Influence of dipyridamole on infarct size and on cardiac nucleoside content following coronary occlusion in the dog.
The effects of 3 different doses (0.02, 0.1, 0.5 mg/kg/h) of dipyridamole on myocardial infarct size were evaluated in pentobarbital anesthetized open-chest dogs following sequential coronary occlusion of two medium sized coronary arteries in the same heart. The first coronary occlusion produced a control infarct, the other a test infarct under the influence of the drug. Dipyridamole infusion was started 10 min before the second occlusion at a rate of 0.02 (group A, n = 9), 0.1 (group B, n = 10) or 0.5 (group C, n = 9) mg/kg/h respectively and continued to the end of reperfusion (90 min). Biopsy samples were obtained at the end of each occlusion period and at the end of the second reflow period. Infarct size was determined using post mortem angiography and pNBT staining. Control and treated infarct sizes, expressed as a percentage of the perfusion area, were 21.9 +/- 5.4% vs. 25.2 +/- 7.7% in group A (n = 9), 21.8 +/- 7.3% vs. 18.3 +/- 5.2% in group B (n = 9), and 22.3 +/- 7.7% vs. 16.2 +/- 4.8% in group C (n = 8). There were no significant differences between control and treated infarct sizes in the 3 groups. After 90 min coronary occlusion tissue adenosine contents in the ischemic myocardium were significantly higher (42 +/- 7 nmol/gww in group C and 40 +/- 5 nmol/gww in group B) than those in the nonischemic myocardium, and dipyridamole enhanced these levels (395 +/- 6 nmol/gww in group C: p less than 0.01, 55 +/- 10 nmol/gww in group B). Dipyridamole did not affect the tissue inosine levels in the ischemic myocardium after 90 min coronary occlusion. ATP and creatine phosphate levels were not affected by dipyridamole during ischemia or during reflow. The accumulated adenosine was not phosphorylated to AMP and on to ATP upon reperfusion.
D000241:Adenosine / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003327:Coronary Disease / Q000150:complications; D004176:Dipyridamole / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007288:Inosine / Q000032:analysis; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology*; D009206:Myocardium / Q000032:analysis; D010725:Phosphocreatine / Q000032:analysis
D010725:Phosphocreatine; D007288:Inosine; D004176:Dipyridamole; D000241:Adenosine