Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was conducted to determine the long-term effect of flosequinan, a new orally administered arterial and venous dilator, on the clinical course of patients with moderate to severe congestive heart failure. Seventeen patients on chronic digitalis and diuretic therapy were randomized to receive either flosequinan (n = 9) or placebo (n = 8) in a double-blind fashion. Changes in symptomatology, exercise performance, and left ventricular function were assessed serially during the two-month treatment period. During the course of therapy, a modest improvement in the symptom scores and functional classification of the flosequinan-treated patients was observed. Flosequinan evoked a significant increase in maximal exercise capacity. While long-term flosequinan administration also effected a progressive increase in resting heart rate, it did not consistently improve indices of left ventricular systolic function. The addition of chronic vasodilator therapy with flosequinan to standard digitalis-diuretic regimens is capable of inducing clinical improvement in patients with moderate to severe chronic heart failure. Trials involving larger patient populations will be necessary to confirm the results of this preliminary study and to determine the extent of clinical improvement, subpopulations benefited, role in heart failure therapeutics, and so forth.
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PMID:Chronic vasodilator therapy with flosequinan in congestive heart failure. 218 66

Flosequinan, a new orally active vasodilator, and its sulfone metabolite were evaluated for inotropic activity in isolated ferret papillary muscles and pentobarbital anesthetized open-chest dogs. In vitro, flosequinan and its sulfone derivative increased tension development in a concentration-dependent manner (1-50 microM) in electrically stimulated papillary muscles pretreated with the beta-adrenergic blocking agent atenolol (2 microM). Peak increases in tension of 75 +/- 17%, and 111 +/- 46% with potencies (EC50) of 15 and 10 microM were observed for flosequinan and its metabolite, respectively. In vivo, flosequinan increased left ventricular dP/dtmax (74 +/- 12%) and right ventricular contractile force (CF) (104 +/- 10%) after administration of 1.875 mg/kg, i.v. Inotropic activity was dose-dependent and remained elevated for at least 60 min postinfusion. Flosequinan also increased heart rate (HR) (14 +/- 2%) and reduced mean arterial pressure (-9 +/- 3%). The i.v. potency of flosequinan (ED50 = 0.45 mg/kg) and its metabolite (ED50 = 0.38 mg/kg) were similar to that of the inotropic vasodilator amrinone (ED50 = 0.38 mg/kg). Inotropic activity was not significantly altered by pretreatment with propranolol (0.5 mg/kg) and atropine (1.0 mg/kg), further supporting the in vitro data indicating that flosequinan can directly stimulate myocardial contractility independent of beta-adrenergic receptor activation. Additional hemodynamic studies were conducted in an acute heart failure model produced by an overdose of propranolol. Flosequinan (2 mg/kg, i.v.) increased cardiac output (CO) (50 +/- 9%) and stroke volume (SV) (29 +/- 8%) while reducing total peripheral vascular resistance (TPR) (-36 +/- 4%), right atrial pressure (-62 +/- 5%), and left ventricular end-diastolic pressure (LVEDP) (-41 +/- 2%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Positive inotropic and hemodynamic properties of flosequinan, a new vasodilator, and a sulfone metabolite. 247 20

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.
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PMID:The effect of flosequinan in patients with acute-onset heart failure complicating acute myocardial infarction. 261 25

Twenty patients with severe chronic cardiac failure caused by ischaemic heart disease were treated with flosequinan 100 mg daily or placebo in addition to their existing treatment with diuretics and, in some, digoxin in a randomised double blind trial. After eight weeks of treatment, flosequinan significantly improved treadmill exercise time, increased peak achieved oxygen consumption, and improved the New York Heart Association symptom grade when compared with placebo. One patient in the placebo group died and another was withdrawn because heart failure worsened. One patient in the flosequinan group was lost to follow up but there were no other withdrawals. Flosequinan was well tolerated with few adverse effects, and it may prove to be a useful addition to diuretics and digoxin in the treatment of chronic cardiac failure.
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PMID:Effect of flosequinan on exercise capacity and symptoms in severe heart failure. 265 91

