Mechanisms of sevoflurane-induced myocardial preconditioning in isolated human right atria in vitro

Abstract

Background: The authors examined the role of adenosine triphosphate - sensitive potassium channels and adenosine A1 receptors in sevoflurane-induced preconditioning on isolated human myocardium. Methods: The authors recorded isometric contraction of human right atrial trabeculae suspended in oxygenated Tyrode's solution (34°C; stimulation frequency, 1 Hz). In all groups, a 30-min hypoxic period was followed by 60 min of reoxygenation. Seven minutes before hypoxia reoxygenation, muscles were exposed to 4 min of hypoxia and 7 min of reoxygenation or 15 min of sevoflurane at concentrations of 1, 2, and 3%. In separate groups, sevoflurane 2% was administered in the presence of 10 μM HMR 1098, a sarcolemmal adenosine triphosphate-sensitive potassium channel antagonist; 800 μM 5-hydroxy-decanoate, a mitochondrial adenosine triphosphate-sensitive potassium channel antagonist; and 100 nM 8-cyclopentyl-1,3-dipropylxanthine, an adenosine A1 receptor antagonist. Recovery of force at the end of the 60-min reoxygenation period was compared between groups (mean ± SD). Results: Hypoxic preconditioning (90 ± 4% of baseline) and sevoflurane 1% (82 ± 3% of baseline), 2% (92 ± 5% of baseline), and 3% (85 ± 7% of baseline) enhanced the recovery of force after 60 min of reoxygenation compared with the control groups (52 ± 9% of baseline). This effect was abolished in the presence of 5-hydroxy-decanoate (55 ± 14% of baseline) and 8-cyclopentyl-1,3-dipropylxanthine (58 ± 16% of baseline) but was attenuated in the presence of HMR 1098 (73 ± 10% of baseline). Conclusions: In vitro, sevoflurane preconditions human myocardium against hypoxia through activation of adenosine triphosphate-sensitive potassium channels and stimulation of adenosine A1 receptors.