EFFECTS OF CAPTOPRIL ON ABNORMALITIES OF THE PERIPHERAL CIRCULATION AND RESPIRATORY FUNCTION IN PATIENTS WITH SEVERE HEART FAILURE

doi:10.1016/S0140-6736(84)91557-5

The Lancet

Volume 324, Issue 8412, 17 November 1984, Pages 1120-1124

https://doi.org/10.1016/S0140-6736(84)91557-5 Get rights and content

Abstract

Limb blood flow and respiratory function were compared in ten patients with severe heart failure inadequately controlled by diuretics and normal control subjects matched for age and sex. Both forearm and calf blood flow, at rest and after exercise, were lower in the patients than in the control subjects. Oxygen consumption during submaximal exercise was also lower in the patients and minute ventilation was higher. Captopril, administered in a single-blind controlled study to the patients, resulted in an improvement in these abnormalities, with the exception of oxygen consumption. It also improved exercise tolerance and reduced perceived exertion during exercise. Captopril is

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Cited by (17)

Effects of exercise training on limb blood flow in patients with reduced ventricular function
1998, American Heart Journal
Background Among the factors that contribute to limiting exercise tolerance in chronic heart failure are reduced peripheral blood flow and impaired vasodilatory capacity. Exercise training improves vasodilatory capacity in normal subjects, but controlled studies of exercise training evaluating upper and lower limb blood flow rates have not been performed in patients with reduced ventricular function. Improved vasodilatory capacity could help explain how training increases exercise capacity in these patients.
Methods Twenty patients (mean age 55 ± 6 years) with reduced left ventricular function (mean ejection fraction 32% ± 6%) after a myocardial infarction were randomized to a 2-month high-intensity residential rehabilitation program or to a control group and were monitored over the subsequent year. Both groups were treated according to current practice with angiotensin-converting enzyme inhibition therapy. Training began 1 month after myocardial infarction. Baseline and postischemic flow rates were measured by plethysmography in both the upper and lower limbs 1 month, 3 months, and 1 year after the infarction. Peak oxygen uptake (Vo₂) and cardiac output were measured before and after training, and peak Vo₂ was determined again after 1 year.
Results After 2 months of training peak Vo₂ increased 25%, Vo₂ at the lactate threshold increased 40%, and maximal cardiac output increased from 12.1 ± 1.6 L/min to 13.9 ± 2.4 L/min in the exercise group (all p < 0.05), whereas no differences were observed in the control group. At the 1-year follow-up no further increases in peak Vo₂ were noted in either group, but the higher value persisted in the trained group. However, changes in limb flow rates were poorly related to changes in both peak Vo₂ and maximal cardiac output. Improvements in baseline and postischemic flow rates occurred mainly in the lower limbs and were observed in the two groups to a similar degree.
Conclusion Exercise training is highly effective in improving exercise capacity in patients with reduced ventricular function after myocardial infarction. These improvements parallel an increase in maximal cardiac output, but they are unrelated to vasodilatory capacity. In patients with reduced ventricular function after myocardial infarction, lower limb vasodilatory capacity improves gradually over the subsequent year, and these improvements occur irrespective of exercise training. (Am Heart J 1998;136:22-30.)
Sustained improvement in functional capacity after removal of body fluid with isolated ultrafiltration in chronic cardiac insufficiency: Failure of furosemide to provide the same result
1994, The American Journal of Medicine
objectives: This study was designed to investigate whether a subclinical accumulation of fluid in the lung interstitium associated with moderate congestive heart failure interferes with the patient's functional capacity, and whether furosemide treatment can promote reabsorption of the excessive fluid.
background: In patients with moderate congestive heart failure, pulmonary overhydration may be detected by chest roentgenography even if therapy is optimized to keep the urinary output normal and to prevent weight gain and dependent edema formation. Removal of the overhydration may help define its significance.
methods: Patients, whose regimens of digoxin, oral furosemide, and angiotensin-converting enzyme (ACE) inhibitor therapy were kept constant, were randomly allocated to receive ultrafiltration (8 cases) or an intravenous bolus of supplemental furosemide (mean dose: 248 mg; 8 cases). The amount of body fluid removed with each method approximated 1600 mL. Functional performance was assessed with cardiopulmonary exercise tests.
results: Soon after fluid withdrawal by either method, the filling pressures of the two ventricles and body weight were reduced and plasma renin activity, norepinephrine, and aldosterone were augmented. After furosemide administration, hormone levels remained elevated for the next 4 days, and during this period, patients had positive water metabolism, recovery of the elevated ventricular filling pressures, and reoccurrence of lung congestion with no improvement in functional capacity. After ultrafiltration, levels of renin, norepinephrine, and aldosterone fell to below control values within the first 48 hours and water metabolism was equilibrated at a new set point (less fluid intake and diuresis without weight gain). The favorable circulatory and ventilatory adjustments consequent to the reabsorption of lung water improved the functional capacity of these patients. That may also have restored the lung's ability to clear norepinephrine, thus restraining its facilitation of renin release. The improvement continued 3 months after the procedure.
conclusions: In patients with congestive heart failure the set point of fluid balance is altered in spite of oral furosemide therapy; supplemental intravenous furosemide does not shift the set point, at least not when combined with ACE inhibition. Excessive, although asymptomatic, lung water limits the functional capacity of the patient.
