Dilazep dihydrochloride prolongs the infarct size-limiting effect of ischemic preconditioning in rabbits.
Recent studies have indicated the key role of adenosine receptor activation as a trigger for ischemic preconditioning (PC). Hence, the augmentation of endogenous adenosine may potentiate the cardioprotective effects of PC. In this study. we aimed to test the hypothesis that dilazep dihydrochloride, an adenosine transport inhibitor, potentiates the PC effect. Protocol 1: Infarcts were produced in open-chest anesthetized rabbits by 30-min occlusion of a coronary artery and 2 days' reperfusion. PC was elicited by a preceding 5-min occlusion and either 5, 40, or 120 min of reperfusion. PC with the 5-min reperfusion markedly limited the infarct size after the 30-min ischemia (infarct size to area at risk (IS): 10%+/-3% vs 41%+/-3%, P < 0.05). PC was not protective when the reperfusion periods were 40 or 120 min (IS: 47%+/-5% and 44%+/-3%. P = not significant (NS) vs control, respectively). However, concomitant treatment with dilazep (0.2mg/kg) preserved the PC effect in the 40-min reperfusion group (18%+/-5%, P < 0.05 vs control) but not in the 120-min reperfusion group (43%+/-4%, P = NS vs control). Protocol 2: Infarct was produced in a similar rabbit model by either a 45- or 50-min occlusion of a coronary artery and 2 days of reperfusion. PC was elicited by a preceding 5-min occlusion and a 5-min reperfusion. PC was protective in the 45-min occlusion group (30%+/-7% vs 67%+/-3%, P < 0.05) but not in the 50-min occlusion group (74%+/-4% vs 79%+/-5%, P = NS). Treatment with dilazep (0.2mg/kg) failed to retrieve protection in this preconditioned group (77%+/-6%, P = NS vs 50-min occlusion group without PC). Thus, dilazep prolonged the infarct size-limiting effect of PC, but failed to retrieve protection in the group with a longer sustained ischemia.
Yamasaki
K
K
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Japan.
Tanaka
M
M
Yokota
R
R
Fujiwara
H
H
Sasayama
S
S
D000818:Animals; D004109:Dilazep / Q000378:metabolism / Q000494:pharmacology*; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology*; D058915:Purinergic P1 Receptor Antagonists; D011817:Rabbits; D018047:Receptors, Purinergic P1 / Q000378:metabolism; D014665:Vasodilator Agents / Q000378:metabolism / Q000494:pharmacology*
D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014665:Vasodilator Agents; D004109:Dilazep