The effects of inhalational anesthetic agents on myocardial contraction have been the focus of extensive investigations for many years, and the depression of force development by different inhalational agents has been repeatedly shown. Ding et al. investigated whether decreasing myofilament Ca2+ responsiveness is central to isoflurane (ISO)-induced reduction in cardiac force development and also whether depression of cardiac force could be reversed by a nitroxyl (HNO) donor. It was demonstrated, with the use of isolated myofibrils, that ISO depressed force in a dose-dependent manner without significantly altering internal calcium levels. This demonstrated that ISO depresses cardiac force development by decreasing myofilament Ca2+ responsiveness and that myofilament Ca2+ sensitization by the HNO donor 1-nitrosocyclohexyl acetate (NCA) can effectively restore force development without additional increases in internal calcium levels. HNO donors are therefore likely to be able to provide an inotropic counterbalancing effect in patients displaying compromised cardiac function. These studies indicate that cardiac depression during anesthesia, especially in patients with heart failure, is more effectively and efficiently treated with positive inotropic agents that possess Ca2+-sensitizing properties similar to those of the HNO donor NCA.
See article at J Pharmacol Exp Ther 2011, 339:825–831.
- Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics