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

吸入麻醉药因其麻醉深度稳定，无严重并发症而被广泛应用。然而，心血管系统的抑制并不罕见。这种抑郁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，很难排除血管、神经原性和激素效应的影响。用培养的心肌细胞进行实验，可以消除在体实验中所见的效应，从而可以在相对独立的条件下明确麻醉药的直接心脏抑制作用。1）磷酸二酯酶抑制剂的作用（氨力农），Ca^2+敏化（2）KATP通道开放剂对氟烷心肌抑制作用的影响（cromakalim），阻滞剂（格列本脲）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+>通道激动剂的作用（Bay K 8644）对各种吸入麻醉剂在培养的大鼠心肌细胞中的心肌抑制作用的影响。一些吸入麻醉剂以浓度依赖性方式显示心脏抑制作用，并且这些作用在氟烷>异氟烷>七氟烷中突出。这些心肌抑制作用可能与抑制L-型Ca^<2+>通道有关。氟烷的心肌抑制作用与降低细胞内cAMP浓度、降低收缩蛋白对Ca^2+的敏感性及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.