Beneficial effects of adenosine A(2a) agonist CGS-21680 in infarcted and stunned porcine myocardium.
Although there are conflicting results on whether adenosine infusion during reperfusion alters infarct size, there are several reports that indicate adenosine A(2a) agonists reduce infarct size. There are also reports that the A(2a) agonist CGS-21680 increases cAMP and contractility in ventricular myocytes. The purpose of this study was to determine whether low-dose intracoronary infusions of CGS-21680 during reperfusion exert any beneficial effects in irreversibly and reversibly injured myocardium. Open-chest pigs were submitted to 60 min of coronary artery occlusion and 3 h of reperfusion. Treated pigs were administered intracoronary CGS-21680 (0.2 microg x kg(-1) x min(-1)) for the first 60 min of reperfusion. Pigs submitted to regional stunning (15 min ischemia) were treated with intracoronary CGS-21680 (0.15 microg x kg(-1) x min(-1)) after 2 h of reperfusion. In the infarct protocol, CGS-21680 reduced infarct size from 62 +/- 2% of the region at risk to 36 +/- 2%. In stunned myocardium, CGS increased load-independent regional preload recruitable stroke work and area by > or =70%, but the same infusion in normal myocardium was associated with no inotropic effect. Both beneficial effects were associated with little systemic hemodynamic effects. These findings suggest that reperfusion infusions of low doses of the A(2a) agonist CGS-21680 exert beneficial effects in reversibly and irreversibly injured myocardium.
Lasley
R D
RD
Department of Surgery, University of Kentucky College of Medicine, Lexington, Kentucky 40536, USA. rlasley@pop.uky.edu
Jahania
M S
MS
Mentzer
R M
RM
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology; D006321:Heart / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D009203:Myocardial Infarction / Q000188:drug therapy / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D017682:Myocardial Stunning / Q000188:drug therapy / Q000503:physiopathology*; D010627:Phenethylamines / Q000494:pharmacology*; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; D013552:Swine
D010627:Phenethylamines; D058906:Purinergic P1 Receptor Agonists; D043705:Receptor, Adenosine A2A; C061282:2-(4-(2-carboxyethyl)phenethylamino)-5'-N-ethylcarboxamidoadenosine; D000241:Adenosine