Effects of enalapril in heart failure: a double blind study of effects on exercise performance,renal function,hormones, and metabolic state.

Several studies have shown symptomatic and haemodynamic improvement after the introduction of angiotensin converting enzyme inhibitors in patients with heart failure treated with diuretics. The concomitant long term effects of the new orally effective long acting angiotensin converting enzyme inhibitor, enalapril, on symptoms, exercise performance, cardiac function, arrhythmias, hormones, electrolytes, body composition, and renal function have been further assessed in a placebo controlled double blind cross over trial with treatment periods of eight weeks. Twenty patients with New York Heart Association functional class II to IV heart failure who were clinically stable on digoxin and diuretic therapy were studied. Apart from the introduction of enalapril, regular treatment was not changed over the study period; no order or period effects were noted. Enalapril treatment significantly improved functional class, symptom score for breathlessness, and exercise tolerance. Systolic blood pressure was significantly lower on enalapril treatment. Echocardiographic assessment indicated a reduction in left ventricular dimensions and an improvement in systolic time intervals. In response to enalapril, the plasma concentration of angiotensin II was reduced and that of active renin rose; plasma concentrations of aldosterone, vasopressin, and noradrenaline fell. There were significant increases in serum potassium and serum magnesium on enalapril. Glomerular filtration rate measured both by isotopic techniques and by creatinine clearance declined on enalapril while serum urea and creatinine rose and effective renal plasma flow increased. Body weight and total body sodium were unchanged indicating that there was no overall diuresis. There was a statistically insignificant rise in total body potassium, though the increase was related directly to pretreatment plasma renin (r = 0.5). On enalapril the improvement in symptoms, exercise performance, fall in plasma noradrenaline, and rise in serum potassium coincided with a decline in the frequency of ventricular extrasystoles recorded during ambulatory monitoring. Adverse effects were few. In patients with heart failure, enalapril had a beneficial effect on symptoms and functional capacity. The decline in glomerular filtration rate on enalapril may not be beneficial in early heart failure.     

Induction of a reduction in haemoglobin concentration by enalapril in stable, moderate heart failure: a double blind study

OBJECTIVE--To study the long term effects (12 weeks) of enalapril on central haemodynamic function and on arterial oxygen content and its determinants--haemoglobin concentration and oxygen saturation--in patients with stable moderate heart failure. DESIGN--Double blind placebo controlled randomised study. PATIENTS--17 patients with stable moderate heart failure caused by dilated cardiomyopathy which was treated with diuretics and digoxin. METHODS--Central haemodynamic function, arterial oxygen content, arterial haemoglobin concentration, and arterial oxygen saturation were measured at rest and during submaximal exercise. Plasma volume and total body haemoglobin were determined at rest. RESULTS--With enalapril treatment heart rate, pulmonary capillary wedge pressure, mean arterial pressure, and systemic vascular resistance decreased significantly both at rest and during submaximal exercise. Cardiac output did not change at rest but tended to increase (p = 0.06) during submaximal exercise. Arterial oxygen saturation remained unchanged while haemoglobin concentration and arterial oxygen content were significantly reduced. Total body haemoglobin was significantly reduced but the plasma volume remained unchanged. At rest, the reduction in arterial oxygen content resulted in a significantly reduced mixed venous oxygen content. However, during submaximal exercise the increase in cardiac output fully compensated for the reduction in arterial oxygen content and this effect was indicated by the unaltered mixed venous oxygen content. No changes were found in the placebo group after twelve weeks. CONCLUSIONS--Enalapril unloads the heart and reduces haemoglobin concentration. During submaximal exercise, the improvement in systemic blood flow was counterbalanced by this negative effect on the oxygen carrying capacity and systemic oxygen delivery was unchanged.     

Induction of a reduction in haemoglobin concentration by enalapril in stable, moderate heart failure: a double blind study.

