Gene transfer of β2 adrenergic receptor enhances cardioprotective effects of ischemic preconditioning in rat hearts after myocardial infarction

Abstract

Objective: The purpose of the present study was to determine a role of β2 adrenergic receptor (β2AR) in ischemic preconditioning (IPC) response. Methods: Post-myocardial infarction (MI) hearts were produced by ligating the left anterior descending coronary artery for 2 weeks. Post-MI hearts were transfected with the empty virus (Empty-vivo) or β2AR cDNA (β2AR-vivo) by intracoronary infusion of hemagglutinating virus of Japan-liposome. Empty-vivo or β2AR- vivo hearts were subjected to Langendorff perfusion as Control or β2AR hearts, respectively. IPC was undertaken in Control(IPC) and β2AR(IPC+β2AR). After global ischemia, seven hearts in each group were reperfused and normalized left ventricular peak developed pressures (LVPDP) and creatine phosphokinase (CPK) leakage were measured. β2AR gene transfection was confirmed by measuring responsiveness to isoproterenol, real time RT-PCR and immunohistochemistory. Results: IPC preserved LVPDP and reduced CPK leakage in IPC+β2AR hearts as compared with IPC hearts. LVPDP was decreased in addition to increase in CPK leakage in β2AR hearts as compared with Control. Expression of β2AR and responsiveness to isoproterenol were increased in β2AR-vivo as compared with Empty-vivo hearts. Conclusion: These results indicate that β2AR are required to generate IPC effects, and that β2AR gene transfection enhances IPC effects in post-MI hearts. © 2005 Published by European Association for Cardio-Thoracic Surgery. All rights reserved.