Beta1-adrenoreceptor Activation Contributes to Ischemia-reperfusion Damage As Well As Playing a Role in Ischemic Preconditioning.
From: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, 3800 Spruce Street, Philadelphia PA 19104-6046, USA. spearj@vet.upenn.edu
American journal of physiology. Heart and circulatory physiology
- Publish Date: May 2007
- ISSN: 0363-6135
- Volume: 292
- Issue: 5
- Pages: H2459-66
- Medium: Print
- Language: English
- Citation (JAMA): Spear Joseph F, Prabu Subbuswamy K, Galati Domenico, et al. Beta1-adrenoreceptor Activation Contributes to Ischemia-reperfusion Damage As Well As Playing a Role in Ischemic Preconditioning.. Am. J. Physiol. Heart Circ. Physiol. May 2007;292:H2459-66
Abstract
Protein kinase A (PKA) activation has been implicated in early-phase ischemic preconditioning. We recently found that during ischemia PKA activation causes inactivation of cytochrome-c oxidase (CcO) and contributes to myocardial damage due to ischemia-reperfusion. It may be that beta-adrenergic stimulation during ischemia via endogenous catecholamine release activates PKA. Thus beta-adrenergic stimulation may mediate both myocardial protection and damage during ischemia. The present studies were designed to determine the role of the beta(1)-adrenergic receptor (beta(1)-AR) in myocardial ischemic damage and ischemic preconditioning. Langendorff-perfused rabbit hearts underwent 30-min ischemia by anterior coronary artery ligation followed by 2-h reperfusion. Occlusion-reperfusion damage was evaluated by delineating the nonperfused volume of myocardium at risk and volume of myocardial necrosis after 2-h reperfusion. In some hearts ischemic preconditioning was accomplished by two 5-min episodes of global low-flow ischemia separated by 10 min before coronary occlusion-reperfusion. Orthogonal electrocardiograms were recorded, and coronary flow was monitored by a drip count. Three hearts from each experimental group were used to determine mitochondrial CcO and aconitase activities. Two-hour reperfusion after occlusion caused an additional decrease in CcO activity vs. that after 30-min occlusion alone. Blocking the beta(1)-AR during occlusion-reperfusion reversed CcO activity depression and preserved myocardium at risk for necrosis. Similarly, mitochondrial aconitase activity exhibited a parallel response after occlusion-reperfusion as well as for the other interventions. Furthermore, classic ischemic preconditioning had no effect on CcO depression. However, blocking the beta(1)-AR during preconditioning eliminated the cardioprotection. If the beta(1)-AR was blocked after preconditioning, the myocardium was preserved. Interestingly, in both of the latter cases the depression in CcO activity was reversed. Thus the beta(1)-AR plays a dual role in myocardial ischemic damage. Our findings may lead to therapeutic strategies for preserving myocardium at risk for infarction, especially in coronary reperfusion intervention.
Mesh Headings (Keywords): Animals, Ischemic Preconditioning, Myocardial, Male, Myocardial Reperfusion Injury, Rabbits, Receptors, Adrenergic, beta-1
Check for Full Text / PubMed Unique Identifier (PMID): 17237252
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