OBJECTIVE--To study the long term effects (12 weeks) of enalapril on central haemodynamic function and on arterial oxygen content and its determinants--haemoglobin concentration and oxygen saturation--in patients with stable moderate heart failure. DESIGN--Double blind placebo controlled randomised study. PATIENTS--17 patients with stable moderate heart failure caused by dilated cardiomyopathy which was treated with diuretics and digoxin. METHODS--Central haemodynamic function, arterial oxygen content, arterial haemoglobin concentration, and arterial oxygen saturation were measured at rest and during submaximal exercise. Plasma volume and total body haemoglobin were determined at rest. RESULTS--With enalapril treatment heart rate, pulmonary capillary wedge pressure, mean arterial pressure, and systemic vascular resistance decreased significantly both at rest and during submaximal exercise. Cardiac output did not change at rest but tended to increase (p = 0.06) during submaximal exercise. Arterial oxygen saturation remained unchanged while haemoglobin concentration and arterial oxygen content were significantly reduced. Total body haemoglobin was significantly reduced but the plasma volume remained unchanged. At rest, the reduction in arterial oxygen content resulted in a significantly reduced mixed venous oxygen content. However, during submaximal exercise the increase in cardiac output fully compensated for the reduction in arterial oxygen content and this effect was indicated by the unaltered mixed venous oxygen content. No changes were found in the placebo group after twelve weeks. CONCLUSIONS--Enalapril unloads the heart and reduces haemoglobin concentration. During submaximal exercise, the improvement in systemic blood flow was counterbalanced by this negative effect on the oxygen carrying capacity and systemic oxygen delivery was unchanged.     

Hemodynamic and metabolic effects of enalapril in patients with heart failure

Placebo and enalapril were added on a double-blind basis to conventional treatment in 14 patients with congestive heart failure (CHF), New York Heart Association class II-III. The patients were followed for 14 weeks and their performance was evaluated by a treadmill test, ejection fraction by nuclear scan, cardiothoracic ratio, and Yale Scale score. Metabolic studies were done to test any adverse effects of the drugs. Enalapril decreased arterial pressure and cardiothoracic ratio, and increased ejection fraction. Placebo exerted no significant effects. However, both drugs improved treadmill time and Yale Scale score. No adverse metabolic or clinical effects were observed with either drug. Based on these limited observations we conclude that: (1) Enalapril is a useful ancillary agent to conventional treatment of CHF; (2) it exerts its effects through afterload and preload reduction; and (3) it is safe and well tolerated and has a prolonged duration of action.     

Vasodilatation with captopril and prazosin in chronic heart failure: double blind study at rest and on exercise

A double blind cross over study was performed to compare the long term hormonal, haemodynamic, and clinical responses to specific inhibition of the renin-angiotensin-aldosterone system (captopril) and of the alpha 1 adrenoceptors of the sympathetic system (prazosin) both at rest and during upright exercise in patients with chronic heart failure. Sixteen patients completed one month's treatment with each drug. During conventional diuretic treatment (control) plasma renin activity, aldosterone, and noradrenaline were increased at rest and on exercise. Control left ventricular filling pressures were raised, and correlated significantly with plasma renin activity both at rest and on exercise. Systemic vascular resistance was increased at rest, and its reduction during exercise correlated inversely with the increase in plasma renin activity and plasma noradrenaline. After one month's treatment with captopril there were reductions in plasma aldosterone, weight, left ventricular filling pressure, and systemic vascular resistance at rest and on exercise. Dyspnoea was relieved and exercise capacity increased. The greater fall in systemic vascular resistance on exercise no longer correlated with the increase in plasma renin activity. During treatment with prazosin there were increases in plasma noradrenaline and, transiently, in plasma aldosterone. Fluid retention occurred, and left ventricular filling pressure was unchanged. Compared with control values systemic vascular resistance was reduced at rest but not on exercise. Dyspnoea and exercise capacity did not improve. In chronic heart failure, vasodilatation by inhibition of the alpha adrenergic system with prazosin causes compensatory stimulation of the renin-angiotensin-aldosterone system and does not result in clinical benefit. Inhibition of the renin-angiotensin-aldosterone system with captopril causes secondary vasodilatation at rest and on exercise and results in improvement in symptoms and exercise capacity.     

