Peripheral hemodynamic effects of captopril in patients with congestive heart failure

In 14 patients with severe congestive heart failure, the effects of captopril on the forearm circulation were evaluated with strain gauge plethysmography. Changes in plasma renin activity, angiotensin II, norepinephrine, epinephrine, bradykinin, prostaglandin E2, and 6-keto-prostaglandin F1 alpha concentrations were also measured. To determine whether the prostaglandins contribute to the peripheral hemodynamic response to captopril, the hemodynamic and hormonal measurements were repeated after pretreatment with indomethacin, an inhibitor of prostaglandin synthesis. Ninety minutes after administering a single dose of captopril (25 mg), mean blood pressure and venous pressure decreased (p less than 0.01 and p less than 0.05, respectively), forearm blood flow and maximum venous volume increased (p less than 0.05 for both), and forearm vascular resistance and forearm venous tone decreased (p less than 0.05 for both). Captopril also improved forearm venous distensibility (p less than 0.05). Pretreatment with oral indomethacin (50 mg) significantly blunted all of these captopril-induced hemodynamic changes. The blockage of the renin-angiotensin system by captopril was unaltered by indomethacin pretreatment. Captopril significantly increased plasma bradykinin, prostaglandin E2, and 6-keto-prostaglandin F1 alpha (p less than 0.05 for each). Indomethacin pretreatment did not affect the captopril-induced increase in bradykinin, but it did completely eliminate the increase in the prostaglandins. Plasma catecholamines did not change with captopril. These data suggest that the vasodilator prostaglandins play a significant role in captopril's peripheral vasodilative effects in congestive heart failure.     

Hemodynamic effects of digoxin on congestive heart failure

To assess the hemodynamic effects of digoxin (0.01 mg/kg) on congestive heart failure, we evaluated 19 patients with decreased contraction force of left ventricle (old myocardial infarction n = 9, and dilated cardiomyopathy n = 10, group 1) and 8 patients with mechanical impaired left ventricular filing (mitral stenosis n = 8, group 2). In groups 1 and 2, heart rate and pulmonary capillary pressure significantly decreased (p less than 0.05). In group 1, stroke volume increased, but not significantly. In group 2, stroke volume increased significantly (p less than 0.05). There were no significant changes in blood pressure and systemic vascular resistance in either group. We divided group 1 into two groups (group 1A: cardiac index increased more than 15%, group 1B: cardiac index increased less than 15%). In group 1A, cardiac index and % fractional shortening before digoxin administration were lower than in group 1B (1.97 + 0.27 vs 2.80 + 0.481/min/m2, p less than 0.001, and 10.9 + 8.0 vs. 19.5 +11.9%, p less than 0.05, respectively). These data suggested that digoxin exerted a positive inotropic effect with decreased pulmonary capillary pressure but cardiac index did not always increase in congestive heart failure.     

Haemodynamic effects of dobutamine in patients with congestive heart failure receiving captopril.

Treatment with captopril has proved effective in some patients with resistant heart failure. Since cardiac output responses to captopril treatment are generally small, we infused the positive inotropic agent dobutamine in six patients already receiving captopril to determine whether cardiac output could be augmented without concomitantly increasing myocardial oxygen demands. At low infusion rates of dobutamine (2.5 and 5 microgram/kg per min), a substantial rise in cardiac output was observed yet myocardial oxygen uptake remained well below baseline (pre-captopril/dobutamine) levels. At higher rates of infusion (10 and 20 microgram/kg per min) the rise in cardiac output was accompanied by a pronounced increase in myocardial oxygen uptake, and the appearance of chest pain or multifocal ventricular extrasystoles in three patients. These data indicate that captopril treatment combined with low infusion rates of dobutamine can augment cardiac output in the short term, without increasing myocardial oxygen demand.     

Hemodynamic and clinical effects of captopril in congestive heart failure

The acute and chronic effects of Captopril were evaluated in 8 patients (5 males and 3 females, age 49 +/- 17 years) with chronic severe congestive heart failure. Acute hemodynamic effects were studied according to a randomized, double blind, placebo controlled protocol, by using two doses of Captopril (25 and 50 mg). The usual diuretic and digitalis treatment was kept unchanged throughout the trial. The acute administration of placebo associate with the usual doses of diuretic and digitalis was followed after 2 hours by a significant reduction of mean pulmonary wedge pressure (-23%, p less than 0.05). One hour following a single administration of Captopril, the following significant (p less than 0.05) changes were observed, respectively for the doses of 25 and 50 mg: heart rate -9% and -6%, cardiac index +13% and +10%, mean pulmonary wedge pressure -27% and -35%, mean pulmonary arterial pressure -29% and -26%, systemic vascular resistances -20% and -17%. A longer duration of effects on heart rate and cardiac index was noted after the 50 mg dose. All patients received long-term treatment with Captopril 75 or 150 mg daily. The NYHA functional class improved in all cases and there was a significant decrease of the cardio-thoracic ratio (from 0.61 +/- 0.05 to 0.55 +/- 0.09, p less than 0.01). A repeated hemodynamic study after a mean period of 6.5 months (range 2.5-22 months) revealed in 7 cases a sustained effect of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of captopril on congestive heart failure

