Role of the β1-adrenergic pathway in anesthetic and ischemic preconditioning against myocardial infarction in the rabbit heart in vivo

Abstract

BACKGROUND: Anesthetic and ischemic preconditioning share similar signal transduction pathways. The authors tested the hypothesis that the β1-adrenergic signal transduction pathway mediates anesthetic and ischemic preconditioning in vivo. METHODS: Pentobarbital-anesthetized (30 mg/kg) rabbits (n = 96) were instrumented for measurement of systemic hemodynamics and subjected to 30 min of coronary artery occlusion and 3 h of reperfusion. Sixty minutes before occlusion, vehicle (control), 1.0 minimum alveolar concentration desflurane, or sevoflurane, and esmolol (30.0 mg·kg·h) were administered for 30 min, respectively. Administration of a single 5-min cycle of ischemic preconditioning was instituted 35 min before coronary artery occlusion. In separate groups, the selective blocker esmolol or the protein kinase A inhibitor H-89 (250 μg/kg) was given alone and in combination with desflurane, sevoflurane, and ischemic preconditioning. RESULTS: Baseline hemodynamics and area at risk were not significantly different between groups. Myocardial infarct size (triphenyltetrazolium staining) as a percentage of area at risk was 61 ± 4% in control. Desflurane, sevoflurane, and ischemic preconditioning reduced infarct size to 34 ± 2, 36 ± 5, and 23 ± 3%, respectively. Esmolol did not alter myocardial infarct size (65 ± 5%) but abolished the protective effects of desflurane and sevoflurane (57 ± 4 and 52 ± 4%, respectively) and attenuated ischemic preconditioning (40 ± 4%). H-89 did not alter infarct size (60 ± 4%) but abolished preconditioning by desflurane (57 ± 5%) and sevoflurane (61 ± 1%). Ischemic preconditioning (24 ± 7%) was not affected by H-89. CONCLUSIONS: The results demonstrate that anesthetic preconditioning is mediated by the β1-adrenergic pathway, whereas this pathway is not essential for ischemic preconditioning. These results indicate important differences in the mechanisms of anesthetic and ischemic preconditioning. Copyright © 2006, the American Society of Anesthesiologists, Inc. Lippincott Williams & Wilkins, Inc.