Murray P A, Blanck T J, Rogers M C, Jacobus W E
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205.
Anesthesiology. 1987 Nov;67(5):649-53. doi: 10.1097/00000542-198711000-00006.
Utilizing 31phosphorus nuclear magnetic resonance (NMR) spectroscopy, the authors tested the two hypotheses that the negative inotropic action of halothane is the result of: 1) myocardial intracellular acidosis, and 2) a decrease in myocardial high-energy phosphates. In isolated, paced, Langendorff-perfused rabbit hearts, halothane (1.5 vol %) dissolved in the coronary perfusate produced a 48 +/- 2% decrease (P less than 0.01) in left ventricular developed pressure. In contrast, halothane administration had no significant effect on myocardial intracellular pH (7.18 +/- 0.04 at control vs 7.21 +/- 0.02 during halothane). Halothane exposure decreased (P less than 0.01) the forward rate constant of the creatine kinase reaction by 32 +/- 6%, as measured using saturation transfer NMR, suggesting a decline in the rate of high-energy phosphate metabolism. This was further indicated by a concomitant decrease (P less than 0.05) in myocardial oxygen consumption (20 +/- 5%). During the halothane-induced reduction in left ventricular developed pressure, only small decreases in the myocardial steady state concentrations of phosphocreatine (7 +/- 1%; P less than 0.01) and beta ATP (12 +/- 4%; P less than 0.05), and an increase in Pi (18 +/- 6%; P less than 0.05) were observed. However, similar changes in steady-state high-energy phosphate metabolites were also measured in time-control hearts not exposed to halothane. These results indicate that the negative inotropic action of halothane is not mediated by myocardial intracellular acidosis. Moreover, these findings do not support the concept that the negative inotropic action of halothane is the result of a reduction in myocardial high-energy phosphates.
作者利用31磷核磁共振（NMR）光谱法，检验了两个假说：1）氟烷的负性肌力作用是心肌细胞内酸中毒的结果；2）心肌高能磷酸盐减少。在离体、起搏、Langendorff灌注的兔心脏中，溶解于冠状动脉灌注液中的氟烷（1.5体积%）使左心室舒张末压降低了48±2%（P<0.01）。相比之下，给予氟烷对心肌细胞内pH无显著影响（对照时为7.18±0.04，氟烷给药期间为7.21±0.02）。使用饱和转移NMR测量，氟烷暴露使肌酸激酶反应的正向速率常数降低了32±6%（P<0.01），提示高能磷酸盐代谢速率下降。心肌耗氧量随之降低（20±5%）（P<0.05）进一步证明了这一点。在氟烷诱导左心室舒张末压降低期间，仅观察到磷酸肌酸的心肌稳态浓度小幅降低（7±1%；P<0.01）、β-ATP小幅降低（12±4%；P<0.05）以及无机磷增加（18±6%；P<0.05）。然而，在未暴露于氟烷的时间对照心脏中也测量到了稳态高能磷酸盐代谢物的类似变化。这些结果表明，氟烷的负性肌力作用不是由心肌细胞内酸中毒介导的。此外，这些发现不支持氟烷的负性肌力作用是心肌高能磷酸盐减少的结果这一概念。
