Hemodynamic effects of prenalterol in patients with ischemic heart disease and congestive cardiomyopathy.

The hemodynamic effects of a new,/3 agonist, prenalterol, were studied in 13 patients with severe left ventricular failure (New York Heart Association functional class III or IV). Seven patients had ischemic heart disease and six congestive cardiomyopathy. Left ventricular function was studied by cath- eter-tip manometer measurements of left ventricular pressure and simultaneous pressure-volume analysis. To minimize rate-related changes in left ventricular function, studies were performed during constant atrial pacing at 100 beats/min unless the intrinsic heart rate was higher. A 12-mg i.v. dose of prenalterol was infused. The maximum rate of pressure development (peak positive dP/dt) increased from 1084 + 95 mm Hg/sec (mean + SEM) to 1493 176 mm Hg/sec (p < 0.005). Stroke volume and ejection fraction also increased. Left ventricular relaxation, measured as the maximum rate of pressure fall (peak negative dP/dt) improved from -1011 91 to -1202 + 119 mm Hg/sec. Alteration in the time constant of pressure fall (T) also suggested improved relaxation, as it decreased from 71.8 7.7 to 48.5 6.3 msec. Prenalterol also decreased left ventricular stiffness, particularly in patients with very stiff ventricles. As a positive inotropic agent, prenalterol increased left ventricular mean power from 5.2 0.4 to 6.8 0.7 W and left ventricular stroke work from 8.3 + 0.7 to 10.2 1.0 W-sec (p < 0.005). Left ventricular stress did not change significantly. The ratio of the diastolic pressure-time index to the systolic pressure-time index increased significantly (0.53 0.04 and 0.63 0.04, respectively, p < 0.005). Despite different absolute values, the percent changes of left ventricular function were similar in both groups. We conclude that even in patients with severe left ventricular failure, ventricular systolic and diastolic function can be improved by prenal- terol. As a result of improved contractility, relaxation and stiffness, left ventricular filling pressure de- creased. The data indicate a favorable effect on the balance between myocardial oxygen supply and demand. Intravenous prenalterol is a promising new drug for patients with severe heart failure. PRENALTEROL, the levo-isomer of S-(-)-l-(4 hy- droxyphenoxy)-3-isopropyl-amino-propanol-2 hydro- chloride, is a new selective /Th adrenoceptor agonist with little chronotropic effect demonstrable in animal studies.1 When administered orally or intravenously, prenalterol enhanced left ventricular contractility in humans.3 Dose-dependent shortening of electrome- chanical systole and preejection time have been re- ported.3'4 In patients who had suffered acute myocar- dial infarction, prenalterol increased left ventricular contractility without altering diastolic blood pressure and with little change in heart rate or pulse pressure.5.6