Adenosine type 1 (A1) receptors mediate protection against myocardial infarction produced by chronic, intermittent ingestion of ethanol in dogs.
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.
Kehl
Franz
F
Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Krolikowski
John G
JG
LaDisa
John F
JF
Kersten
Judy R
JR
Warltier
David C
DC
Pagel
Paul S
PS
D000284:Administration, Oral; D000818:Animals; D003097:Collateral Circulation / Q000187:drug effects / Q000502:physiology; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D000431:Ethanol / Q000008:administration & dosage* / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D009203:Myocardial Infarction / Q000503:physiopathology* / Q000517:prevention & control*; D018047:Receptors, Purinergic P1 / Q000187:drug effects* / Q000502:physiology*; D012720:Severity of Illness Index; D012997:Solvents / Q000008:administration & dosage* / Q000627:therapeutic use*; D014970:Xanthines / Q000494:pharmacology
D018047:Receptors, Purinergic P1; D012997:Solvents; D014970:Xanthines; D000431:Ethanol; C051360:1,3-dipropyl-8-cyclopentylxanthine