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)

Vasodilators used in chronic congestive heart failure are not optimal in that nitrates are predominant venodilators, prazosin is associated with tolerance development, and hydralazine produces chronic toxicity. Therefore, we studied the acute hemodynamic effects of a single dose of minoxidil in 18 patients with chronic left ventricular failure caused by ischemic or primary cardiomyopathy. Peak effects were observed 5 hours after single oral doses of minoxidil, averaging 15.3 +/- 1.4 mg (SEM). Heart rate rose slightly, from 85.4 +/- 2.9 to 90.9 +/- 3.2 beats/min, after minoxidil (p less than 0.02) and mean arterial pressure fell slightly, from 88.0 +/- 2.3 to 84.9 +/- 2.5 mm Hg (p less than 0.05). Cardiac index increased from 2.34 +/- 0.l4 to 2.95 +/- 0.29 l/min/m2 after minoxidil (p less than 0.02) and systemic vascular resistance fell from 19.6 +/- 1.5 to 15.0 +/- 1.3 units (p less than 0.01). Minoxidil did not affect right atrial, pulmonary arterial and pulmonary wedge pressures. Hemodynamic effects of minoxidil persisted for at least 8 hours after a single dose. Minoxidil appears to be an effective arterial dilating agent in patients with heart failure and resembles hydralazine in its actions. Because of its potency, prolonged duration of action and relatively low toxicity, minoxidil may be a useful vasodilator for heart failure. However, its long-term effect must be further evaluated.
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PMID:Effects of minoxidil on hemodynamics in patients with congestive heart failure. 700 52

Although hydralazine improves cardiac performance in patients with chronic left ventricular failure, its long-term clinical efficacy has not been established in controlled trials. We carried out a double-blind randomized trial of hydralazine (200 mg daily in 16 patients) versus placebo (16 patients) in patients with class III and IV symptoms while they were taking digitalis and diuretics. Maximal treadmill exercise time was determined prior to and at 4, 10, 18, and 26 weeks of hydralazine or placebo treatment; average follow-up was 20 weeks. We found no change in body weight, clinical class, resting heart rate and blood pressure, or heart size (by chest x-ray examination and echocardiogram) during treatment in either group. The total number of complicating clinical events was insignificantly fewer in the hydralazine treated group (8 vs 13). Control exercise duration in the hydralazine group averaged 259 +/- 21 seconds (SEM), and increased to 347 +/- 35 seconds at 4 weeks (p less than 0.01) and 421 +/- 38 seconds at 26 weeks (p less than 0.001). Exercise duration also increased significantly in the placebo group, from 271 +/- 30 seconds at control to 340 +/- 44 seconds at 4 weeks (p less than 0.02) and 339 +/- 46 seconds at 26 weeks (p less than 0.02). No differences between groups were significant. Left ventricular ejection fraction remained depressed and unchanged in both groups. Thus long-term vasodilator treatment with hydralazine alone is not significantly more effective than placebo in chronic heart failure.
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PMID:Hydralazine in the long-term treatment of chronic heart failure: lack of difference from placebo. 705 96

Seventeen patients with chronic congestive heart failure (CHF) were studied to assess the relationship of resting left ventricular function, as measured by noninvasive and invasive methods, to maximal exercise capacity, as measured by peak total body oxygen consumption (VO2). Supine basal plasma norepinephrine (NE) was also measured to evaluate its relationship to the severity of heart failure and to determine whether it may be a better predictor of exercise capacity in patients with CHF than the more commonly employed noninvasive and invasive tests of left ventricular function. Fourteen of the 17 patients underwent upright bicycle exercise (average peak VO2 10.60 +/- 1.40 ml/kg/min, +/- SEM) to their symptomatic maximum. There was no significant correlation between peak VO2 and the noninvasive measurements of left ventricular performance obtained at rest, including cardiothoracic ratio, left ventricular internal dimension by M-mode echo, percent shortening of the minor axis by M-mode echo, and radionuclide ejection fraction. Hemodynamic measurements were performed in 16 patients. The hemodynamic measurements at rest also failed to correlate with exercise capacity. The supine basal plasma NE, which was elevated in these 17 patients (612 +/- 100 pg/ml), had an inverse relationship with stroke work index (r - -0.70, p less than 0.01) and stroke index (r = -0.83, p less than 0.001) and a positive correlation with right atrial pressure (r = 0.81, p less than 0.001). Although both noninvasive and invasive measurements at rest failed to correlate significantly with peak VO2 during exercise, the plasma NE had a significant inverse correlation with peak exercise VO2 (r = -0.50, p less than 0.05). The basal supine plasma NE is therefore elevated in patients with CHF, is a marker for the severity of CHF as measured by hemodynamics performed at rest, and is a better predictor of exercise capacity than standard noninvasive and invasive tests performed at rest.
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PMID:Relationship of exercise capacity to resting left ventricular performance and basal plasma norepinephrine levels in patients with congestive heart failure. 712 85

