Adenosine A(1)-receptor induced late preconditioning and myocardial infarction: reperfusion duration is critical.
We investigated the influence of coronary artery reperfusion (CAR) duration on the infarct-limiting properties of adenosine A(1)-receptor stimulation-induced delayed preconditioning (A(1)-DPC) compared with 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, iv), I-DPC (six 4-min coronary artery occlusion/4-min reperfusion cycles), A(1)-DPC(100) (N(6)-cyclopentyladenosine, 100 microg/kg iv), and A(1)-DPC(400) (N(6)-cyclopentyladenosine, 400 microg/kg iv). 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 3 or 72 h. Infarct size (percentage of the area at risk) was determined by triphenyltetrazolium chloride staining. After 3 h of CAR, I-DPC, A(1)-DPC(100), and A(1)-DPC(400) significantly decreased infarct size (36 +/- 5, 41 +/- 4, 38 +/- 5%, respectively) compared with control (55 +/- 3%). After 72 h of CAR, infarct sizes were not significantly different among the four groups. This result was confirmed by histologic analysis. Thus A(1)-DPC at the two investigated doses, as well as I-DPC, decreased infarct size after 3 h but not 72 h of CAR.
Tissier
Renaud
R
Département de Pharmacologie, Faculté de Médecine Paris Sud and Institut National de la Santé et de la Recherche Médicale E00.01, 94276 Le Kremlin-Bicêtre Cedex, France.
Souktani
Rachid
R
Bruneval
Patrick
P
Giudicelli
Jean-François
JF
Berdeaux
Alain
A
Ghaleh
Bijan
B
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D006328:Cardiac Catheterization; D003331:Coronary Vessels / Q000503:physiopathology; D004195:Disease Models, Animal; D018450:Disease Progression; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control; D015425:Myocardial Reperfusion / Q000379:methods*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D058906:Purinergic P1 Receptor Agonists; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome; D014851:Wakefulness
D058906:Purinergic P1 Receptor Agonists; D018047:Receptors, Purinergic P1; C048599:N(6)-cyclopentyladenosine; D000241:Adenosine