flosequinan and Myocardial-Infarction

We studied the hemodynamic effect of a single dose of the new direct-acting vasodilator, flosequinan, in 18 patients with severe heart failure of acute onset complicating acute myocardial infarction, which was resistant to high doses of diuretics, nitrates and dobutamine given intravenously. Flosequinan was added to conventional therapy at 3.5 +/- 0.8 days from the infarction, in the form of a single oral dose of 100 mg. Hemodynamic measurements were performed every hour for 4 hours after the administration, without any other drug being added. The infusion rate of nitrates was kept constant. Flosequinan produced hemodynamic improvement in this group. The effect peaked at 2 hours and remained at this level at 4 hours. Pulmonary capillary wedge pressure decreased from 27.6 +/- 4.3 to 16.8 +/- 2.8 mm Hg and cardiac output increased from 3.5 +/- 0.3 to 4.1 +/- 0.4 l/min (P less than 0.001). Pulmonary arterial and right atrial pressures and systemic and pulmonary vascular resistances were also significantly reduced. Heart rate and mean systemic arterial pressure were not significantly altered. Administration of flosequinan was not associated with symptomatic hypotension, cardiac arrhythmias or other adverse events. We conclude that flosequinan is effective in producing acute hemodynamic improvement in patients with heart failure, complicating acute myocardial infarction, which is resistant to conventional therapy. Flosequinan is safe and well tolerated. Studies for longer time periods are indicated.

Topics: Acute Disease; Adult; Aged; Clinical Trials as Topic; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Quinolines; Vasodilator Agents

We studied the hemodynamic effect of a single dose of the new direct-acting vasodilator, flosequinan, in 25 patients with severe acute-onset heart failure complicating acute myocardial infarction, which was resistant to high doses of diuretics, nitrates and dobutamine given intravenously. Flosequinan was added to conventional therapy within 3.7 +/- 0.8 days of the infarction in the form of a single oral dose of 100 mg. Hemodynamic monitoring was performed every hour for 4 hours after the administration, without any other drug being added. Flosequinan produced hemodynamic improvement in all patients. The effect peaked at 1 to 2 hours and remained at this level at 4 hours. Pulmonary capillary wedge pressure decreased from 28.4 +/- 4.5 to 17.8 +/- 5.7 mmHg and cardiac output increased from 3.5 +/- 0.3 to 4.0 +/- 0.4 L/min (p less than 0.05 for both). Pulmonary arterial and pulmonary vascular resistances were also significantly reduced. Heart rate was not significantly altered. Mean systemic arterial pressure was slightly but not significantly reduced. Administration of flosequinan was not associated with symptomatic hypotension, cardiac arrhythmias or other adverse events and the hemodynamic effect was not related to the pre-treatment serum sodium concentration. We conclude that flosequinan is effective in producing acute hemodynamic improvement in patients with heart failure complicating acute myocardial infarction which is resistant to conventional therapy. Flosequinan is well tolerated in this group of patients and therefore further studies to determine the duration of action of the drug in this condition are appropriate.

Topics: Acute Disease; Aged; Cardiac Output; Drug Evaluation; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Pulmonary Circulation; Pulmonary Wedge Pressure; Quinolines; Vascular Resistance; Vasodilator Agents

We studied the hemodynamic effect of a single dose of the new direct-acting vasodilator, flosequinan, in ten patients with severe acute-onset heart failure complicating acute myocardial infarction (MI) resistant to high iv doses of diuretics, nitrates, and dobutamine. Flosequinan was added to conventional therapy at 3.8 +/- 0.5 days after infarction in the form of a single 100-mg oral dose. Hemodynamic measurements were performed every hour for 4 h after administration, without any other drug being added. The nitrate infusion rate was kept constant. Flosequinan produced hemodynamic improvement in this group. The effect peaked at 1 to 2 h and remained at this level at 4 h. Pulmonary capillary wedge pressure decreased from 27.2 +/- 5.4 to 16.4 +/- 3.0 mm Hg, and cardiac output increased from 3.5 +/- 0.3 to 4.1 +/- 0.4 L/min (p less than .001 for both). Cardiac index, stroke index, and left ventricular stroke work index were significantly increased. Pulmonary arterial and right atrial pressures, and systemic and pulmonary vascular resistances were also significantly reduced. Heart rate was not significantly altered. Mean systemic arterial pressure was slightly reduced. Flosequinan administration was not associated with symptomatic hypotension, cardiac arrhythmias, or other adverse events, and the hemodynamic effect was not related to the pretreatment serum sodium concentration. We conclude that flosequinan is effective in producing acute hemodynamic improvement in patients with heart failure complicating acute MI resistant to conventional therapy.

Topics: Administration, Oral; Aged; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Quinolines; Vasodilator Agents

The hemodynamic effects of a single dose of flosequinan, a new balanced vasodilator, were studied in twelve patients with severe acute onset heart failure complicating acute myocardial infarction. Flosequinan was added to conventional therapy within 3.8 +/- 0.5 days of the infarction, in the form of a single oral dose of 100 mg in ten of the patients. In the remaining two, reinfarction developed on the sixth day and they received flosequinan immediately thereafter. Hemodynamic monitoring was performed for four hours after the administration, without any other drug being given. Flosequinan produced hemodynamic improvement in all patients. The effect peaked at one to two hours and remained at this level at four hours. Pulmonary capillary wedge pressure decreased from 27.4 +/- 5.0 to 16.5 +/- 2.9 mm Hg and cardiac output increased from 3.5 +/- 0.3 to 4.1 +/- 0.4 l/min (p less than 0.001 for both). Pulmonary arterial and right atrial pressures and systemic and pulmonary vascular resistances were also significantly reduced. Heart rate was not significantly altered (from 84.0 +/- 4.5 to 87.4 +/- 4.6). Mean systemic arterial pressure was slightly reduced. Administration of flosequinan was not associated with any adverse effects and the hemodynamic effect was not related to the pre-treatment serum sodium concentration. We concluded that flosequinan can produce acute hemodynamic improvement in patients with heart failure, complicating acute myocardial infarction. The drug is well tolerated.

Topics: Adult; Aged; Aged, 80 and over; Drug Therapy, Combination; Female; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Quinolines; Vasodilator Agents