The long-term effects of vasodilator therapy with oral hydralazine and long-acting nitrates were studied in 34 patients with refractory heart failure. Seven patients who had marginal hemodynamic improvement despite optimal hydralazine therapy were not maintained on vasodilators, and eight who had a favorable hemodynamic response subsequently discontinued hydralazine therapy because of side effects. Of these 15 patients, four (27%) died and 11 remained in New York Heart Association functional class II or IV at a mean follow-up of 10 +/- 2 months (SEM). The 19 patients who received chronic therapy for 8 +/- 2 months were divided into nine late responders (47%), who improved to functional class I or II, and 10 late nonresponders (53%), who remained in functional class III or IV. Only one of the nine late responders (11%) died, compared with seven of the 10 late nonresponders (70%) (p less than 0.01). The actuarially determined survival at 1 year was 100% for late responders and 13 +/- 12% for late nonresponders (p less than 0.01). No clinical variable could distinguish late responders from late nonresponders. Hemodynamic variables measured before vasodilator therapy showed that late responders had a lower mean right atrial pressure (8 +/- 1 vs 17 +/- 3 mm Hg, p less than 0.01) and lower mean pulmonary artery wedge pressure (20 +/- 2 vs 30 +/- 2 mm Hg, p less than 0.005), higher stroke, volume index (27 +/- 2 vs 20 +/- 1 ml/m2, p less than 0.005) and higher stroke work index (32 +/- 4 vs 19 +/- 2 g-m/m2, p less than 0.01) than late nonresponders. There were no significant differences in the acute response to vasodilators between the two groups. We conclude that (1) a substantial portion of patients with refractory congestive heart failure either do not have a beneficial response to vasodilator therapy or discontinue it because of side effects; (2) about half of the patients who are maintained on chronic vasodilator therapy (or about one-fourth of the patients in whom therapy is initiated) had sustained clinical benefit; and (3) the initial hemodynamics, but not the clinical variables, are predictive of late mortality and late clinical response. Patients with evidence of more severe left ventricular dysfunction have an unfavorable course.
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PMID:Results of long-term vasodilator therapy in patients with refractory congestive heart failure. 726 Dec 82

Although the relationship between blood pressure and cardiac performance has been widely recognized, there are few published clinical observations concerning the effect of blood pressure control on cardiac function. We evaluated the effect of prazosin, an antihypertensive agent which also improves hemodynamic measurements in normotensive patients with heart failure, in 16 patients with moderate hypertension and reduced ejection fractions. Therapy with digoxin and diuretics was continued throughout the study, but other antihypertensive agents were withdrawn at least one week prior to the initiation of the study. Measurements of ejection fraction, cardiothoracic ratio and the duration of maximal treadmill exercise were made before and after two months of antihypertensive therapy with prazosin. On prazosin, blood pressure fell from a mean of 169/103 to 141/84. Excellent control was achieved in 13/16 patients and significant reductions were noted in the remaining three. Concomitantly, ejection fraction rose from .38 +/- .02 (SEM) to .43 +/- .03 (P less than .02), cardiothoracic ratio decreased from .55 +/- .02 to .53 +/- .02 (P less than .05) and exercise capacity increased from 9.2 +/- 0.9 to 11.9 +/- 1.1 minutes (P less than .005). Prazosin was well tolerated except in one patient who experienced worsening angina. These findings emphasize the importance of rigorous blood pressure control in hypertensive patients with left ventricular dysfunction and indicate that prazosin is effective in this setting.
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PMID:Antihypertensive therapy with prazosin in patients with left ventricular dysfunction. Improvement in cardiac performance and exercise tolerance. 730 90

