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

The non-sulfhydryl selective angiotensin-converting enzyme inhibitor benazepril (20 mg daily) was compared with hydrochlorothiazide (50 mg daily) in post-infarction (6-24 months) patients with symptomatic (NYHA functional class 2) mild heart failure. No concomitant drug therapy was given. The study had a double-blind cross-over design with 3-month treatment periods. Both drugs were well tolerated, and both caused a similar reduction in systolic blood pressure. Heart rate was higher with the diuretic. Benazepril improved the NYHA functional class in 17 out of 29 (59%) patients, whereas one patient improved with hydrochlorothiazide (P = 0.0004). With regard to global efficacy score, benazepril was also superior. Thus, angiotensin-converting enzyme inhibitors may be superior to diuretics as first-choice therapy in symptomatic mild heart failure.
 ...
PMID:A 3-month double-blind cross-over study of the effect of benazepril and hydrochlorothiazide on functional class in symptomatic mild heart failure. 161 82

We studied 14 patients who had exercise-induced ventricular arrhythmias after a previous Q-wave myocardial infarction. All had symptomatic mild heart failure in New York Heart Association class II and a maximal oxygen consumption between 16 and 20 ml/kg/min. They were treated with the angiotensin converting enzyme inhibitor benazepril (20 mg) and hydrochlorothiazide (50 mg) for 3 months in a double-blind randomized cross-over study. Benazepril improved the maximal oxygen uptake by 15% and exercise time by 18%. Hydrochlorothiazide slightly increased exercise time (5%) and the respiratory exchange ratio but not oxygen consumption. The arrhythmias were nonsustained and reproducible in two baseline recordings. Compared with baseline, benazepril reduced the mean number (3.5 +/- 2.5) (+/- SD) of episodes of ventricular tachycardia by 66%, and total (47.4 +/- 40.9) and paired (5.2 +/- 4.5) premature ventricular contractions by 61% and 62%, respectively. Hydrochlorothiazide did not reduce the number of arrhythmias. Thus an improved cardiac function induced by benazepril is associated with a reduction in exercise-induced ventricular arrhythmias in patients with symptomatic mild heart failure after infarction.
 ...
PMID:Reduction of exercise-induced ventricular arrhythmias in mild symptomatic heart failure by benazepril. 767 69

The purpose of this study was to examine the sequential changes in renal and cardiovascular function produced by chronic Benazepril administration at different stages of heart failure in dogs. Heart failure was produced by rapid ventricular pacing in five dogs with a normally functioning renin-angiotensin system (angiotensin normal, AN) and six dogs chronically administered the angiotensin-converting-enzyme inhibitor (ACEI) Benazepril. After 7 days of pacing, cardiac output was significantly higher and total peripheral resistance (TPR) lower in the ACEI compared with the AN dogs. Cumulative sodium and water balance increased significantly in both groups, but after 7 days of pacing there were no significant differences between groups. However, the rate of increase in sodium and water balance was significantly less in the ACEI group. Effective renal plasma flow decreased in the AN and ACEI groups during pacing, but there were no between-group differences, and no significant changes in glomerular filtration rate (GFR) occurred in either group. In the AN dogs, pacing was continued for 7-21 days until the onset of decompensated heart failure. Urinary sodium excretion increased on the first day of ACEI infusion during this stage but returned to pre-ACEI levels during the next 2-3 days. No significant improvement in cardiac output was measured during ACEI in decompensated heart failure. These data suggest that chronic ACEI administration can improve renal and cardiac function in early heart failure without impairing GFR but is less chronic ACEI administration can improve renal and cardiac function in early heart failure without impairing GFR but is less effective in later, decompensated stages.
 ...
PMID:Chronic angiotensin-converting-enzyme inhibition improves cardiac output and fluid balance during heart failure. 844 98

