.5 MAC), or with 20% O2 and 80% Xe (1 MAC), respectively. Hearts were perfused with 80% Xe for 15 min, and bradykinin was injected into the blood perfusate to test endothelium-dependent vasodilatory responses. Using the whole-cell patch-clamp technique, 80% Xe was tested for effects on the cardiac ion currents, the Na+, the L-type Ca2+, and the inward-rectifier K+ channel, in guinea pig myocytes suffused with a salt solution equilibrated with the same combinations of Xe, oxygen, and nitrogen as above.
In isolated hearts, heart rate, atrioventricular conduction time, left ventricular pressure, coronary flow, oxygen extraction, oxygen consumption, cardiac efficiency, and flow responses to bradykinin were not significantly (repeated measures analysis of variance, P>0.05) altered by 40% or 80% Xe compared with controls. In isolated cardiomyocytes, the amplitudes of the Na+, the L-type Ca2+, and the inward-rectifier K+ channel over a range of voltages also were not altered by 80% Xe compared with controls.
Unlike hydrocarbon-based gaseous anesthetics, Xe does not significantly alter any measured electrical, mechanical, or metabolic factors, or the nitric oxide-dependent flow response in isolated hearts, at least partly because Xe does not alter the major cation currents as shown here for cardiac myocytes. The authors' results indicate that Xe, at approximately 1 MAC for humans, has no physiologically important effects on the guinea pig heart.
稀有气体氙(Xe)已在临床试验中用作吸入麻醉剂,几乎没有生理副作用。与一氧化二氮一样,人们认为氙对心血管的不良影响极小,并且与一氧化二氮一样,在人类中达到1个最低肺泡浓度(MAC)所需的氙蒸汽浓度很高,即70 - 80%。在本研究中,检测了高达80%的氙浓度对离体的、红细胞灌注的豚鼠心脏可能产生的心肌效应,以及对离体豚鼠心肌细胞中主要阳离子电流变化的可能影响。
最初通过Langendorff技术在70 mmHg压力下,用37℃的盐溶液灌注离体豚鼠心脏。然后分别用新鲜过滤(40微米孔径)并洗涤过的犬红细胞稀释于在氮气中平衡了20%氧气的盐溶液(对照组)、含20%氧气、40%氙和40%氮气(0.5 MAC)或含20%氧气和80%氙(1 MAC)的溶液灌注心脏。用80%的氙灌注心脏15分钟,然后向血液灌注液中注射缓激肽以测试内皮依赖性血管舒张反应。使用全细胞膜片钳技术,检测80%的氙对浸泡于与上述相同氙、氧气和氮气组合平衡的盐溶液中的豚鼠心肌细胞的心脏离子电流、钠、L型钙和内向整流钾通道的影响。
在离体心脏中,与对照组相比,40%或80%的氙对心率、房室传导时间、左心室压力、冠状动脉血流量、氧摄取、氧消耗、心脏效率以及对缓激肽的血流反应均无显著影响(重复测量方差分析,P>0.05)。在离体心肌细胞中,与对照组相比,80%的氙在一系列电压下对钠、L型钙和内向整流钾通道的幅度也无影响。
与碳氢化合物类气态麻醉剂不同,氙不会显著改变任何测量的电、机械或代谢因素,或离体心脏中一氧化氮依赖性血流反应,至少部分原因是氙不会改变此处所示心肌细胞中的主要阳离子电流。作者的结果表明,对于豚鼠心脏,约为人类1 MAC的氙没有生理上重要的影响。