Effect of a single oral dose of milrinone on left ventricular diastolic performance in the failing human heart

In 14 patients with severe congestive heart failure, left ventricular pressure (measured by tip manometer) and derived variables were measured before and every 10 minutes after administration of oral milrinone (10 mg) for 50 minutes along with measurements of coronary sinus blood flow and drug plasma levels. Arterial and coronary sinus catecholamines were measured only before and 50 minutes after milrinone. Left ventricular pressure, volume (as determined by angiography) and derived indexes were simultaneously assessed at matched atrial paced heart rate before and 60 minutes after milrinone. Three patients who did not achieve a therapeutic plasma level (less than 150 ng/ml) were excluded. Peak negative first derivative of left ventricular pressure (-dP/dt) progressively and significantly increased (10%) together with a decrease in the two exponential time constants of relaxation, namely, Tau 1 (19%) and Tau 2 (22%), which represent the fit for and after the first 40 ms, respectively. Coronary flow significantly increased by 43% within 30 minutes, whereas the decrease (-13%) in coronary vascular resistance failed to be statistically significant. No change occurred in catecholamine concentrations after milrinone. Peak filling rate significantly increased by 15%. Pressure-volume curves showed a leftward and, in four patients, a downward shift; a significant decrease in minimal left ventricular diastolic and end-diastolic pressures (by 55 and 38%, respectively) and in end-diastolic volume (18%) occurred. The constant of elastic chamber stiffness measured by the simple elastic model tended to decrease, but failed to achieve a statistically significant level. Thus, oral milrinone improved left ventricular early relaxation and filling as well as chamber distensibility. This global improvement of diastolic function makes milrinone a potentially useful drug in the oral treatment of heart failure.