Kanaya N, Kawana S, Tsuchida H, Miyamoto A, Ohshika H, Namiki A
Department of Anesthesiology, Sapporo Medical University, School of Medicine, Japan.
Anesth Analg. 1998 Nov;87(5):1041-7. doi: 10.1097/00000539-199811000-00013.
In this study, we compared the direct myocardial depressant effects of sevoflurane, isoflurane, and halothane and determined whether an L-type Ca2+ channel agonist, Bay K 8644, could attenuate the myocardial depression induced by these anesthetics in cultured neonatal rat ventricular myocytes. Ventricular myocytes were obtained from neonatal rats by enzymatic digestion with collagenase and then cultured for 6-7 days. The myocytes were stabilized in serum-free medium, and the spontaneous beating rate and contractile amplitude were measured by using a fiberoptic sensor. Each anesthetic decreased the beating rate and amplitude in a concentration-dependent manner (1%-4% vol/vol) (P < 0.001), with halothane decreasing the beating rate and amplitude the most (P < 0.01). Isoflurane caused larger decreases in the beating rate than sevoflurane at 3% and 4% (P < 0.05). Potency for suppression of contractile amplitude was in the order of halothane > > isoflurane > sevoflurane. However, the myocardial depressant effects of the anesthetics were not different when their concentrations were corrected for minimum alveolar anesthetic concentration values. Bay K 8644 significantly prevented the anesthetic-depressed amplitude (P < 0.05). We conclude that sevoflurane, isoflurane, and halothane have direct myocardial depressant effects on cultured neonatal rat ventricular myocytes and that the reduction of sarcolemmal L-type Ca2+ channel current levels mediates the myocardial depression observed in these immature hearts.
Sevoflurane, isoflurane, and halothane have a direct cardiodepressant effect on cardiac excitation-contraction coupling in the immature heart, which is mediated by an interaction with the L-type Ca2+ channel.
在本研究中，我们比较了七氟烷、异氟烷和氟烷对心肌的直接抑制作用，并确定L型钙通道激动剂Bay K 8644是否能减轻这些麻醉剂在培养的新生大鼠心室肌细胞中引起的心肌抑制。通过用胶原酶进行酶消化从新生大鼠获取心室肌细胞，然后培养6 - 7天。将肌细胞置于无血清培养基中稳定，并用光纤传感器测量自发搏动率和收缩幅度。每种麻醉剂均以浓度依赖性方式（1% - 4%体积/体积）降低搏动率和幅度（P < 0.001），其中氟烷降低搏动率和幅度的程度最大（P < 0.01）。在3%和4%时，异氟烷引起的搏动率下降幅度大于七氟烷（P < 0.05）。抑制收缩幅度的效能顺序为氟烷>>异氟烷>七氟烷。然而，当根据最低肺泡麻醉浓度值校正麻醉剂浓度时，它们的心肌抑制作用并无差异。Bay K 8644显著预防了麻醉剂引起的幅度降低（P < 0.05）。我们得出结论，七氟烷、异氟烷和氟烷对培养的新生大鼠心室肌细胞具有直接心肌抑制作用，并且肌膜L型钙通道电流水平的降低介导了在这些未成熟心脏中观察到的心肌抑制。
七氟烷、异氟烷和氟烷对未成熟心脏的心脏兴奋 - 收缩偶联具有直接的心脏抑制作用，这是由与L型钙通道的相互作用介导的。