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.
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PMID:The effect of flosequinan in patients with heart failure of acute onset complicating acute myocardial infarction. 266 6

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.
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PMID:Effect of flosequinan in patients with acute-onset heart failure complicating acute myocardial infarction. 276 58

There is no single, simple test with which to evaluate new treatments for heart failure. Various methods need to be used, and a study of both the acute haemodynamic and longer term symptomatic effects of flosequinan, a new direct acting arteriolar and venous vasodilator, was therefore carried out in patients with heart failure. In one group of patients flosequinan increased cardiac output and caused a fall in pulmonary capillary wedge pressure, both effects lasting for 24 hours. In a double blind, placebo controlled study in another group flosequinan improved mean exercise tolerance from 9.9 to 12.7 minutes after four weeks of treatment. The drug also reduced perceived exertion during submaximal exercise and increased calf and therefore skeletal muscle blood flow. It reduced plasma renin activity and noradrenaline concentrations. Flosequinan possesses all the important properties of a drug likely to be of value in the treatment of heart failure.
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PMID:Flosequinan in heart failure: acute haemodynamic and longer term symptomatic effects. 304 7

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.
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PMID:Flosequinan induces hemodynamic improvement in heart failure complicating acute myocardial infarction. 316 79

We wished to provide comparative information regarding the direct effects of flosequinan, a novel quinolone under development for treating heart failure, on isolated human arterial, venous, and cardiac muscle. A similar assessment was made for four other agents--milrinone, ouabain, captopril and diltiazem--that have been used to treat heart failure patients, as well as for flosequinoxan, which is the primary metabolite of flosequinan. Flosequinan produced a potent and balanced relaxant effect on norepinephrine (NE)-contracted human arterial and venous smooth muscle, with IC25 values of 0.32 and 0.50 microM, respectively. At higher concentrations, flosequinan also produced a positive inotropic effect on human cardiac muscle (EC25 = 32 microM). A similar pattern of responses was observed with flosequinoxan. The pharmacologic profile obtained for the other agents examined differed from that observed with flosequinan and flosequinoxan in the following ways: Milrinone produced both vascular relaxant and positive inotropic effects, but at comparable concentrations; ouabain produced both vasoconstrictor and positive inotropic effects; diltiazem exerted a vascular relaxant effect at low concentrations and a negative inotropic effect at higher concentrations; and captopril had slight arterial relaxant and negative inotropic effects. These results demonstrate that the pharmacologic profile of flosequinan and flosequinoxan is unique as compared with that of other agents that have been used to treat patients with heart failure.
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PMID:Assessment of flosequinan's direct effect on human arterial, venous, and cardiac muscle: comparison with other classes of agents used to treat heart failure. 752 63

Two hundred and nine patients with moderate to severe chronic heart failure, all of whom remained symptomatic despite at least 80 mg of frusemide daily, were randomized to 12 months treatment with flosequinan or captopril. The patients were stratified into two groups, a treadmill group and a corridor walk test group, depending upon their exercise capability. Sixty-five out of 102 patients randomized to flosequinan and 43 out of 107 randomized to captopril (p < 0.001) did not complete the study. There was no difference between the groups in mortality: 19 patients died while taking flosequinan and 15 while taking captopril. Both drugs had similar effects on treadmill exercise tolerance; the mean increase at week 52 was 117 seconds in the flosequinan group and 156 seconds (p = 0.57) for the captopril group. For those patients stratified to the corridor walk test only, there was also very little difference in the improvement at 52 weeks; the mean increase for patients randomized to flosequinan was 61 meters and captopril was 75 meters (p = 0.65). However, when the walk tests from all patients are examined, captopril produced a significant improvement compared with flosequinan at week 52 (p = 0.015). Flosequinan has similar long-term efficacy to captopril but is associated with a higher incidence of adverse events.
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PMID:Long-term evaluation of treatment for chronic heart failure: a 1 year comparative trial of flosequinan and captopril. 774 61


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