Effects of pimobendan and EGIS 9377, cardiotonic agents, and OG-VI, a nucleoside-nucleotide mixture, administered during reperfusion after ischemia on stunned myocardium in dogs

Background Pimobendan is a so-called calcium sensitizer that exerts a posit ive inotropic action. EGIS 9377 is synthesized as a calcium sensitizer. OG- VI is a nucleoside-nucleotide mixture that ameliorates the myocardial dysfu nction (myocardial stunning) after ischemia. Objective To determine whether administration of these agents after the ons et of reperfusion alter ischemia improves the condition of stunned myocardi um. Methods Dogs anesthetized with pentobarbital were subjected to 20 min ligat ion of left anterior descending coronary artery and then 60 min reperfusion . The corresponding vehicle, 0.3 and 1 mg/kg pimobendan, or 1 and 3 mg/kg E GIS 9377 was injected intravenously 30 min after the onset of reperfusion. Saline solution or 1.2 mu mol/kg per min OG-VI was infused for 30 min, star ting 30 min after the reperfusion. Shortening of myocardial segment was mea sured by sonomicrometry, The tissue levels of energy and carbohydrate metab olites in the 60 min-reperfused hearts were determined. Results Shortening of myocardial segments significantly decreased during is chemia, and returned toward preischemic level after reperfusion for all gro ups, although the contractile dysfunction still remained. Injections and in fusion of pimobendan, EGIS 9377, and OG-VI after the onset of reperfusion a meliorated the contractile dysfunction. Systemic vascular resistance was de creased by administrations of pimobendan and OG-VI. The levels of high-ener gy phosphates in 60 min-reperfused heart were not changed by either treatme nt. Conclusion Administration of pimobendan, EGIS 9377, and OG-VI ameliorate th e myocardial contractile dysfunction after ischemia even when these agents are administered after the onset of reperfusion, The increase in contractil e function due to these agents did not worsen the myocardial energy balance . Coronary Artery Dis 11:83-90 (C) 2000 Lippincott Williams & Wilkins.