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Am J Physiol Heart Circ Physiol (February 14, 2002). doi:10.1152/ajpheart.00866.2001
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Articles in PresS, published online ahead of print February 14, 2002
Am J Physiol Heart Circ Physiol, 10.1152/ajpheart.00866.2001
Submitted on October 5, 2001
Accepted on February 11, 2002

Adenosine A1-receptor induced late preconditioning and myocardial infarction: reperfusion duration is critical

Renaud Tissier1, Rachid SIouktani1, Patrick Bruneval2, Jean-Francois Giudicelli1, Alain Berdeaux1*, and Bijan Ghaleh1

1 Departement de Pharmacologie, INSERM E 00.01, Faculte de Medecine Paris-Sud, Le Kremlin-Bicetre, France
2 INSERM U 430, Hopital Broussais, Paris, France

* To whom correspondence should be addressed. E-mail: alain.berdeaux{at}kb.u-psud.fr.

We investigated the influence of coronary artery reperfusion duration (CAR) on the infarct-limiting properties of adenosine A1-receptor stimulation-induced delayed preconditioning (A1-DPC) as compared to ischemia-induced delayed preconditioning (I-DPC). Sixty-one chronically instrumented conscious rabbits successfully underwent the following protocol. On day 1, rabbits were randomly divided into four groups: Control (saline, i.v.), I-DPC (six 4-min coronary artery occlusion / 4-min reperfusion cycles), A1-DPC100 (N6-cyclopentyladenosine, 100 µg/kg, i.v.), and A1-DPC400 (N6-cyclopentyladenosine, 400 µg/kg, i.v.). On day 2 (i.e., 24 h later), rabbits underwent a 30-min coronary artery occlusion after which CAR was started and maintained for either 3h or 72h. Infarct size (% of the area at risk) was determined by triphenyltetrazolium chloride (TTC) staining. After 3h-CAR, I-DPC, A1-DPC100 and A1-DPC400 significantly decreased infarct size (36±5, 41±4, 38±5%, respectively) as compared to Control (55±3%). After 72h-CAR, infarct sizes were not significantly different among the four groups. This result was confirmed by histological analysis. Thus, A1-DPC at the two investigated doses, as well as I-DPC, decreased infarct size after 3h- but not 72h-CAR.




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