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 α and β 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 (34°C; 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 μM glibenclamide, a K ATP channels antagonist; 10 μM HMR 1098, a sarcolemmal K ATP channel antagonist; 800 μM 5-hydroxy-decanoate (5-HD), a mitochondrial K ATP channel antagonist; 1 μM phentolamine, an α-adrenoceptor antagonist; 1 μM propranolol, a β-adrenoceptor antagonist; and 100 nM 8-cyclopentyl-1,3-dipropylxanthine (DPX), the adenosine A 1 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 mitochondrial K ATP channels, adenosine A 1 receptor, and α and β adrenoceptors.