Protection From AMP 579 Can Be Added to That From Either Cariporide or Ischemic Preconditioning in Ischemic Rabbit Heart

Abstract

AMP 579, an adenosine A /A receptor agonist, is cardioprotective when administered at reperfusion. Pretreatment with the Na /H exchanger inhibitor cariporide or ischemic preconditioning (PC) also limits infarct size. To gain insight into the mechanism of AMP 579 we investigated whether its protection could be added to that from either cariporide or PC. rabbit hearts were subjected to 45 min of regional ischemia followed by 3 h of reperfusion. Infarct size in the control group was 55.8 +/- 3.9% of the risk zone. PC significantly reduced infarct size to 26.0 +/- 6.7% (p<0.05). AMP 579 (30 micro g/kg) given just before reperfusion followed by 3 micro g/kg/min infusion for 70 min also limited infarct size (32.1 +/- 1.8%,) but the combination of AMP 579 and PC showed a significantly greater limitation of infarct size (5.5 +/- 2.7%, p < 0.05). Because cariporide pretreatment was so protective (8.5 +/- 3.7% infarction), we had to increase the ischemic insult to 60 min to test for any additive effect of the combination of AMP 579 + cariporide. Infarct size in the untreated group was 66.0 +/- 4.9% of the risk zone. Cariporide (0.5 mg/kg) 5 min prior to ischemia significantly reduced infarct size to 41.5 +/- 7.7%. When cariporide pre-treatment was combined with AMP 579 at reperfusion, infarction was further limited (14.2 +/- 4.5%). Because AMP 579's protection can be added to that of either cariporide or PC, AMP 579's mechanism of protection probably differs from either of them. The combination of AMP 579 + cariporide was particularly efficacious and could be useful in the surgical setting.

Adenosine produces nitric oxide and prevents mitochondrial oxidant damage in rat cardiomyocytes

“…In addition, Zhao et al reported that adenosine at reperfusion can block ischemia-reperfusion-induced apoptosis by activating A 2 receptors [36]. Recently, Xu et al have demonstrated that AMP579, a novel adenosine A 1 /A 2 receptor agonist, given at reperfusion significantly reduces infarct size in rabbit hearts [37,38], and that the activation of adenosine A 2 receptors at reperfusion accounts for the protective effects of AMP579 [37]. Interestingly, Yang et al have documented that the NECA-induced cardioprotection against infarction at reperfusion was blocked by both the adenosine A 2 receptor antagonist CSC and the NOS inhibitor l-NAME [5].…”

Preconditioning in Intact and Previously Diseased Myocardium: Laboratory or Clinical Dilemma?

“…One to four cycles of ischemic PC were selected for our studies in the isolated working rabbit heart, because generally one to four PC cycles protected the ischemic myocardium, in various degree, against the incidence of reperfusion-induced damage in the models of PC in intact myocardium (10,20,26,29,41,42,55,57,58,72). PC studies have been carried out after 8 weeks of cholesterol diet, and comparisons were made with the age-matched noncholesterolemic groups.…”

The p38 MAPK Inhibitor SB203580 Blocks Adenosine A1 Receptor-Induced Attenuation of In Vivo Myocardial Stunning

“…On the other hand, AMP579 is a unique agent with high affinity for both adenosine A 1 and A 2A receptors, and it has been shown to exert much less hemodynamic effects in vivo [10,[26][27][28][29]. Treatment with AMP579, both prior to ischemia and during reperfusion, reduces in vivo infarct size in several species [26][27][28][29][30][31], due to its ability to activate both adenosine A 1 and A 2A receptors.…”

“…Treatment with AMP579, both prior to ischemia and during reperfusion, reduces in vivo infarct size in several species [26][27][28][29][30][31], due to its ability to activate both adenosine A 1 and A 2A receptors. We have recently reported that pretreatment with AMP579 dose-dependently attenuated in vivo myocardial stunning, with only minor, transient reductions in HR and MAP [10].…”