DIRECT MYOCARDIAL DEPRESSION EFFECTS OF INHALATIONAL ANESTHETICS IN CULTURED RAT CARDIAC MYOCYTES

吸入麻醉药被广泛使用，因为它们可以很容易地带来稳定的麻醉深度，没有任何严重的并发症。然而，心血管系统的抑制并不罕见。这种抑制的原因被认为是由吸入麻醉剂的心脏抑制作用引起的。在体内实验中，很难消除血管、神经源性和激素效应的影响。体外培养心肌细胞的实验可以消除在体内研究中看到的这些影响，因此可以在相对独立的条件下明确麻醉剂的直接心脏抑制作用。本研究的目的如下：1)磷酸二酯酶抑制剂（amrinone）、Ca^<2+>敏化剂（pimobendan）对氟烷心肌抑制作用的影响，2)KATP通道开启剂（cromakalim）、阻滞剂（glibenclamide）对氟烷心肌抑制作用的影响，3)氟烷对l型Ca^<2+>通道结合的影响，4)l型Ca^<2+>通道激动剂（Bay K 8644）对各种吸入麻醉药对培养大鼠心肌细胞心肌抑制作用的影响。结果表明，部分吸入性麻醉药具有浓度依赖性的心脏抑制作用，其中氟烷b>、异氟烷b>、七氟烷b>的抑制作用较明显。这些心肌抑制作用可能与l型Ca^<2+>通道的抑制有关。氟烷的心肌抑制作用与降低细胞内环AMP浓度、降低收缩蛋白对Ca^<2+>的敏感性、降低KATP通道无关。

Inhalational anesthetics are widely used because they can easily bring a stable depth of anesthesia without any serious complications. However suppression of cardiovascular system is not rare. The cause of this depression is believed to be delivered by the cardiac suppressive effect by inhalational anesthetics. It is difficult to delete the effects of the vascular, neurogenic, and hormonal effects in vivo experiments. Experiments using cultured cardiac myocytes cane eliminate those effects seen in vivo studies, and thefore it can make clear the direct cardiac suppressive effects of anesthetics in a relatively independent conditions.The purpose of this study are the followings ; 1) The effects of phosphodiesterase inhibitor (amrinone), Ca^<2+> sensitize (pimobendan) on the myocardial depression effect by halothane, 2) The effects of KATP channel opener (cromakalim), blocker (glibenclamide) on the myocardial depression effects of halothane, 3) The effect of halothane on L-type Ca^<2+> channel binding, 4) The effects of L-type Ca^<2+> channel agonist (Bay K 8644) on myocardial depression effect by various inhalational anesthetics in cultured rat cardiac myocytes.In results, some inhalational anesthetics showed cardiac depressive effects in a concentration-dependent manner, and those effects are prominent in halothane>isoflurane>sevoflurane. Those myocardial depression effects are supposed to have a relations with a suppression of L-type Ca^<2+> channel. Moreover, the myocardial depression effects of halothane is not related to lowering of intracellular cyclic AMP concentration, lowering of sensitivity to Ca^<2+> of contraction proteins, nor KATP channel.