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

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 pl atelet cyclooxygenase-dependent formation of thromboxane A(2) (TxA(2)) has been proposed for sevoflurane. Therefore, we analyzed the influence of sevo flurane on cardiac performance and TxA(2) production after intracoronary ap plication of platelets in isolated guinea pig hearts. Isolated guinea pig hearts perfused with Krebs-Henseleit buffer and perform ing pressure-volume work were employed. We compromised myocardial function by subjecting hearts to ischemia (20 ruin low-flow plus 10 min stopped-flow ) and reperfusion. During low-flow perfusion the coronary endothelium was s timulated by thrombin prior to and during infusion of a bolus of 10(8) wash ed human platelets. Intervention groups contained either sevoflurane in a c oncentration being equivalent to 1 PI IAC in the platelet suspension or in the perfusate or 1 mu M SQ29,548 (an isoprostane- and thromboxane-receptor antagonist) in the perfusate. The parameter external heart work (EHW), dete rmined pre- and postischemically, served as criterion for loss of myocardia l function. Additionally, formation of transudate and the production of TxA (2) 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 re perfusion, but strongly attenuated coronary vascular leak, Sevoflurane redu ced platelet adhesion when applied to the perfusate, but not when given onl y to the platelet suspension. However, platelets pretreated with sevofluran e lost their cardiodepressive effects, as did platelets in hearts treated w ith SQ29,548. Surprisingly, TxA(2) formation in hearts was not different af ter platelet application in comparison to the ischemia control group, but w as significantly reduced when sevoflurane was applied to the perfusate. Nei ther metabolic parameters, coronary perfusion pressure, vascular leak nor g lycoprotein expression of platelets were influenced by sevoflurane. Conclusions: 1) Pretreatment of hearts with sevoflurane reduces intracorona ry platelet adhesion, most likely via an endothelial mechanism. 2) Pretreat ment of platelets with sevoflurane doss not reduce platelet adhesion, but n evertheless averts cardiodepressive effects derived from or generated by ad herent platelets. 3) Transudate formation of hearts during reperfusion was reduced after platelet application, independent of the adherence of platele ts.