Hannon James D, Cody Mark J, Sun David X, Housmans Philippe R
Department of Anesthesiology, Mayo Foundation, Rochester, Minnesota 55905, USA.
Anesthesiology. 2004 Sep;101(3):675-86. doi: 10.1097/00000542-200409000-00016.
Depression of myocardial contractility as a result of isoflurane appears to be greater in myocardial hypertrophy, and the cellular basis for this difference in susceptibility is not clear. In this study we examined the effects of isoflurane and sevoflurane on contractility and intracellular calcium in an animal model of pressure-overload hypertrophy.
Pressure-overload hypertrophy was established in young male ferrets by banding the main pulmonary artery for 1 month and the effects of isoflurane and sevoflurane on contractility and intracellular calcium ([Ca]i) were examined in isolated right ventricular papillary muscles, trabeculae, and myocytes. Intracellular calcium was measured with the bioluminescent photoprotein aequorin in isolated papillary muscles, and also with the fluorescent indicator fluo-3 in isolated ventricular myocytes. In addition, Ca sensitivity was assessed in isolated trabeculae after disruption of the surface membrane with a nonionic detergent (skinned fibers).
In the presence of isoflurane and sevoflurane, papillary muscles from banded animals exhibited a greater depression of contractility and isolated ventricular myocytes showed a greater decrease in peak [Ca]i. Furthermore, baseline calcium sensitivity was decreased and the slope of the relationship between [Ca] and force was increased in skinned trabeculae from banded animals. Isoflurane decreased calcium sensitivity in trabeculae from both normal and banded animals.
These results suggest that changes in [Ca]i and altered calcium sensitivity are both responsible for the exaggerated effects of some volatile anesthetics on contractility in pressure-overload hypertrophy.
异氟烷导致的心肌收缩力抑制在心肌肥厚时似乎更明显，而这种易感性差异的细胞基础尚不清楚。在本研究中，我们在压力超负荷肥大的动物模型中研究了异氟烷和七氟烷对收缩力和细胞内钙的影响。
通过结扎年轻雄性雪貂的主肺动脉1个月建立压力超负荷肥大模型，并在分离的右心室乳头肌、小梁和心肌细胞中研究异氟烷和七氟烷对收缩力和细胞内钙（[Ca]i）的影响。在分离的乳头肌中用生物发光光蛋白水母发光蛋白测量细胞内钙，在分离的心室肌细胞中用荧光指示剂fluo-3测量。此外，在用非离子去污剂破坏表面膜后（去皮纤维），在分离的小梁中评估钙敏感性。
在异氟烷和七氟烷存在的情况下，结扎动物的乳头肌收缩力抑制更明显，分离的心室肌细胞的[Ca]i峰值下降更大。此外，结扎动物的去皮小梁的基线钙敏感性降低，[Ca]与力之间关系的斜率增加。异氟烷降低了正常和结扎动物小梁的钙敏感性。
这些结果表明，[Ca]i的变化和钙敏感性的改变均导致某些挥发性麻醉剂对压力超负荷肥大时收缩力的夸大作用。