The haemodynamic effects and pharmacokinetics of single intravenous doses of tolmesoxide, a new vasodilator agent, were studied in 6 patients with severe cardiac failure secondary to ischaemic cardiomyopathy and refractory to conventional therapy. The mean (+ SEM) baseline cardiac index (CI) and pulmonary artery diastolic pressure (PADP) were 1.7 +0.11/min/m2 and 30.5 +4.1 mm Hg respectively. The mean % rise in CI was 78.8 +23.3 and the mean % fall in PADP was 35.2 +5.2. The mean half life of tolmesoxide in these patients was markedly prolonged at 15.6 +6.6h. Side effects were minimal - vomiting was seen in 1 patient. This agent warrants further study in the long term management of refractory cardiac failure.
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PMID:Clinical pharmacology of tolmesoxide in refractory heart failure. 731 77

The acute haemodynamic effects of nifedipine (10 mg sublingually) and isosorbide dinitrate (5 mg sublingually) were compared in 13 patients with heart failure due to acute myocardial infarction. Nifedipine induced a significant reduction in systolic (from 122 +/- 5 to 107 +/- 3 mm Hg: mean +/- SEM; P less than 0.002) and diastolic blood pressure (from 85 +/- 3 to 75 +/- 2 mm Hg; P less than 0.01). Heart rate did not change significantly, nor did mean right atrial pressure. The mean pulmonary arterial pressure was lowered from 31 +/- 2 to 27 +/- 2 mm Hg (P less than 0.005). The left ventricular filling pressure decreased from 24 +/- 1 to 19 +/- 1 mm Hg (P less than 0.0001). A significant increase in cardiac index (from 2.33 +/- 0.13 to 2.69 +/- 0.15 l/min per m2; P less than 0.001) and in stroke volume index (from 24 +/- 2 to 28 +/- 2 ml/beats per m2; P less than 0.005) was registered. Systemic vascular resistance fell from 1742 +/- 145 to 1308 +/- 85 dynes/sec per cm-5 (P less than 0.00005). After isosorbide dinitrate was administered a significant reduction in mean right atrial pressure (from 9.5 +/- 1.6 to 5.1 +/- 1.2 mm Hg; P less than 0.0001), in mean pulmonary arterial pressure (from 32 +/- 1 to 23 +/- 1 mm Hg; P less than 0.00001) and in left ventricular filling pressure (from 23 +/- 1 to 16 +/- 1 mm Hg; P less than 0.0001) was seen. No significant change in systolic and diastolic blood pressure, heart rate, cardiac index, stroke volume index and systemic vascular resistance was registered. No side-effects were seen after nifedipine and isosorbide dinitrate were administered.
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PMID:Comparison of acute haemodynamic effects of nifedipine and isosorbide dinitrate in patients with heart failure following acute myocardial infarction. 733 18

The effect of beta-adrenergic receptor downregulation on peak exercise response in patients with heart failure has not been directly investigated. Seventy-two patients with idiopathic dilated cardiomyopathy who had a mean ejection fraction of 23 +/- 1% (mean +/- SEM) and New York Heart Association class II or III symptoms were investigated. Subjects underwent maximal exercise testing on a bicycle or a treadmill, hemodynamic assessment by right heart catheterization, and measurement of total beta-adrenergic receptor density by 125I-iodocyanopindolol binding performed in the right ventricular endomyocardial biopsy tissue and in peripheral lymphocytes. Endomyocardial biopsy beta-adrenergic receptor density (Bmax) was markedly decreased (45 +/- 2 fmol/mg), and significantly lower than lymphocytes Bmax (107 +/- 14 fmol/mg; p < 0.05). By univariate analysis, all exercise variables correlated significantly with biopsy tissue Bmax but not with lymphocyte Bmax. Maximal exercise oxygen consumption (VO2max) yielded the highest correlation with Bmax (r2 = 0.61, p < 0.001). By stepwise regression analysis, VO2 max, delta heart rate x systolic blood pressure, and ejection fraction were all independently related to Bmax. Myocardial beta-adrenergic receptor downregulation is likely to be partially responsible for the reduced chronotropic and inotropic responses to peak exercise in patients with mild to moderate symptomatic heart failure due to idiopathic dilated cardiomyopathy.
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PMID:Role of beta-adrenergic receptor downregulation in the peak exercise response in patients with heart failure due to idiopathic dilated cardiomyopathy. 750 9

