ACADESINE (AICA-RIBOSIDE) IMPROVES POSTISCHEMIC CARDIAC RECOVERY

To test if acadesine (5-aminoimidazole-4-carboxamide riboside), a purine precursor, has cardioprotective effects, 16 dogs were placed on total cardiopulmonary bypass and subjected to global myocardial ischemia. Hemodynamic recovery was compared between a control (n = 8) group receiving standard cardioplegia and an acadesine (n = 8) group pretreated with intravenous acadesine (2.5 mg . kg-1 . min-1 for 5 minutes, then 0.5 mg . kg-1 . min-1) before ischemia, during ischemia, and until 10 minutes after removal of the aortic cross-clamp. Additionally, in the acadesine group the cardioplegia also contained 20-mu-mol/L acadesine. While the dogs were on cardiopulmonary bypass, global warm myocardial ischemia was induced by aortic cross-clamping for 5 minutes under normothermic conditions to simulate an angioplasty accident. Five minutes after aortic cross-clamping, hypothermic cardioplegia (30 mL/kg) was administered. The left anterior descending coronary artery was occluded before the first infusion of cardioplegia to simulate poor cardioplegia delivery that can occur during an emergency coronary artery bypass procedure after an angioplasty accident. The left anterior descending artery occlusion was released, and additional cardioplegia (15 mL/kg) infusions were made every 30 minutes there-after during 120 minutes of cardioplegic ischemia. Thirty minutes after reperfusion, all animals in both groups were weaned from bypass and recovery data were obtained to compare with baseline preischemic values. There were no significant differences in heart rate, left atrial pressure, or systemic vascular resistance between groups after weaning from bypass. Peak developed pressure recovered to 79% +/- 19% (mean +/- standard deviation) of baseline in the acadesine group compared with 56% +/- 22% in the control group (p < 0.05). Additionally, recovery of mean arterial blood pressure (acadesine versus control: 71% +/- 15% versus 45% +/- 21%; p < 0.03), positive first derivative of left ventricular pressure (71% +/- 16% versus 35% +/- 13%; p < 0.01), and cardiac output (109% +/- 26% versus 53% +/- 39%; p < 0.01) were also significantly better with acadesine. Mixed venous oxygen saturation (preischemic baseline for both groups = 93%) was significantly lower in the control group (54% +/- 19%) compared with the acadesine group (90% +/- 8%) after bypass, a difference in extraction suggesting that oxygen delivery was better when acadesine was used. We conclude that acadesine is a promising cardioprotective agent for use during global ischemia.