Vasodilatation with captopril and prazosin in chronic heart failure: double blind study at rest and on exercise.

A double blind cross over study was performed to compare the long term hormonal, haemodynamic, and clinical responses to specific inhibition of the renin-angiotensin-aldosterone system (captopril) and of the alpha 1 adrenoceptors of the sympathetic system (prazosin) both at rest and during upright exercise in patients with chronic heart failure. Sixteen patients completed one month's treatment with each drug. During conventional diuretic treatment (control) plasma renin activity, aldosterone, and noradrenaline were increased at rest and on exercise. Control left ventricular filling pressures were raised, and correlated significantly with plasma renin activity both at rest and on exercise. Systemic vascular resistance was increased at rest, and its reduction during exercise correlated inversely with the increase in plasma renin activity and plasma noradrenaline. After one month's treatment with captopril there were reductions in plasma aldosterone, weight, left ventricular filling pressure, and systemic vascular resistance at rest and on exercise. Dyspnoea was relieved and exercise capacity increased. The greater fall in systemic vascular resistance on exercise no longer correlated with the increase in plasma renin activity. During treatment with prazosin there were increases in plasma noradrenaline and, transiently, in plasma aldosterone. Fluid retention occurred, and left ventricular filling pressure was unchanged. Compared with control values systemic vascular resistance was reduced at rest but not on exercise. Dyspnoea and exercise capacity did not improve. In chronic heart failure, vasodilatation by inhibition of the alpha adrenergic system with prazosin causes compensatory stimulation of the renin-angiotensin-aldosterone system and does not result in clinical benefit. Inhibition of the renin-angiotensin-aldosterone system with captopril causes secondary vasodilatation at rest and on exercise and results in improvement in symptoms and exercise capacity.     

Synergistic efficacy of enalapril and losartan on exercise performance and oxygen consumption at peak exercise in congestive heart failure

Oxygen consumption at peak exercise (peak VO2) is a strong independent predictor of the outcome in congestive heart failure (CHF). Renin-angiotensin system inhibition with either ACE or AT1 receptor blockers is effective on peak VO2. We evaluated whether mechanisms are similar for the 2 categories of drugs and whether their combination is able to produce a synergistic effect. Twenty CHF patients were randomized to receive, in a double-blind fashion, placebo + placebo (P+P), enalapril (20 mg/day) + placebo (E+P), losartan (50 mg/day) + placebo (L+P), and enalapril + losartan (E+L) or the same preparations in a reverse order, each for 8 weeks. Two patients did not complete the trial. Pulmonary function, cardiopulmonary exercise test, plasma neurohormones, and quality of life were assessed at the end of each treatment. Compared with P+P, E+P, and L+P similarly (16% and 15%, respectively) and significantly (p <0.01) augmented peak VO2. Enalapril improved lung function (reduced slope of ventilation vs carbon dioxide production and dead space to tidal volume ratio, and increased alveolar membrane conductance and tidal volume). Losartan likely activated the exercising muscle perfusion (raised delta VO2/delta work rate, which is a measure of aerobic work efficiency). In combination, they further increased peak VO2, 10% from E+P (p <0.05) and 11% from L+P (p <0.05). Compared with run-in, E+P and L+P significantly reduced plasma norepinephrine by 70 +/- 14 pg/ml and 100 +/- 16 pg/ml and aldosterone by 1.6 +/- 0.7 ng/dl and 1.6 +/- 0.8 ng/dl. These changes were significantly greater when the drugs were combined (140 +/- 20 pg/ml for norepinephrine, and 5.6 +/- 0.9 ng/dl for aldosterone). Quality-of-life score did not improve significantly at each treatment step. Thus, lorsartan and enalapril similarly increased peak VO2 in CHF patients, but mediators of this effect were, at least in part, different therapeutic targets that may be synergistic when the 2 drugs are combined.     