Chronic rapid right ventricular pacing (RRVP) at 250 beats/min produces low cardiac output (CO) heart failure, marked reduction in total vascular capacitance, and a shift in volume centrally. The effect of converting enzyme inhibition with captopril on cardiac preload was investigated in this model of heart failure. Eight splenectomized dogs were treated with captopril (6.4 mg/kg daily) for 3 days before and 35 +/- 3 days (mean +/- SEM) after continuous RRVP was initiated and the outcome was compared with that of 5 untreated dogs subjected to RRVP for 32 +/- 3 days. Similar reductions in systemic arterial pressure (Psa) and CO and increases in right atrial pressure (Pra) and total peripheral resistance (TPR) were noted in both groups, however, pulmonary capillary wedge pressure (Ppcw) was higher in the untreated group (18.4 +/- 1.6 vs. 12.1 +/- 2.0 mm Hg). Total vascular compliance and capacitance was estimated from mean circulatory filling pressures (Pmcf) at different blood volumes (TBV) during transitory cardiac arrests with acetylcholine (ACh). Pmcf after chronic RRVP was higher in untreated animals (12.6 +/- 1.9 vs. 8.4 +/- 0.7 mm Hg) and compliance was lower (1.9 +/- 0.2 vs. 2.6 +/- 0.2 ml/mm Hg/kg). Total vascular capacitance at a Pmcf of 6 mm Hg was lower in untreated animals (50 +/- 6 vs. 68 +/- 3 ml/kg). Central vascular capacitance was also lower in untreated animals because Ppcw was higher and central blood volume (CBV) as a proportion of TBV was higher (21 +/- 3 vs. 15 +/- 2%). Four of 5 untreated and 1 of 8 treated dogs had severe ascites.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of captopril treatment on total and central vascular capacitance in dogs with chronic heart failure. 752 90

Attenuation of the increase in blood flow caused by acetylcholine in the peripheral vasculature and coronary circulation of patients with heart failure has been interpreted as an impairment of endothelium-dependent vasodilation. The aim of this study was to compare in man the effects of acetylcholine, which also has endothelium-independent actions, with substance P, which appears to be a pure endothelium-dependent vasodilator, on epicardial and resistance coronary arteries in patients with idiopathic dilated cardiomyopathy. The effects of intracoronary acetylcholine (10(-7) M and 10(-6) M) and substance P (5, 10 and 25 pmol.min-1) on epicardial coronary artery diameter and coronary blood flow velocity were measured with an intracoronary Doppler flow probe and quantitative coronary angiography in 11 patients with idiopathic dilated cardiomyopathy and 10 control subjects. Epicardial coronary artery diameter did not change with acetylcholine but increased significantly with substance P in both groups (cardiomyopathy patients: 3.3 +/- 0.2 mm (mean +/- SEM) at baseline vs 3.9 +/- 0.2 mm with substance P25 pmol.min-1, P < 0.01; controls: 3.1 +/- 0.2 mm at baseline vs 3.9 +/- 0.3 mm with substance P25 pmol.min-1, P < 0.05). Coronary flow ratios with acetylcholine were lower in cardiomyopathy patients (10(-7) M: 1.4 +/- 0.1 vs 2.3 +/- 0.4, P = 0.05; 10(-6) M: 1.8 +/- 0.2 vs 3.2 +/- 0.5, P = 0.05 vs controls).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of intracoronary substance P and acetylcholine on coronary blood flow in patients with idiopathic dilated cardiomyopathy. 753 Jun 61


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