Effects of intracoronary infusion of an inotropic agent, E-1020 (loprinone hydrochloride), on cardiac function: evaluation of left ventricular contractile performance using the end-systolic pressure-volume relationship

Int J Cardiol. 1995 Aug;51(1):57-63. doi: 10.1016/0167-5273(95)02397-f.

Abstract

The phosphodiesterase (PDE) III inhibitor, E-1020 (loprinone hydrochloride), has positive inotropic and vasodilating effects. This study evaluated the positive inotropic effect of intracoronary E-1020 in eight patients with coronary artery disease and hypertensive heart disease. A direct intracoronary infusion of the PDE III inhibitor minimizes its vasodilating effect. After baseline hemodynamic measurements and coronary arteriography, a micromanometer-tipped 8F conductance catheter was introduced into the left ventricle to determine the hemodynamic effects of E-1020. Saline and vehicle were infused into the left main coronary artery at a rate of 2 ml/min. The dose of intracoronary E-1020 increased from 2.5 to 5.0 and 7.5 micrograms/min. The inotropic effect of E-1020 was defined as the change in the slope of the end-systolic pressure-volume relationship (Emax), which was independent of afterload and preload. Emax significantly increased at infusion rates of 7.5 micrograms/min from control. Peak +dP/dt increased at an infusion rate of 5.0 micrograms/min or higher, while left-ventricular end-diastolic pressure (LVEDP) decreased significantly at a rate of 5.0 and 7.5 micrograms/min. Intracoronary infusion of E-1020 at a rate of 2.5 micrograms/min produced a plasma concentration of 20 ng/ml, which was identical to the minimum effective plasma concentration seen in previous study by intra venous infusion. However, at a plasma concentration of 20 ng/ml, E-1020 has more vasodilating effects than inotropic effects. Clinically, E-1020 appears to have a positive inotropic effect that depends on the extent of myocardial perfusion.

MeSH terms

  • Aged
  • Angina Pectoris / drug therapy
  • Cardiac Catheterization
  • Cardiac Volume / drug effects*
  • Cardiotonic Agents / administration & dosage
  • Cardiotonic Agents / blood
  • Cardiotonic Agents / therapeutic use*
  • Coronary Angiography
  • Coronary Circulation
  • Coronary Disease / drug therapy
  • Coronary Vasospasm / drug therapy
  • Coronary Vessels
  • Diastole
  • Female
  • Heart / drug effects*
  • Heart Rate / drug effects
  • Humans
  • Hypertension / drug therapy
  • Imidazoles / administration & dosage
  • Imidazoles / blood
  • Imidazoles / therapeutic use*
  • Injections
  • Male
  • Middle Aged
  • Myocardial Contraction / drug effects*
  • Phosphodiesterase Inhibitors / administration & dosage
  • Phosphodiesterase Inhibitors / blood
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Pyridones / administration & dosage
  • Pyridones / blood
  • Pyridones / therapeutic use*
  • Stroke Volume / drug effects
  • Systole*
  • Ventricular Function, Left / drug effects*
  • Ventricular Pressure / drug effects*

Substances

  • Cardiotonic Agents
  • Imidazoles
  • Phosphodiesterase Inhibitors
  • Pyridones
  • olprinone