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Adenosine type 1 (A1) receptors mediate protection against myocardial infarction produced by chronic, intermittent ingestion of ethanol in dogs. Int J Cardiol 2003 Apr;88(2-3):175-82

Date

04/26/2003

Pubmed ID

12714196

DOI

10.1016/s0167-5273(02)00329-7

Abstract

BACKGROUND: Chronic consumption of small amounts of ethanol protects myocardium from ischemic injury. We tested the hypothesis that adenosine type 1 (A(1)) receptors mediate these beneficial effects.

METHODS: Dogs (n=37) were fed with ethanol (1.5 g/kg) or water mixed with dry food twice per day for 12 weeks, fasted overnight before experimentation, and instrumented for measurement of hemodynamics. Dogs received intravenous drug vehicle (50% polyethylene glycol in 0.1 N sodium hydroxide and 0.9% saline over 15 min) or the selective A(1) receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 0.8 mg/kg over 15 min) and were subjected to a 60 min coronary artery occlusion followed by 3 h of reperfusion. Myocardial infarct size and transmural coronary collateral blood flow were measured with triphenyltetrazolium chloride staining and radioactive microspheres, respectively.

RESULTS: The area at risk (AAR) for infarction was similar between groups. Pretreatment with ethanol significantly reduced infarct size to 13+/-2% (n=7) of the AAR as compared to control experiments (26+/-2%; n=7). DPCPX abolished the protective effects of ethanol pretreatment (30+/-3%; n=7) but had no effect in dogs that did not receive ethanol (25+/-2%; n=7). No differences in transmural coronary collateral blood flow were observed between groups.

CONCLUSIONS: The present findings indicate that chronic ingestion of small amounts of ethanol produces myocardial protection that persists after the discontinuation of ethanol. The results indicate that A(1) receptors mediate ethanol-induced preconditioning in dogs independent of alterations in systemic hemodynamics or coronary collateral blood flow.

Author List

Kehl F, Krolikowski JG, LaDisa JF Jr, Kersten JR, Warltier DC, Pagel PS

Authors

John LaDisa PhD Assistant Professor in the Biomedical Engineering department at Marquette University
Paul S. Pagel MD, PhD Professor in the Anesthesiology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Administration, Oral
Animals
Collateral Circulation
Coronary Circulation
Disease Models, Animal
Dogs
Dose-Response Relationship, Drug
Drug Administration Schedule
Ethanol
Hemodynamics
Ischemic Preconditioning, Myocardial
Myocardial Infarction
Receptors, Purinergic P1
Severity of Illness Index
Solvents
Xanthines
jenkins-FCD Prod-387 b0ced2662056320369de4e5cd5f21c218c03feb3