Acute hemodynamic effects of MDL 19205 on conscious dogs with mitral regurgitation

Summary

To assess the effects of MDL 19205, 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<0.05), mean circumferential shortening velocity (Vcf; 1.41±0.25 to 1.85±0.20 sec^-1; p<0.05), LV end-diastolic pressure (LVEDP; 8.2±1.6 to 15.8±3.7 mmHg; p<0.001), and LV end-diastolic length (LVEDL; 10 to 10.6±0.2mm; p<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<0.001, 1.85±0.20 to 2.65±0.36 sec^-1, p<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<0.001, 10.6±0.2 to 10±0.4; p<0.01). While MDL19205 increased the heart rate in the normal hearts (98±9 to 118±9 beats/min; p<0.05), it had no effect on those with MR (109±10 to 106±17 beats/min). This study suggests that MDL19205 increases LV contractile indices and decreases preload indices in subacute MR, as observed in the normal heart. In addition, it does not increase heart rate in MR while it increases in the normal heart. Thus, MDL19205 is a promising inodilator for the treatment of hemodynamic abnormalities resulting from subacute MR.