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)

Captopril, the competitive inhibitor of angiotensin-converting enzyme, has proved efficient in the treatment of arterial hypertension and heart failure. Its use is generally associated with low incidence of adverse reactions and hepatic injury has not been emphasized as an important adverse reaction in Denmark. However worldwide, several cases of hepatic injury have been reported. We report one case of Captopril-induced hepatic injury. Despite discontinuation of Captopril a hepatorenal syndrome developed and the patient died five weeks after admission. This report emphasizes the need to be aware of the possibility of hepatic injury in patients receiving Captopril.
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PMID:[Captopril-induced toxic hepatitis]. 141 40

We investigated the role of atrial natriuretic factor (ANF) and the renin-angiotensin system as well as the effects of losartan in rats with aortocaval (AC) shunts. Right atrial and left ventricular end-diastolic pressures (LVEDP) were higher and mean arterial blood pressure (MAP) was lower in AC shunt animals than in their controls. AC shunt rats presented marked cardiac hypertrophy, decreased right atrial ANF concentration, and increased ventricular ANF content and concentration. Plasma ANF levels were elevated, and hematocrit was lower in AC shunt animals than in controls. Captopril or losartan treatment decreased MAP and returned LVEDP to sham-operated control values. A clear regression of cardiac hypertrophy was evident in both treated AC shunt groups, with plasma ANF levels tending to follow those in sham-operated rats. Plasma COOH-terminal ANF levels were decreased and urinary volume and hematocrit were increased in losartan-treated AC shunt animals. We conclude that chronic angiotensin converting enzyme inhibition and angiotension II receptor antagonism improved hemodynamic conditions, diminished water retention, reversed cardiac hypertrophy, and restored plasma and tissue ANF to more "normal" levels in rats with moderate high-output heart failure.
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PMID:Chronic captopril and losartan (DuP 753) administration in rats with high-output heart failure. 141 10

1. Captopril was evaluated as an adjuvant to diuretic and digoxin therapy in heart failure in old age, using walking ability, minute ventilation and oxygen consumption and plasma atrial natriuretic factor (ANF) concentration as measures of outcome. 2. Twenty patients, mean (s.d.) age 81 (6) years, entered a double-blind, randomised, crossover study of three treatments, a twice daily regimen of captopril (AA), at a dosage established by titration against serum angiotensin converting enzyme (ACE) activity, the same dosage in the morning with placebo at night (AP), and twice daily placebo (PP). Each treatment lasted 3 weeks. A 2 week run-in period on triple therapy, with AA captopril, was used to assess stability and compliance. Seventeen completed all treatments: three completed two. 3. Any benefit of captopril was modest and there was deterioration in gait on the titrated dosage 3 months afterwards (P = 0.04). Efficacy in the old may be greatest when the titrated dose (25 or 50 mg) is given once daily: the multiple daily doses recommended may be unnecessarily demanding. 4. Walking performance was measured by gait analysis (GA) at free walking speed and by a simple walking test (SWT), in which patients stopped at the first relevant symptom. There was a consistent tendency for four measures of performance (GA: speed, stride length and double support time; SWT distance) to be best on the AP treatment, next best on AA, and worst on PP but for the fifth, SWT speed, AP and AA were similar. The trend appeared most marked for SWT distance, mean (s.e. mean) values for AP, AA and PP being 123 (15), 94 (16) and 75 (16) m, respectively. However, the treatment effect did not reach statistical significance at the 0.05 level. 5. There was no significant difference between treatments in minute ventilation, minute oxygen consumption, or their ratio, either at rest or on exercise. 6. Resting ANF concentrations were nearly four times higher (P = 0.0001) in the patients than those, mean (s.e. mean) 66 (5) pmol l-1, in eleven healthy volunteers of mean age 80 (6) years, and the increase on exercise, seen in the controls (P less than 0.01), was absent. In the patients the resting plasma ANF concentration was significantly affected by treatment (P = 0.03), being less on both AP, 245 (9), and AA, 214 (9) than on PP, 264 (10) pmol l-1 (P = 0.02 and 0.03, respectively). 7. Baseline serum ACE activity was induced on active treatment. The change in ACE activity at 3 h post an active dose was significantly greater on AP than AA (P = 0.005). The increased sensitivity to inhibition during once daily administration was reflected in mean arterial pressure. The pre-dose standing pressure was less on AP than on PP (P less than 0.05), and the change in postural fall (pre-dose minus 2 h post), was greater (P = 0.004), but AA and PP were similar in these respects.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effect of captopril on functional, physiological and biochemical outcome criteria in aged heart failure patients. 153 21