Effect of delayed captopril therapy on left ventricular mass and myonecrosis during acute coxsackievirus murine myocarditis
1990, American Heart Journal
The effect of captopril on coxsackievirus B3 murine myocarditis was investigated. Thirty-two, 3-week-old mice were infected with coxsackievirus B3 on day 0 of the study, then randomized into a placebo group or a captopril group starting on day 3 of infection. On day 9 of infection, the mice were put to death. Hearts were weighed and processed for light microscopic examination. Heart weight was 125 ± 19 mg in the control group versus 102 ± 14 mg in the captopril group (p < 0.0003). Amount of necrosis as a percentage of left ventricular section was 3.5% (2.0% to 7.5%) in the placebo group versus 2.0% (0.0% to 5.0%) in the captopril group (p < 0.01). The amount of dystrophic calcification was 5.0% (0.0% to 27.5%) in the placebo group versus 1.3% (0.0% to 20.0%) in the captopril group (p < 0.01). The extent of the histopathologic involvement by planimetry was 10.2% in the placebo group versus 5.4% in the captopril group (p = 0.052). We conclude that captopril is beneficial in decreasing left ventricular mass and the amount of myocardial necrosis and calcification in the short term in the murine myocarditis model.
Relationship between mixed venous oxygen saturation and cardiac index in patients with chronic congestive heart failure
1989, Chest
The use of mixed venous oxygen saturation ( $S \bar{v} O_{2}$ ) in patients with chronic congestive heart failure (CHF) has been advocated to analyze the action of therapy on cardiac index (CI). To evaluate the relationship between CI and $S \bar{v} O_{2}$ , ten CHF patients (mean age 65 years) were studied before and one, two, three, four (T4), six, eight and 24 hours after oral administration of an angiotensin converting enzyme (ACE) inhibitor (perindopril, 4 mg). At T4, a 12 percent increase in CI (p<0.01) was associated with a 16 percent decrease in arteriovenous oxygen difference (p<0.01), a 13 percent increase in mixed venous oxygen pressure ( $P \bar{v} O2$ ) (p<0.01), and a 9 percent increase in $S \bar{v} O_{2}$ (p<0.05) with no significant change in arterial oxygen pressure. There was no correlation between CI and $S \bar{v} O_{2}$ (r = 0.22) and between CI and $P \bar{v} O_{2}$ (r=0.23). Individual analyses were performed and patients were divided into two groups based on CI versus $S \bar{v} O_{2}$ r value; group 1, n = 6, r>0.65 (0.65-0.90), group 2, n = 4, r<0.65 (0.14-0.20). The lack of correlation in group 2 was due to a drug-dependent increase in oxygen consumption ( $\dot{V} o_{2}$ ) +18 percent vs –3 percent in group 1 (p<0.05) associated with a lack of increase in $P \bar{v} O_{2}$ +3 percent vs +14 percent in group 1 (p<0.05) despite a similar increase in oxygen availability +19 percent versus + 16 percent. It was concluded that (1) a correlation between CI and $S \bar{v} O_{2}$ is not found in every patient with CHF; (2) the lack of correlation in four out of our ten patients was due to an associated and significant increase in CI and $\dot{V} o_{2}$ in group 2; (3) group 2 patients probably had an important oxygen debt before treatment; (4) $S \bar{v} O_{2}$ cannot be used instead of CI to determine the hemodynamic consequences of the use of cardiovascular drugs.
Skeletal muscle blood flow, metabolism and morphology in chronic congestive heart failure and effects of short- and long-term angiotensin-converting enzyme inhibition
1988, The American Journal of Cardiology
Blood flow to skeletal muscle during exercise is limited in patients with chronic congestive heart failure compared with normal persons. This may, in part, be attributed to the inability of the vessels to dilate adequately. In addition, an abnormal skeletal muscle metabolism with oxidative capacity can be demonstrated in patients with chronic congestive heart failure. The latter may partially explain why vasodilators and inotropes that improve central hemodynamics, global leg perfusion or skeletal muscle blood flow during exercise do not increase oxygen uptake by working muscle after acute drug administration. Furthermore, increases in blood flow to skeletal muscle may be redistributed to inactive or less oxygen-dependent muscle fibers. Although acute angiotensin-converting enzyme inhibition usually neither exerts substantial improvement in exercise hemodynamics nor interferes with leg perfusion during exercise, skeletal muscle blood flow and oxygen uptake gradually increases with long-term angiotensin-converting enzyme therapy, leading to improved systemic oxygen consumption and exercise tolerance. Several factors, such as reduction in plasma and vascular angiotensin II and sympathetic nervous activity, increased prostaglandin levels and renal function may contribute to this beneficial long-term effect.
SYMPTOMATIC ASSESSMENT OF PATIENTS WITH HEART FAILURE: DOUBLE-BLIND COMPARISON OF INCREASING DOSES OF DIURETICS AND CAPTOPRIL IN MODERATE HEART FAILURE
1986, The Lancet
Ten patients with moderate heart failure - who still had symptoms despite 40 mg frusemide daily were treated with increased doses of frusemide and the addition of captopril in randomised order. Four different methods were used to assess the patients' response to treatment. Both treatments improved symptom-limited exercise tolerance, higher-dose frusemide having a more favourable effect. Perceived exertion during submaximal exercise was reduced by similar amounts by both treatments. The time taken to walk 100 m at a self-selected slow speed was reduced by both treatments; again higher-dose frusemide had a more beneficial effect. The higher dose of frusemide also had a more favourable effect on visual analogue scores for dyspnoea, fatigue, and general well-being.

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EFFECTS OF CAPTOPRIL ON ABNORMALITIES OF THE PERIPHERAL CIRCULATION AND RESPIRATORY FUNCTION IN PATIENTS WITH SEVERE HEART FAILURE

Abstract

Am J Med

Am J Cardiol

Am Heart J

Captopril therapy for heart failure

Lancet