Treatment of heart failure with diuretics: body compartments, renal function and plasma hormones

Body fluid compartments, renal function and plasma hormoneswere measured in 13 patients with severe chronic heart failure,when the referring physician considered the patient to be appropriatelytreated. Although renal function was substantially impairedand plasma nor adrenaline, aldosterone and renin activity wereelevated, fluid compartments were within the normal range. Theseresults show that careful clinical assessment of patients byan experienced physician is a reliable method of assessing restorationof 'normal' body fluid volumes with diuretics.     

Effects of enalapril on myocardial noradrenaline overflow during exercise in patients with chronic heart failure

The effects of the angiotensin converting enzyme inhibitor enalapril on myocardial sympathetic tone, as represented by noradrenaline overflow, were studied in 14 men with congestive heart failure (mean ejection fraction 20%) in a double blind crossover comparison with placebo. Arterial and coronary sinus catecholamine concentrations and oxygen content, and coronary sinus blood flow, were measured at rest and during peak symptom limited upright exercise on a bicycle ergometer. There were no significant changes four hours after the first dose of enalapril, but after six weeks of treatment (10-20 mg/day) enalapril reduced myocardial overflow of noradrenaline at peak exercise. The external workload (exercise duration) increased from baseline values after both placebo and enalapril, and there was no difference between placebo and enalapril at six weeks. Heart work, however, was lower after enalapril: stroke work index was reduced at rest and the double product was lower at peak exercise. The reduction in maximal myocardial oxygen consumption after enalapril did not reach statistical significance. Coronary sinus adrenaline concentrations after enalapril and after placebo were not significantly different. The long term reduction of myocardial sympathetic activity on exercise may represent a significant benefit from angiotensin converting enzyme inhibition in heart failure and may reflect a reduced cardiac workload.     

Effects of exercise training on cardiac performance, exercise capacity and quality of life in patients with heart failure: a meta-analysis

BACKGROUND: Despite major advances in pharmacological treatment of chronic heart failure (CHF), a number of patients still suffer from dyspnoea, fatigue, diminished exercise capacity and poor quality of life. It is in this context that exercise training is being intensively evaluated for any additional benefit in the treatment of CHF. AIMS: To determine the effect of exercise training in patients with CHF on cardiac performance, exercise capacity and health-related quality of life. A meta-analysis was performed to obtain this goal. METHODS AND RESULTS: After including 35 randomised controlled trials, the methodological quality of each study was assessed, summary effect sizes (SESs) and the concomitant 95% confidence intervals (95% CI) were calculated for each outcome. Quantitative analysis showed statistically significant SESs, at rest, for diastolic blood pressure and end-diastolic volume. During maximal exercise, significant SESs were found for systolic blood pressure, heart rate, cardiac output, peak oxygen uptake, anaerobic threshold and 6-min walking test. The Minnesota Living with Heart Failure Questionnaire improved by an average of 9.7 points. CONCLUSIONS: Exercise training has clinically important effects on exercise capacity and HRQL, and may have small positive effects on cardiac performance during exercise.     

Effects of enalapril on myocardial noradrenaline overflow during exercise in patients with chronic heart failure.