1) Captopril was orally administered in a dose of 12.5 mg to 12 patients with congestive heart failure to follow changes in its blood concentration and determine changes in clinical test values. 2) The blood concentration of captopril reached its peak in 2 h after medication, the mean value being 274 ng/ml and the half-life 3.16 h. The Tmax and T1/2 were found to be extended as compared with those of normal humans and hypertensive patients that had been reported. No significant differences were noted between Group I of mild cases and Group II of serious cases. 3) Following administration of captopril, a rise in angiotensin I and renin activity and a reduction in aldosterone were noted. These were found to be correlated or inversely correlated with the changes in the blood concentration of captopril. Greater changes were noted in Group II than in Group I. All clinical test values in each group tended to return to the control value 6h after the administration.     

Coronary hemodynamic effects of angiotensin inhibition by captopril and teprotide in patients with congestive heart failure

The coronary hemodynamic effects of vasodilator therapy with angiotensin-converting enzyme inhibitors (captopril arid teprotide) were studied in 11 patients with ischemic heart disease and severe congestive heart failure (CHF). Over 2 hours, systemic vascular resistance was reduced from 2,408 ± 240 to 1,715 ± 170 dynes·s·cm^?5 (p < 0.001), and cardiac output improved 18%, resulting in lower arterial pressure (101 ± 8 to 86 ± 5 mm Hg, p < 0.001) and left ventricular filling pressure (30 ± 2 to 21 ± 2 mm Hg, p < 0.001). Coronary sinus thermodilution blood flow parallelled perfusion pressure but did not significantly vary overall (160 ± 20 to 133 ± 12 ml/min, difference not significant [NS]). Coronary vascular resistance was unchanged. Although the left ventricular stroke work index rose slightly (37.7 ± 8.8 to 41.3 ± 7.9 g·m/m², p < 0.05), there was no change in the coronary arteriovenous oxygen content difference (10.8 ± 1.0 to 10.4 ± 1.0 ml/100 ml, NS) or calculated myocardial oxygen consumption (16.4 ±1.9 to 13.9 ± 1.6 ml/min, NS). The heart rate-systolic blood pressure product declined significantly during this period (8,824 ± 703 to 7,087 ± 514 beats·mm Hg, p < 0.02); this relief of cardiac effort was a function of the pretreatment plasma renin activity. A derived index of external myocardial efficiency improved 37% (19 ± 3 to 26 ± 6, p < 0.05), reflecting greater left ventricular work without increased oxygen demand.Enhancement of myocardial performance after converting enzyme inhibition appears dependent on reduction of angiotensin-mediated ventricular afterload and preload. The lack of coronary vasomotor effects in patients with advanced ischemic cardiomyopathy may reflect limited coronary vascular reserve. Improvement of heart failure in these patients developed without evidence of myocardial ischemia, since balance was maintained between oxygen supply and demand.     

Hemodynamic effects of intravenous prenalterol in patients on long-term digoxin therapy for congestive heart failure

The hemodynamic effects of a new beta-1-adrenoceptor agonist,prenalterol, were studied in 12 patients with regurgitant valvedisease and/or ischemic heart disease (prenalterol group). Fiveother patients were randomized to a control group and studiedin the same way except that saline was administered insteadof prenalterol. All patients were on long-term digoxin therapy.Heart rate, stroke volume, cardiac output, arteriovenous oxygendifference, pressures in the right atrium, pulmonary arteryand left ventricle were determined both at rest and during recumbentexercise before and after administration of 50 µg prenalterol/kgbody weight, or of saline. Prenalterol caused a significant increase in heart rate andcardiac output and a significant reduction in arteriovenousoxygen difference, in left ventricular filling pressure andin right atrial pressure both at rest and during exercise. Asignificant increase of stroke volume was seen only during exercise.In the placebo group, no significant hemodynamic changes wererecorded. No adverse effects were observed. Thus, prenalterol seems to have beneficial hemodynamic effects,additive to those of digitalis. The drug is potentially usefulin the treatment of heart failure, but further studies on thespecific mechanism of action and the long-term effects are warranted.     

