Cardioprotection with adenosine-regulating agent, GP531: effects on no-reflow, infarct size, and blood flow following ischemia/ reperfusion in the rabbit.

Abstract

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 microg/kg and 10 microg/kg per minute or 2100 microg/kg and 30 microg/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.

• Authors: Sharon L Hale, Robert A Kloner
• Journal: Journal of cardiovascular pharmacology and therapeutics (J Cardiovasc Pharmacol Ther) Vol. 15 Issue 1 Pg. 60-7 (Mar 2010) ISSN: 1940-4034 [Electronic] United States
• PMID: 20133497 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Deoxyribonucleosides
• GP 531
• Aminoimidazole Carboxamide
• Adenosine

Topics

• Adenosine (pharmacology)
• Aminoimidazole Carboxamide (analogs & derivatives, pharmacology)
• Analysis of Variance
• Animals
• Deoxyribonucleosides (pharmacology)
• Disease Models, Animal
• Hemodynamics (drug effects)
• Male
• Myocardial Infarction (prevention & control)
• Myocardial Ischemia
• Myocardial Reperfusion Injury (drug therapy, physiopathology)
• Rabbits
• Random Allocation