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

Jee, Young Seok; Lee, Kee Young; Kim, Myung Hee; Lee, Won Jae; Park, Wyun Kon

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 K+ 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 Na+ Tyrode's solution (25 mM) were performed to evaluate the effect of Ca2+ 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, Ca2+ 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 Na+ 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 Ca2+ 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 Ca2+ currents through the cardiac membrane. Therefore, it is likely that various methods employed to enhance inward Ca2+ current may improve the hemodynamic depression induced by desflurane.