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 mumol/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 thereafter 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 less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Bolling
S F
SF
Department of Surgery (Thoracic Surgery), University of Michigan, Ann Arbor.
Groh
M A
MA
Mattson
A M
AM
Grinage
R A
RA
Gallagher
K P
KP
D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D003250:Constriction; D001026:Coronary Artery Bypass; D004285:Dogs; D006321:Heart / Q000187:drug effects*; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D009200:Myocardial Contraction / Q000187:drug effects; D012263:Ribonucleosides / Q000627:therapeutic use*; D014655:Vascular Resistance / Q000187:drug effects
D012263:Ribonucleosides; D000620:Aminoimidazole Carboxamide; C011651:acadesine