Direct Myocardial Depressant Effect of Desflurane: Mechanical and Electrophysiological Actions in Vitro

Abstract

Background: Desflurane actions on myocardial contractility and cellular electrophysiologic behavior were studied in isolated guinea pig and rat right ventricular papillary muscles. Methods: The isometric force of isolated guinea pig ventricular papillary muscles was studied in normal and 26 mM Tyrode's solution at various stimulation rates. Experiments using rat papillary muscles under normal Tyrode's solution at the rested-state (RS) and using guinea pig papillary muscles under low Tyrode's solution (25 mM) were performed to evaluate the effect of release from the sarcoplasmic reticulum (SR). Effects of desflurane on SR function in situ were examined by its effect on rapid cooling contractures (RCCs). Normal and slow action potentials (APs) were evaluated by using a conventional microelectrode technique. Finally, currents of isolated guinea pig ventricular myocytes were examined using the whole cell patch clamp technique. Results: 1 MAC (minimum alveolar concentration: 6%) and 2 MAC desflurane were applied. 1 MAC and 2 MAC desflurane depressed guinea pig myocardial contractions by 30% and 60%, respectively, from RS to 3 Hz stimulation rates. 1 MAC (1.15%) and 2 MAC isoflurane depressed peak force by 25% and 45%, respectively. Contractile force after rest in rat and guinea pig myocardium under low Tyrode's solution showed modest depression. In the partially depolarized, adrenergically stimulated myocardium, 1 MAC and 2 MAC desflurane caused a marked depression of the late peak force (1 MAC:60%, 2 MAC:80%) with moderate changes of the early peak force (1 MAC: 20%, 2 MAC: 40%). RCCs were abolished at 1 MAC desflurane. Desflurane did not alter the peak amplitude or maximum depolarization rate of normal and slow APs, however, AP duration was significantly prolonged. In isolated guinea pig myocytes at room temperature, 1 MAC and 2 MAC desflurane caused a 28% and 55% decrease in currents, respectively. Conclusions: These results indicate that desflurane causes a dose-dependent depression of contractile force in isolated myocardium, which is comparable to that of isoflurane. The depression seems to be related, at least in part, to its ability to reduce inward currents through the cardiac membrane. Therefore, it is likely that various methods employed to enhance inward current may improve the hemodynamic depression induced by desflurane.