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.
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.
Emergency Unit, Shimane Medical University, Japan.
R
R
Murakami
K
K
Sano
Y
Y
Murakami
T
T
Shimada
S
S
Morioka
D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy; D006328:Cardiac Catheterization; D002306:Cardiac Volume / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D017023:Coronary Angiography; D003326:Coronary Circulation; D003327:Coronary Disease / Q000188:drug therapy; D003329:Coronary Vasospasm / Q000188:drug therapy; D003331:Coronary Vessels; D003971:Diastole; D005260:Female; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007093:Imidazoles / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D007267:Injections; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D011728:Pyridones / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D013318:Stroke Volume / Q000187:drug effects; D013599:Systole; D016277:Ventricular Function, Left / Q000187:drug effects*; D017725:Ventricular Pressure / Q000187:drug effects*
D002316:Cardiotonic Agents; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; C059498:olprinone