Journal
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
Volume 41, Issue 3, Pages 396-405Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00005344-200303000-00008
Keywords
beta-adrenoceptor; atenolol; ICI 118,551; isoproterenol; perfused rat heart; preconditioning
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Using an isolated nonworking rat heart model, this study investigated the role of beta-adrenergic preconditioning (beta-PC) to attenuate myocardial dysfunction after an ischemia/reperfusion injury. After a 20-min stabilization period, the noradrenaline depleted hearts were perfused for 5 min with isoproterenol (ISO) before 40-min global ischemia (I) followed by 30-min reperfusion (R). ISO 0.02 muM provided significant protection versus unconditioned in vivo reserpinized IR control, causing a decrease of creatine kinase (CK) release (mIU/min/g wet weight) on reperfusion in coronary effluent, a preservation of the mean coronary flow (MCF) and preservation of left ventricular function assessed by the rate-pressure product (RPP). These beneficial effects were similar to those of ischemic preconditioning (I-PC) in both nonreserpinized and reserpinized rats. Propranolol (1 muM) and atenolol (10 muM) completely suppressed the ISO preconditioning. In contrast, ICI 118,551 (2 muM), a highly selective beta(2)-blocker, did not blunt the salutary effects of ISO on CK release and MCF preservation. These results indicate that ISO pretreatment provides a significant cardioprotection against prolonged ischemic myocardial injury. Although endogenous catecholamines are not necessary for I-PC in isolated rat hearts, cardioprotection provided by beta-adrenergic stimulation is quite similar to I-PC. This significant cardioprotection is mediated less by beta(2)-adrenoceptor than by beta(1)-adrenoceptor activation, which seems to play a crucial role in the beta-PC mechanism.
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