Long-term control of congestive heart failure with captopril

The long-term effects of captopril therapy were assessed by sequential hemodynamic studies over a 6 month period in 19 patients with resistant congestive heart failure. Initial improvement during the first week of therapy was noted only in 11 and was marked by significant (p < 0.005) increases in cardiac output and stroke volume, slowing of heart rate, and reduction of total peripheral resistance. Of the remaining eight patients, seven improved subsequently with maintained therapy so that by the end of 3 months of treatment only one patient failed to respond significantly.The hemodynamic index that reflected response most consistently was the shortening in pulmonary mean transit time. Simultaneously with clinical improvement there was a reduction in cardiopulmonary volume that reflected a reduction in pulmonary congestion and probably systemic venodilation. Associated with these hemodynamic changes there was an increase in plasma renin activity and a significant reduction in plasma aldosterone, but these changes did not differ significantly between patients who responded markedly and those who responded moderately to converting enzyme inhibition.These results suggest that the response of congestive heart failure to captopril can occur gradually. Improvement was related to peripheral hemodynamic changes which led to a reduction in both total peripheral resistance and cardiopulmonary volume. The reduction in the plasma aldosterone/renin activity ratio was an effective marker of compliance.     

Acute and chronic effects of ramipril and captopril in congestive heart failure

We studied the acute and long-term effects of ramipril and captopril in 12 patients with moderate to severe congestive heart failure using an open, parallel design. Drug doses were titrated. Compared with baseline values, maximal haemodynamic and humoral effects after the first dose of both angiotensin converting enzyme inhibitors were similar, but the effects of ramipril (5 mg) demonstrated a slower onset of action and a significantly longer duration than captopril (12.5 mg). After 3 months of treatment a single dose of 5 mg ramipril showed the same 24-hour haemodynamic profile as after the first dose, but the hypotensive effect was less marked. There was no plasma accumulation of ramiprilat. Serum creatinine and potassium remained stable, except for one patient whose renal function deteriorated on captopril treatment. Complex ventricular arrhythmias occurred in 11 patients and were unaffected after treatment with ramipril or captopril. Two patients died suddenly during ramipril therapy and one patient during captopril therapy. In summary, ramipril is an effective, long-acting angiotensin converting enzyme inhibitor, producing long-term haemodynamic effects in patients with congestive heart failure. Using an individualised dosage scheme, neither long-lasting hypotension nor deterioration of renal function occurred. No effect on ventricular arrhythmias was seen.     

Comparative effects of long-term therapy with captopril and ibopamine in chronic congestive heart failure in old patients

Little is known concerning the long-term drug management of chronic heart failure (CHF) in old patients (greater than or equal to 75 years). Accordingly, this double-blind, placebo-controlled trial compared the long-term (over 6 months) effect of captopril (37.5-75 mg/day) and of ibopamine (150-300 mg/day) on exercise testing, symptoms and subjective feeling of well-being, in 150 CHF elderly patients (mean age 75 years) under treatment with digitalis and/or diuretics. During an additional open follow-up of approximately 1.5 years, morbid events and deaths were also recorded. Captopril and ibopamine performed better (p less than 0.01) than placebo, improving the 6-min walking distance (captopril from 300 to 404 m, ibopamine from 282 to 385 m; placebo from 283 to 299 m). NYHA status, symptom score and patients' global assessment. The difference between the active study drugs was not statistically significant (p greater than 0.05). Complicating events, including diuretic use, frequency of hospitalization, worsening of CHF and deaths, were grouped by patient-years. These events were significantly (p less than 0.01) lower (captopril: 28/75 patient-years; ibopamine 33/74 patient-years) in the active treatment groups with respect to placebo (58/96 patient-years). Captopril and ibopamine showed a different safety profile. Creatinine increase (2 patients), symptomatic hypotension (4 patients), hyperkalemia (2 patients) and upper respiratory symptoms were mostly associated with captopril treatment. Gastrointestinal adverse events were observed in 11 patients under ibopamine treatment. The study provides evidence of the clinical usefulness of both captopril or ibopamine in the long-term treatment of CHF in old patients. The safety profile of each drug will suggest the preferred therapeutic application.     

Effect of captopril on the exercise performance in patients with congestive heart failure]

We studied the effect of captopril on exercise performance in 30 patients with congestive heart failure using a randomized, double-blind and placebo-controlled method. 4-week captopril treatment can significantly increase the exercise tolerance time and work load, heart function, blood flow in exercising lower limbs as well as oxygen metabolic capacity. However, 3-day captopril treatment had no effect on exercise performance. A significant correlation was found between improvement in exercise performance and the pretreatment level of plasma angiotensin II. The increased levels of plasma prostaglandins E 2 and I 2 after captopril treatment were also correlated with improvement of exercise performance. The results indicated that long-term captopril treatment can increase exercise performance in congestive heart failure by improving both central and peripheral hemodynamics and metabolism. Certain vasomotor or endocrine factor may play a mediate role in the above changes.     

