The volatile anesthetic sevoflurane mitigates cardiodepressive effects of platelets in reperfused hearts.

Abstract

Adherent platelets in the coronary system can impair cardiac pump function. The volatile anesthetics sevoflurane, halothane, and isoflurane have been shown to reduce platelet adhesion. Additionally, an inhibitory effect on platelet cyclo-oxygenase-dependent formation of thromboxane A2 (TxA2) has been proposed for sevoflurane. Therefore, we analyzed the influence of sevoflurane on cardiac performance and TxA2 production after intracoronary application of platelets in isolated guinea pig hearts. Isolated guinea pig hearts perfused with Krebs-Henseleit buffer and performing pressure-volume work were employed. We compromised myocardial function by subjecting hearts to ischemia (20 min low-flow plus 10 min stopped-flow) and reperfusion. During low-flow perfusion the coronary endothelium was stimulated by thrombin prior to and during infusion of a bolus of 10(8) washed human platelets. Intervention groups contained either sevoflurane in a concentration being equivalent to 1 MAC in the platelet suspension or in the perfusate or 1 microM SQ29,548 (an isoprostane- and thromboxane-receptor antagonist) in the perfusate. The parameter external heart work (EHW), determined pre- and postischemically, served as criterion for loss of myocardial function. Additionally, formation of transudate and the production of TxA2 were measured during the reperfusion phase. Coronary perfusion pressure and myocardial production of lactate and consumption of pyruvate were also determined. Adherent platelets significantly enhanced loss of EHW after ischemia and reperfusion, but strongly attenuated coronary vascular leak. Sevoflurane reduced platelet adhesion when applied to the perfusate, but not when given only to the platelet suspension. However, platelets pretreated with sevoflurane lost their cardiodepressive effects, as did platelets in hearts treated with SQ29,548. Surprisingly, TxA2 formation in hearts was not different after platelet application in comparison to the ischemia control group but was significantly reduced when sevoflurane was applied to the perfusate. Neither metabolic parameters, coronary perfusion pressure, vascular leak nor glycoprotein expression of platelets were influenced by sevoflurane. 1) Pretreatment of hearts with sevoflurane reduces intracoronary platelet adhesion, most likely via an endothelial mechanism. 2) Pretreatment of platelets with sevoflurane does not reduce platelet adhesion, but nevertheless averts cardiodepressive effects derived from or generated by adherent platelets. 3) Transudate formation of hearts during reperfusion was reduced after platelet application, independent of the adherence of platelets.