Benazepril (BP), an angiotensin convertive enzyme inhibitor, was administered orally once daily for 4 weeks to 31 dogs with mild to moderate (NYHA functional classes II and III) congestive heart failure caused from mitral insufficiency (MI). There were no significant changes in clinical signs, electrocardiogram findings, radiographical observations and plasma biochemical results in 11 dogs treated with placebo for 4 weeks. In 31 dogs treated with BP, appetite increased, and mean scores of heart failure signs, such as activity, exercise tolerance, cough and respiratory effort, were significantly improved. No dog displays signs suggesting systemic hypotension. One dog died suddenly on the 26th day of treatment with BP. This dog had good vigor and appetite till the evening before the death, and cough and exercise tolerance had been gradually improving. The heart rate and ECG parameters of BP treated dogs did not change significantly, but length of long axis of the heart decreased. In plasma biochemical tests, plasma urea nitrogen (UN) levels did not change significantly, and plasma creatinine (CRE) levels increased slightly within the normal ranges during BP trial. Two dogs had higher plasma UN levels with slightly higher plasma CRE levels, but had normal general condition and other biochemical results. Plasma ACE activity decreased to 57.3% of pre-treatment level at 4 weeks after BP treatment. It is concluded that BP monotherapy was efficacious at least in dogs with relatively low grade congestive heart failure caused by MI.
 ...
PMID:Efficacy of monotherapy with benazepril, an angiotensin converting enzyme inhibitor, in dogs with naturally acquired chronic mitral insufficiency. 927 44

Mortality remains high in chronic heart failure (CHF) because under ACE inhibitor treatment other neurohumoral systems remain/become (de)activated, such as the endothelin and atrial natriuretic peptide pathways. Dual endothelin-converting enzyme-neutral endopeptidase (ECE-NEP) inhibition exerts beneficial effects in experimental CHF, but whether "triple" ACE-ECE-NEP inhibition is superior to ACE or ECE-NEP inhibition is unknown. We compared, in rats with CHF, ACE-ECE-NEP to ACE or ECE-NEP inhibition in terms of left ventricular (LV) hemodynamics and remodeling. Benazepril (2 mg/kg/d) or the ECE-NEP inhibitor CGS26303 (10 mg/kg/d) were administered alone or in combination (subcutaneously for 28 days starting 7 days after coronary ligation). ACE-ECE-NEP inhibition reduced blood pressure more markedly than ACE or ECE-NEP inhibition. All treatments increased cardiac output to the same extent, but ACE-ECE-NEP inhibition reduced LV diameter and LV end-diastolic pressure more markedly than ACE or ECE-NEP inhibition. The reduction of LV weight and collagen accumulation in the "viable" myocardium was most pronounced after ACE-ECE-NEP inhibition. These results, obtained in experimental CHF, illustrate a further improvement of LV hemodynamics and structure after ACE-ECE-NEP inhibition compared with either ACE or ECE-NEP inhibition, but whether this is associated with a further improvement of exercise tolerance and/or survival remains to be determined.
 ...
PMID:Triple ACE-ECE-NEP inhibition in heart failure: a comparison with ACE and dual ECE-NEP inhibition. 1611 47

Angiotensin-converting enzyme (ACE) inhibitors represent one of the most commonly used categories of drugs in canine and feline medicine. ACE inhibitors currently approved for use in veterinary medicine are benazepril, enalapril, imidapril and ramipril. They are all pro-drugs administered by oral route. A physiologically based model taking into account the saturable binding to ACE has been developed for pharmacokinetic analysis. The bioavailability of the active compounds from their respective pro-drug is low. The active metabolites are eliminated by renal, hepatorenal or biliary excretion, according to the drug. The elimination half-life of the free fraction of the active compounds is very short (ranging from approximately 10 min to 2 h). ACE inhibitors are generally well tolerated. Benazepril, enalapril, imidapril and ramipril are approved for dogs with chronic heart failure (CHF). The efficacy of ACE inhibitors has been convincingly demonstrated in dogs with CHF, especially in those with chronic valvular disease. In such clinical settings, ACE inhibitors improve hemodynamics and clinical signs, and increase survival time. In cats with cardiovascular disease, little information is available except for reports of some benefit in cats with hypertrophic cardiomyopathy in two non-controlled investigations. ACE inhibitors have also a mild to moderate hypotensive effect. There is also evidence to recommend ACE inhibitors in dogs and cats with chronic renal failure (CRF). They decrease the glomerular capillary pressure, have antiproteinuric effects, tend to delay the progression of CRF and to limit the extent of renal lesions.
 ...
PMID:Angiotensin-converting enzyme inhibitors in veterinary medicine. 1750 20