Isoflurane, but not halothane, induces protection of human myocardium via adenosine A1 receptors and adenosine triphosphate-sensitive potassium channels

Abstract

Background: Volatile anesthetics produce differing degrees of myocardial protection in animal models of ischemia. The purpose of the current investigation was to determine the influence of isoflurane and halothane on myocardial protection in a human model of simulated ischemia and the role of adenosine A1 receptors and adenosine triphosphate-sensitive potassium (K(ATP)) channels in the anesthetic pathway. Methods: Human atrial trabecular muscles were superfused with oxygenated Krebs-Henseleit buffer and stimulated at 1 Hz, with recording of maximum contractile force. Fifteen minutes before a 30-min anoxic insult, muscles were pretreated for 5 min with either anoxia, the A1 agonist N6-cyclohexyladenosine, 1% halothane or 1.2% isoflurane. These treatments were also performed in the presence of either the K(ATP) channel antagonist glibenclamide or the A1 receptor antagonist 8- cyclopentyl-1,3-dipropylxanthine (DPCPX). Anesthetic effects were also determined on K(ATP) currents in isolated whole cell voltage-clamped human atrial myocytes. Results: Recovery of force (recorded 60 min after anoxia) in isoflurane-pretreated muscles was reduced from 76.6 ± 7.5% of baseline to 43.7 ± 7.1% by pretreatment with glibenclamide, and to 52.5 ± 6.2% by pretreatment with DPCPX. Halothane treatment provided no cardioprotection and seemed to inhibit protection by anoxic preconditioning. Halothane decreased whole cell K(ATP) currents in atrial myocytes, whereas isoflurane had no effects. Conclusions: This study demonstrates the cardioprotective effects of isoflurane in contrast to the effects of halothane. Furthermore, A1 receptors and K(ATP) channels seem to mediate the beneficial effects of anoxia and isoflurane in human myocardium.