The effects of amrinone on cardiac function, oxygen consumption and lactate production of an isolated, perfused, working guinea-pig heart.
Compared with isolated heart muscle and Langendorff preparations, the isolated, working heart preparation allows a more complete analysis of cardiac function and metabolism. We have studied the effects of amrinone 20 micrograms/ml and 200 micrograms/ml on the isolated perfused working guinea-pig heart. We have measured: heart rate (HR), mean systolic aortic pressure (SP), aortic flow (AF), coronary flow (CF), total cardiac output (CO), and calculated the stroke volume (SV) and the rate of external work (W). The rates of oxygen consumption (VO2) and lactate production (Lact) were also measured and the external efficiency (Eff) calculated. Hearts were allowed to fail spontaneously after work for 90 min. Amrinone was then added at the required concentration to the perfusion medium. Amrinone 20 micrograms/ml, increased AF, CF, CO, SV, W and VO2. HR was slightly but significantly increased. Lact and Eff were not altered. Amrinone 200 micrograms/ml substantially increased CF and VO2, but it increased slightly and not significantly AF, CO, SV and W, suggesting the predominance of the coronary vasodilating effect of amrinone at higher doses. Lact and Eff remained unchanged. The positive chronotropic effect was of the same magnitude than that observed with the lower dose. No arrhythmias occurred with either concentration. These results would suggest that amrinone is a positive inotropic drug with vasodilating properties at higher doses, and weak positive chronotropic effect. It stimulates aerobic but not anaerobic metabolism of the heart.
D000631:Aminopyridines / Q000494:pharmacology*; D000676:Amrinone; D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D007773:Lactates / Q000096:biosynthesis* / Q000378:metabolism; D019344:Lactic Acid; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects*; D013318:Stroke Volume / Q000187:drug effects
D000631:Aminopyridines; D002316:Cardiotonic Agents; D007773:Lactates; D019344:Lactic Acid; D000676:Amrinone