期刊
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY AND THERAPEUTICS
卷 15, 期 1, 页码 60-67出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/1074248409357742
关键词
GP531; adenosine-regulating agent; myocardial infarct size; no-reflow
资金
- Pericor Therapeutics [GP531]
GP531, a potent, second-generation adenosine-regulating agent, is pharmacologically silent under basal conditions but increases localized endogenous adenosine during ischemia. GP531 improves functional recovery after myocardial ischemia, but its effects on infarct size and no-reflow have not been reported. The objective was to determine whether GP531 reduces necrosis and the anatomic no-reflow defect and to evaluate its effects on regional myocardial blood flow (RMBF). GP531 was given as a loading dose plus infusion at 2 doses (700 mu g/kg and 10 mu g/kg per minute or 2100 mu g/kg and 30 mu g/kg per minute) or vehicle, starting 12 minutes before a 30-minute coronary occlusion and throughout 3 hours reperfusion in rabbits. Risk zone was delineated by blue dye, necrosis by tetrazolium staining, RMBF by radioactive microspheres, and no-reflow defect by thioflavin S. The extent of the ischemic risk zone was similar in all groups. Low-dose GP531 reduced infarct size by 34% (0.33 +/- 0.4 of the risk zone) compared with vehicle (0.50 +/- 0.4, P < .01) and reduced the extent of the anatomic no-reflow zone by 31% compared with vehicle (0.25 +/- 0.3 of the risk zone vs 0.36 +/- 0.4 in the vehicle group, P < .05). Infarct size and zone of no-reflow in the high dose were reduced by 22% and 16%, respectively (P = NS vs the other 2 groups). GP531 did not affect hemodynamics or blood flow. Thus, GP531 was effective at the lower dose evaluated in this study, reducing the severity of ischemic/reperfusion injury, without inducing the adverse hemodynamic effects associated with adenosine administration such as bradycardia and hypotension.
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