The effect of bunazosin vs captopril on hemodynamic and neurohumoral parameters in patients with congestive heart failure

The hemodynamic parameters (right atrial pressure, mean pulmonary artery pressure, pulmonary capillary wedge pressure, cardiac index, heart rate, blood pressure) and neurohumoral responses (alpha-ANP, plasma renin activity, aldosterone, angiotensin II) of Captopril, oral ACE inhibitor, and Bunazosin, oral alpha 1-blocker, were investigated in 28 patients with congestive heart failure at rest and after exercise. These data were analysed in both acute and chronic phases. 1) Acute effect. Captopril produced significant improvement of neurohumoral factors at rest and also after exercise. Bunazosin reduced alpha-ANP, but other neurohumoral factors did not change. Bunazosin produced significant hemodynamic improvement both at rest and after exercise. 2) Chronic effect. Captopril produced significant hemodynamic improvement both at rest and after exercise. Improvement of neurohumoral factors in acute phase was also preserved at chronic phase. On Bunazosin, improvement of hemodynamics at acute phase was also preserved at chronic phase without deterioration of neurohumoral factors.     

Comparative hemodynamic and neurohormonal effects of intravenous captopril and digoxin and their combinations in patients with severe heart failure

The effects of intravenous captopril and intravenous digoxin given separately and in combination on rest and exercise hemodynamics were studied in 16 patients with severe heart failure and sinus rhythm. When given separately, both captopril and digoxin decreased the pulmonary capillary wedge pressure by, respectively, 24% (p = 0.003) and 34% (p = 0.004) and systemic vascular resistance by 23% (p = 0.09) and 20% (p = 0.03). Only digoxin increased cardiac index by 23% (p = 0.03) and stroke work index by 52% (p = 0.01). During maximal exercise, captopril alone decreased systemic vascular resistance by 28% (p = 0.0002) and increased cardiac index by 33% (p = 0.02). Digoxin alone decreased pulmonary capillary wedge pressure by 11% (p = 0.04) and increased stroke work index by 44% (p = 0.01). The combination of captopril and digoxin resulted in a decrease in pulmonary capillary wedge pressure and systemic vascular resistance and an increase in cardiac index and stroke work index both at rest and during exercise that was greater than values observed with either drug given alone. Cardiac index response to the combination of captopril and digoxin correlated with baseline serum aldosterone concentration (r = 0.81, p less than 0.001) and plasma renin activity (r = 0.74, p less than 0.0002). A significant decrease in norepinephrine concentration was noted after digoxin was administered alone or added to captopril. These findings demonstrate that in patients with severe heart failure, the acute administration of captopril and digoxin has an independent salutary hemodynamic effect. The combination of these agents, however, has an adjunctive effect on cardiac function at rest and during exercise.     

Sublingual administration of captopril versus nitroglycerin in patients with severe congestive heart failure

Angiotensin-converting enzyme inhibition has proven to be a successful approach for the long-term treatment of patients with congestive heart failure. This investigation compared the acute hemodynamic changes after sublingual administration of the angiotensin-converting enzyme inhibitor captopril with those after nitroglycerin. A total of 24 patients with severe left heart failure (New York Heart Association classes III and IV) were given 25 mg captopril and 0.8 mg nitroglycerin sublingually in this randomized, cross-over study. Hemodynamic monitoring revealed a clear improvement in pre- and afterload parameters for both drugs (P less than 0.01 and P less than 0.001), while captopril induced a higher increase in cardiac index (+49.2% vs. +25%), stroke volume index (+53.5% vs. +25.7%), and stroke work index (+55% vs. +28%) than nitroglycerin (P less than 0.001). Although not statistically significant, the onset of change for most hemodynamic parameters was measured earlier after nitroglycerin (after 12-19 vs. 16-22 minutes). Captopril revealed later peak effects (after 47-84 vs. 25-55 minutes, P less than 0.001) and a longer sustained improvement in hemodynamic values (return to baseline values after 117-162 vs. 68-120 minutes, P less than 0.001). No side effects occurred after either captopril or nitroglycerin in this study. Thus, these results indicate there is an early improvement in hemodynamic parameters after the sublingual administration of both drugs in patients with severe congestive heart failure, and that captopril induces a more pronounced and prolonged improvement than nitroglycerin.