MYOCARDIAL DEPRESSANT EFFECTS OF SEVOFLURANE - MECHANICAL AND ELECTROPHYSIOLOGIC ACTIONS IN-VITRO

Background: The effects of anesthetic concentrations of sevoflurane we re studied in isolated myocardial tissue to delineate the mechanisms b y which cardiac function is altered. Methods: Isometric force of isola ted guinea pig ventricular papillary muscle was studied at 37 degrees C in normal and 26 mM K+ Tyrode's solution at various stimulation rate s. Normal and slow action potentials were evaluated using conventional microelectrodes. Effects of sevoflurane on sarcoplasmic reticulum fun ction in situ were also evaluated by its effect on rapid cooling contr actures, which are known to activate Ca2+ release from the sarcoplasmi c reticulum, and on contractions of rat papillary muscle, Finally, Ca2 + and K+ currents of isolated guinea pig ventricular myocytes were exa mined using the whole-cell patch clamp technique. Results: Sevoflurane equivalent to 1.4% and 2.8% depressed guinea pig myocardial contracti ons to similar to 85 and similar to 65% of control, respectively, alth ough the maximum rate of force development at 2 or 3 Hz and force in r at myocardium after rest showed less depression. In the partially depo larized, beta-adrenergically stimulated myocardium, sevoflurane select ively depressed late peak force without changing early peak force, whe reas it virtually abolished rapid cooling contractures. Sevoflurane di d not alter the peak amplitude or maximum depolarization rate of norma l and slow action potentials, but action potential duration was signif icantly prolonged. In isolated guinea pig myocytes at room temperature , 0.7 mM sevoflurane (equivalent to 3.4%) depressed peak Ca2+ current by similar to 25% and increased the apparent rate of inactivation. The delayed outward K+ current was markedly depressed, but the inwardly r ectifying K+ current was only slightly affected by 0.35 mM sevoflurane . Conclusions: These results suggest that the direct myocardial depres sant effects of sevoflurane are similar to those previously described for isoflurane. The rapid initial release of Ca2+ from the sarcoplasmi c reticulum is not markedly decreased, although certain release pathwa ys, specifically those induced by rapid cooling, appear to be depresse d. Contractile depression may be partly related to the depression of C a2+ influx through the cardiac membrane. The major electrophysiologic effect of sevoflurane seems to be a depression of the delayed outward K+ current, which appears to underlie the increased action potential d uration.