Acute hemodynamic effects of MDL19205 on conscious dogs with mitral regurgitation

Abstract

To assess the effects of MDL19205, a combined inotropic-vasodilating agent, or an inodilator, on the left ventricle with subacute volume overload due to mitral regurgitation (MR), seven dogs were instrumented with a left ventricular (LV) micromanometer and a pair of ultrasonic crystals for the measurement of LV circumferential segment length. After examining the effects of this drug in the normal hearts, its effects were observed in the same dogs in which MR was produced by sectioning chordae tendineae. Mitral regurgitation caused increases in LV peak dP/dt (2,384 +/- 256 to 3,090 +/- 622 mmHg/sec; p less than 0.05), mean circumferential shortening velocity (Vcf; 1.41 +/- 0.25 to 1.85 +/- 0.20 sec-1; p less than 0.05), LV end-diastolic pressure (LVEDP; 8.2 +/- 1.6 to 15.8 +/- 3.7 mmHg; p less than 0.001), and LV end-diastolic length (LVEDL; 10 to 10.6 +/- 0.2mm; p less than 0.01). The dogs were intravenously administered MDL19205 7 to 14 days after they had completely recovered from the first and second operations. With 3 mg/kg of MDL19205, peak changes of hemodynamic indices occurred within 5 minutes in the hearts with MR LV dP/dt and mean Vcf significantly rose (from 3,090 +/- 622 to 5,356 +/- 811 mmHg/sec; p less than 0.001, 1.85 +/- 0.20 to 2.65 +/- 0.36 sec-1, p less than 0.001). LVEDP and LVEDL were returned to the control values obtained in the normal hearts (15.8 +/- 3.7 to 6.4 +/- 2.4 mmHg; p less than 0.001, 10.6 +/- 0.2 to 10 +/- 0.4; p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)