Acute hemodynamics of pimobendan were compared to captopril in a crossover trial in patients with chronic heart failure (NYHA II-III). Heart failure had been stabilized by conventional therapy with diuretics and digitalis for more than 2 weeks. Patients receiving vasodilators were excluded. The hemodynamics were analyzed using a Swan-Ganz catheter at the bedside during drug administration. Following an intravenous injection of 2.5 mg of pimobendan, there was a significant increase in heart rate and decrease in mean pulmonary artery pressure, total pulmonary resistance, mean arterial pressure, systemic vascular resistance and mean right atrial pressure 2 hours after the injection. Captopril (12.5 mg, orally) significantly decreased mean arterial pressure, systemic vascular resistance and double product 2 hours after administration. In this study, the inotropic effect was evaluated through the relation between the stroke volume index and diastolic pulmonary artery pressure, and also between the stroke volume index and mean arterial pressure. Although decreases of diastolic pulmonary artery pressure and mean arterial pressure were seen with both drugs, the differences in stroke volume index were not significant. In comparison with captopril, the acute hemodynamics of pimobendan are characterized as follows: 1) the systemic arteriovasodilating effects of the two drugs were equal, 2) the pulmonary arteriovasodilating effect of pimobendan was marked, 3) a venodilating effect, documented through a decrease of mean right atrial pressure, was seen only with pimobendan. This study concluded that pimobendan is a stronger arterio-venodilator than captopril.
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PMID:Acute hemodynamics of pimobendan in chronic heart failure. A comparative crossover study of captopril and pimobendan. 159 49

The left ventricle progressively dilates in some patients after acute myocardial infarction (AMI). Both systolic and diastolic left ventricular (LV) dysfunction can be of significance in the development of heart failure. Captopril has been shown to prevent dilatation, but the effect on LV diastolic function is unknown. In a placebo-controlled double-blind parallel study, 58 AMI patients with heart failure or low ejection fraction, or both, were consecutively randomized at day 7 to either placebo or captopril (25 mg twice daily). No differences were present between the groups at baseline. Fifty-three patients completed the 6-month study period. Both LV diastolic and systolic volume indexes increased significantly in the placebo group (17 and 14%, respectively); in the captopril group there was no change in LV diastolic volume index, but a 13% reduction in LV systolic volume index. Ejection fraction increased significantly in the captopril group. The peak flow velocities of the early and atrial filling phases were measured, and the ratio between the velocities was calculated. A significant reduction was observed during the study period in early peak flow velocity (65 to 52 cm/s) and in the ratio between early and atrial peak flow velocity (1.3 to 0.8) in the placebo group (p less than 0.05), but no significant changes occurred in the captopril group. No correlation was found between dilatation of the left ventricle and reduction in early peak flow velocity or the ratio between early and atrial peak flow velocity. In conclusion, captopril prevented LV dilatation, improved ejection fraction and prevented LV diastolic dysfunction in AMI patients with early signs of LV systolic dysfunction.
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PMID:Effects of captopril on left ventricular systolic and diastolic function after acute myocardial infarction. 162

Ten healthy (aged 28 to 39) and ten heart failure NYHA II (aged 19 to 49) male subjects were prospectively studied under no drugs, under furosemide (40 mg/day), under captopril (150 mg/day) and under their association. Arterial compliance (ml/mmHg) was measured in all subjects at rest and supine. Heart failure etiology was dilated cardiomyopathy or ischemic heart disease without significant regurgitation. Arterial compliance was significantly higher in healthy than in heart failure patients in all studied conditions (p less than 0.001) (healthy = 2.2 + 0.29 vs. heart failure = 0.79 + 0.14). Neither single drug nor their association induced any change in healthy subjects. Arterial compliance progressively increased in heart failure with furosemide, captopril, and their association (no drug = 0.79 + 0.14; furosemide = 0.87 + 0.15; captopril = 0.94 + 0.15 and furosemide + captopril = 0.99 + 0.14). Captopril induced a higher increment than furosemide (p less than 0.001) and their association even a higher increment (p less than 0.001) than any single drug. Thus captopril and/or furosemide increased arterial compliance in heart failure but not in healthy subjects, possibly through changes in arterial wall edema and smooth muscle contraction.
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PMID:Effect of drugs on a noninvasive index of arterial compliance in healthy and heart failure patients. 174 91

After large myocardial infarction, compromised left ventricular (LV) function and changes in the peripheral circulation result in the syndrome of chronic congestive heart failure. Although treatment with angiotensin-converting enzyme inhibitors improve cardiovascular function, it is difficult to determine whether this benefit is due to changes in organ versus muscle function. The rat model of heart failure, created by ligating the left coronary artery, results in pathophysiology that is similar to that seen in patients, i.e., increased LV end-diastolic pressure and volume, hypertrophy of the noninfarcted myocardium, prolongation of the time constant of LV relaxation, decreased venous compliance, and increased total blood volume. In noninfarcted papillary muscles, isolated from rats with heart failure, maximal developed tension and peak rate of tension rise (+dT/dt) are decreased, time to peak tension is prolonged, and myocardial stiffness is increased. Morphologic changes include an increase in papillary muscle myocyte cross-sectional area and an increase in myocardial hydroxyproline content. Captopril (2 g/liter drinking water) alters LV loading by decreasing arterial pressure, increasing venous compliance, and decreasing blood volume. This results in a decrease in LV end-diastolic pressure and volume. In the noninfarcted myocardium, time to peak tension is shortened, whereas developed tension, +dT/dt, and muscle stiffness remain abnormal. Captopril decreases myocyte cross-sectional area, but collagen content remains elevated. Thus, in the rat infarct model of heart failure, treatment with captopril alters LV remodeling and hypertrophy but produces only modest improvement in muscle function.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of captopril on contractility after myocardial infarction: experimental observations. 174 17

