Mechanisms of desflurane-induced preconditioning in isolated human right atria in vitro

Background: The authors examined the role of adenosine triphosphate-sensitive potassium (K-ATP) channels, adenosine A(1) receptor, and alpha and beta adrenoceptors in desflurane-induced preconditioning in human myocardium, in vitro. Methods: The authors recorded isometric contraction of human right atrial trabeculae suspended in oxygenated Tyrode's solution (34degreesC; stimulation frequency, 1 Hz). Before a 30-min anoxic period, 3, 6, and 9% desflurane was administered during 15 min. Desflurane, 6%, was also administered in the presence of 10 muM glibenclamide, a K-ATP channels antagonist; 10 muM HMR 1098, a sarcolemmal K-ATP channel antagonist; 800 muM 5-hydroxy-decanoate (5-HD), a mitochondrial K-ATP channel antagonist, 1 muM phentolamine, an alpha-adrenoceptor antagonist; 1 muM propranolol, a beta-adrenoceptor antagonist; and 100 nm 8-cyclopentyl-1,3-dipropylxanthine (DPX), the adenosine A, receptor antagonist. Developed force at the end of a 60-min reoxygenation period was compared (mean +/- SD). Results: Desflurane at 3% (95 +/- 13% of baseline), 6% (86 +/- 6% of baseline), and 9% (82 +/- 6% of baseline) enhanced the recovery of force after 60 min of reoxygenation as compared with the control group (50 +/- 11% of baseline). Glibenclamide (60 +/- 12% of baseline), 5-HD (57 +/- 21% of baseline), DPX (63 +/- 19% of baseline), phentolamine (56 +/- 20% of baseline), and propranolol (63 +/- 13% of baseline) abolished desflurane-induced preconditioning. In contrast, HMR 1098 (85 +/- 12% of baseline) did not modify desflurane-induced preconditioning. Conclusions: In vitro, desflurane preconditions human myocardium. against simulated ischemia through activation of mitochondriaI K-ATP channels, adenosine A(1) receptor, and alpha and beta adrenoceptors.