POSITIVE INOTROPIC AND LUSITROPIC EFFECTS OF INTRAVENOUS FLOSEQUINAN IN PATIENTS WITH HEART-FAILURE

Objectives. This study was designed to assess the direct effects of flosequinan on myocardial function. Background. Flosequinan has been shown to improve symptoms and exercise tolerance in patients with heart failure. Although previous studies have established that flosequinan is a vasodilator, it is not known to what extent direct actions of the drug on myocardial contractility or diastolic properties contribute to its beneficial hemodynamic effects. Methods. Nitroprusside and intravenous flosequinan were administered sequentially to 18 patients with severe heart failure (New York Heart Association functional class III or IV, left ventricular ejection fraction 0.14 +/- 0.02). Micromanometer left ventricular pressure and radionuclide volume data were combined to construct pressure-volume loops during 1) a baseline period, 2) nitroprusside infusion, 3) a second baseline period, and 4) flosequinan infusion. Results. The peak rate of left ventricular pressure development increased from 899 +/- 84 to 1,070 +/- 94 mm Hg/s (p < 0.05) with flosequinan. The baseline left ventricular end-systolic pressure-volume relation was constructed in 15 patients from the two baseline pressure-volume loops and from that obtained during afterload manipulation with nitroprusside. During flosequinan administration, the relation between end-systolic pressure and volume was shifted upward and leftward, indicating enhanced contractility, in 14 of 15 patients (p < 0.001). The maximal rate of decrease in left ventricular pressure during isovolumetric relaxation increased in magnitude with flosequinan from 882 +/- 63 to 1,026 +/- 68 mm Hg/s (p < 0.05). Conclusions. These results indicate that intravenous flosequinan has positive inotropic and lusitropic effects in patients with heart failure. Further studies are needed to asses the direct myocardial effects of oral flosequinan.