In 33 patients with heart failure (NYHA II-III), the 24-h blood pressure rhythm was examined before and after the titration period of two ACE inhibitors. Blood pressure was measured by the oscillometric method using the blood pressure monitor 90202 from SpaceLabs, Inc. The measurements were taken from 06:00 to 22:00 h every 20 min and from 22:00 to 06:00 h every hour. Patients were randomized to therapy with either captopril (group 1, n = 17) or enalapril (group 2, n = 16). The average daily dosage of captopril was 41 +/- 3 mg given in three divided doses (08:00, 12:00, and 17:00 h). The mean dose of enalapril was 8 +/- 1 mg once daily (08:00 h). Serum electrolytes, serum creatinine, and plasma renin activity were measured before and during therapy with both ACE inhibitors. Twenty-four-hour blood pressure measurements were taken before and on the fifth day of treatment with ACE inhibitors. Both groups were not different with respect to the degree of heart failure, the concomitant medication, and the 24-h profiles of blood pressure and heart rate before initiation of ACE inhibition. The 24-h blood pressure values on day 5 were consistently below the pretreatment values (p less than 0.005) in both groups. Both groups did not differ significantly during ACE inhibition in their 24-h blood pressure and heart rate profiles. In both groups, the mesor of the systolic and diastolic blood pressure decreased significantly by the same degree (by 4.7/5.1 mmg Hg in group 1 and 6.4/4.1 mm Hg in group 2). The systolic/diastolic blood pressure amplitude decreased slightly in both groups. Before treatment, serum sodium, potassium, and creatinine were within the normal range. The increase in potassium (0.5 +/- 0.1 mmol/L) reached statistical significance (p less than 0.01) only in the captopril group, whereas it was not significant in the enalapril group (0.1 +/- 0.1 mmol/L). Serum creatinine was not significantly altered by both ACE inhibitors. No relationship could be found between the changes in serum potassium or creatinine and the mean of the 24-h blood pressure values during ACE inhibition. Captopril and enalapril showed comparable blood pressure profiles and similar effects on renal function at the end of the titration on day 5. It can therefore be concluded that the effects on blood pressure rhythm and renal function are similar with a single daily dose of enalapril compared to captopril given three times daily.
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PMID:Circadian rhythm of blood pressure in congestive heart failure and effects of ACE inhibitors. 181 90

Progression of heart failure ("expected mortality") and sudden cardiac death ("unexpected mortality"), presumably secondary to ventricular arrhythmia, are the major causes for the poor prognosis in chronic heart failure (CHF). Limitations of this classification ultimately stem from inaccuracies in establishing the mechanism of death at the time of death. Elucidation of the determinants of patients prone to sudden death and the effects of treatment modalities on the rate of sudden death remain hidden. Unexpected mortality is probably secondary to arrhythmic death but denotes only that death occurred within some brief interval (arbitrarily less than one hour in most studies) and does not exclude other causes. The demonstrated benefit of ACE inhibitors for improving total mortality as illustrated by the findings of the VHeFT, Captopril Multicenter and CONSENSUS, and the improved event-free survival shown by Munich Mild Heart Failure Trial for low-dose captopril argues strongly for their use in patients with CHF. These agents are confirmed to reduce the risk of death from pump failure; the effects on sudden death are less clear. Although many favorable effects contribute to improved hemodynamics, neuroendocrine and electrolyte status as discussed, at present, it is not possible to predict the precise mechanism by which these agents extend life and whether they reduce the frequency of "sudden" deaths.
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PMID:Can angiotensin converting enzyme (ACE) inhibitors influence the risk of sudden cardiac death in patients with heart failure? 182 Feb 99

Angiotensin I converting enzyme (ACE) inhibitors are widely used in the treatment of heart failure. It is not known whether the beneficial effects of ACE inhibition are only due to a reduction in pre- and afterload or whether ACE inhibition also has direct effects on cardiac remodeling processes after myocardial infarction. In addition, the effects of differential timing of the treatment are not known. The left coronary artery was ligated in rats to induce a myocardial infarction. Control rats received no treatment. Captopril was given via s.c. placed minipumps (500 micrograms/kg.h) in the first 3 weeks or in the third and fourth week after induction of the myocardial infarction. The structural changes of the heart were investigated. Early after ligation the left ventricle was dilated in association with a marked, but transient DNA synthesis in the remaining left ventricle; the amount of collagen also increased. Early captopril treatment blocked this response, while late treatment had no effects. We suggest that the negative effects of early captopril treatment are due to an interference with the normal adaptive responses of the heart to the loss of muscle, probably through interactions at the cellular level.
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PMID:Angiotensin I converting enzyme inhibitors and cardiac remodeling. 182 81


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