Effects of molsidomine and dopamine infusion on the size of canine experimental myocardial infarct

Summary The effects of i.v. molsidomine and dopamine infusion on mean haemodynamic changes, myocardial oxygen consumption (pressure-rate-product), and ultimate infarct size were studied in pentobarbital-anaesthetized, open-chest dogs and compared to those occurring in dogs receiving saline infusion. Either agent was administered in a separate setting. Haemodynamic variables and oxygen consumption were determined during a 6-h period after ligation of the left anterior descending coronary artery and collected at 1-h intervals. Infarct size was determined by post-mortem nitroblue tetrazolium stain of intracellular lactic dehydrogenase enzymes. Coronary artery ligation during saline infusion (n=8) resulted in decreased blood pressure and cardiac output, whereas heart rate, systemic peripheral resistance, end-diastolic filling pressure and myocardial oxygen consumption increased. Infarct size amounted to 24.2±3.2% (i. e., 23.8±3.1 g) of left ventricular mass. Infusion of 1.4 g/kg/min molsidomine (n=8) produced significant fall of blood pressure, cardiac output, filling pressure and oxygen consumption while heart rate and peripheral resistance were unaffected. The infarct volume was reduced to 49% (P<0.01) of that observed in saline controls. The administration of 3 g/kg/min dopamine (n=8) elevated blood pressure and cardiac output initially with a subsequent reduction of either parameter. Arteriolar vascular resistance and oxygen consumption increased but filling pressure remained unchanged. Infarct size was not different from saline controls. Infusion of 6 g/kg/min dopamine, however, significantly increased blood pressure, heart rate, and peripheral resistance. Cardiac output and filling pressure fell and myocardial oxygen consumption rose. The histochemically measured final infarct was reduced to 13.5±1.8% of left ventricle (i. e., 16.2±2.2 g, P<0.05 vs saline control), but the hearts were edematous and haemorrhagic. Therapy with molsidomine appears promising in the treatment of clinical myocardial infarction with haemodynamic sequellae. The safe use of therapy with higher dopamine doses in patients with acute myocardial infarction, however, awaits further investigation.Part of the dopamine experiments were done at Bayer AG, Institut für Pharmakologie