Haemodynamic Dose–Response Effects of Intravenous Indoramin in Acute Heart Failure Complicating Myocardial Infarction

Abstract

The haemodynamic dose-response effects of intravenous indoramin were evaluated in 12 patients with acute heart failure (pulmonary artery occluded pressure of greater than 20 mm Hg) complicating a recent myocardial infarction. Following a 1-h control period with confirmed stable haemodynamics, the effects of three intravenous bolus doses of indoramin (0.125, 0.125, and 0.25 mg/kg at 15-min intervals) were determined in the 10- to 15-min period following each intravenous injection. Plasma drug concentrations rose with the administered dose and were in the previously established therapeutic range. Ten patients tolerated all three doses of the drug; two patients were withdrawn following the second dose owing to clinically evident hypotension (systolic blood pressure of less than 100 mm Hg). Indoramin resulted in progressive falls in systolic, diastolic, and mean systemic arterial pressures (p less than 0.01) without change in cardiac index. There was a dose-related reduction in the heart rate (0.5 mg/kg; -7 beats/min; p less than 0.01). The left ventricular filling pressure showed a significant and quadratic reduction over the dose range (0.5 mg/kg, -5 mm Hg; p less than 0.01). The systemic vascular resistance index was reduced (-333 dynes X s X cm-5 X m2; p less than 0.001) and the stroke volume index increased (+3 ml/m2; p less than 0.05) following the maximum cumulative dosage. These data established the therapeutic safety of indoramin (0.125-0.5 mg/kg) in acute heart failure following myocardial infarction. An improvement in cardiac performance in these patients was compatible with circulatory actions on both cardiac preload and afterload.