Isoflurane, but not halothane, induces protection of human myocardium via adenosine A(1) receptors and adenosine triphosphate-sensitive potassium channels

Background: Volatile anesthetics produce differing degrees of myocardial pr otection in animal models of ischemia. The purpose of the current investiga tion was to determine the influence of isoflurane and halothane on myocardi al protection in a human model of simulated ischemia and the role of adenos ine A(1) receptors and adenosine triphosphate-sensitive potassium (K-ATP) c hannels in the anesthetic pathway, Methods: Human atrial trabecular muscles were superfused with oxygenated Kr ebs-Henseleit buffer and stimulated at 1 Hz, with recording of maximum cont ractile force. Fifteen minutes before a 30-min anoxic insult, muscles were pretreated for 5 min with either anoxia, the A1 agonist N-6-cyclohexyladeno sine, 1% halothane or 1.2% isoflurane. These treatments were also performed in the presence of either the K-ATP channel antagonist glibenclamide or th e A, receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX). Anesth etic 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-pre treated 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 w ith DPCPX. Halothane treatment provided no cardioprotection and seemed to i nhibit 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 isoflu rane in contrast to the effects of halothane. Furthermore, A1 receptors and K-ATP channels seem to mediate the beneficial effects of anoxia and isoflu rane in human myocardium.