FLOSEQUINAN - A VASODILATOR WITH POSITIVE INOTROPIC ACTIVITY

Flosequinan is an oral arterial and venous vasodilator that is currently under investigation for the treatment of congestive heart failure. The effects of flosequinan on ventricular performance and myocardial contractility were studied in 10 patients with severe congestive heart failure during right and left cardiac catheterization. Sixty minutes after a 100 mg oral dose of flosequinan, the peak rate of rise in left ventricular pressure (dP/dt) increased from 940 +/- 180 to 1050 +/- 240 mm Hg/sec (p < 0.05), while left ventricular end-diastolic pressure decreased from 32 +/- 5 to 26 +/- 8 mm Hg (p < 0.05), and cardiac index increased (2.1 +/- 0.4 to 2.3 +/- 0.5 L/min/m2, (p < 0.05). The mean pulmonary artery pressure and vascular resistance decreased from 40 +/- 8 to 33 +/- 12 mm Hg (p < 0.05) and from 330 +/- 240 to 290 +/- 170 dyne-sec/cm5 (p < 0.05), respectively. Heart rate, mean aortic pressure, right atrial pressure, systemic vascular resistance, and serum norepinephrine levels did not change significantly. The increase in left ventricular peak dP/dt that was concomitant with a decrease in left ventricular end-diastolic pressure, and no change in systemic arterial pressure or sympathetic tone, argue for a direct positive inotropic effect of flosequinan.