The effects of the angiotensin converting enzyme inhibitor enalapril on myocardial sympathetic tone, as represented by noradrenaline overflow, were studied in 14 men with congestive heart failure (mean ejection fraction 20%) in a double blind crossover comparison with placebo. Arterial and coronary sinus catecholamine concentrations and oxygen content, and coronary sinus blood flow, were measured at rest and during peak symptom limited upright exercise on a bicycle ergometer. There were no significant changes four hours after the first dose of enalapril, but after six weeks of treatment (10-20 mg/day) enalapril reduced myocardial overflow of noradrenaline at peak exercise. The external workload (exercise duration) increased from baseline values after both placebo and enalapril, and there was no difference between placebo and enalapril at six weeks. Heart work, however, was lower after enalapril: stroke work index was reduced at rest and the double product was lower at peak exercise. The reduction in maximal myocardial oxygen consumption after enalapril did not reach statistical significance. Coronary sinus adrenaline concentrations after enalapril and after placebo were not significantly different. The long term reduction of myocardial sympathetic activity on exercise may represent a significant benefit from angiotensin converting enzyme inhibition in heart failure and may reflect a reduced cardiac workload.     

Comparison of the effects of losartan and enalapril on clinical status and exercise performance in patients with moderate or severe chronic heart failure

Objectives. This study assessed the feasibility of an efficacy trial comparing angiotensin-converting enzyme inhibition and angiotensin II receptor antagonism in heart failure. Patients with moderate or severe heart failure whose condition had previously been stabilized by treatment with a converting enzyme inhibitor were randomly assigned to receive enalapril or losartan. The study was designed to detect any signs of clinical deterioration during double-blind treatment.Background. Losartan is a specific, nonpeptide angiotensin II receptor-1 antagonist with a vasodilator hemodynamic profile similar to that of converting enzyme inhibitors. Although therapy with specific receptor blockade has certain theoretic advantages over nonspecific converting enzyme inhibition, demonstration of a comparable therapeutic effect in patients with congestive heart failure will require a major effort comparing two active agents.Methods. One hundred sixty-six patients with stable heart failure in New York Heart Association functional class III or IV and an ejection fraction ≤35% were included in a multicenter, double-blind, parallel, enalapril-controlled trial. After a 3-week stabilization period with optimal therapy, including digitalis, diuretic drugs and a converting enzyme inhibitor, patients were randomly assigned to 8 weeks of therapy with losartan, 25 mg/day (n = 52); losartan, 50 mg/day (n = 56); or enalapril, 20 mg/day (n = 58). Patients were assessed with frequent clinical and laboratory evaluation and exercise testing.Results. No significant differences between groups in terms of changes in exercise capacity (6-min walk test), clinical status (dyspnea-fatigue index), neurohumoral activation (norepinephrine, N-terminal atrial natriuretic factor), laboratory evaluation or incidence of adverse experience were observed.Conclusions. The results suggest that losartan and enalapril are of comparable efficacy and tolerability in the short-term treatment of moderate or severe congestive heart failure. A trial designed to compare the efficacy, tolerability and effect on mortality of long-term angiotensin II receptor blockade with converting enzyme inhibition is both feasible and ethically responsible.     

Acute and long-term effects of enalapril on the cardiovascular response to exercise and exercise tolerance in patients with congestive heart failure

Enalapril is a recently developed angiotensin-converting enzyme inhibitor that improves cardiac function at rest in patients with congestive heart failure. This study investigated the acute effects of enalapril on the cardiovascular response to exercise, and then evaluated the long-term effects of enalapril on exercise capacity and functional status during a 12 week placebo-controlled trial in patients with heart failure. Ten patients underwent hemodynamic monitoring while at rest and during incremental bicycle exercise before and after 5 to 10 mg of enalapril orally. At rest, enalapril decreased mean blood pressure 13% (p less than 0.01) and systemic vascular resistance 20% (p less than 0.05) and increased stroke volume index 21% (p less than 0.01). During maximal exercise, enalapril decreased systemic vascular resistance and increased both cardiac and stroke volume indexes. Enalapril acutely increased exercise duration (p less than 0.05) and maximal oxygen consumption (p less than 0.001). These 10 patients and an additional 13 patients were then randomized to either placebo or enalapril treatment and followed up for 12 weeks. Of the 11 patients assigned to active treatment, 73% considered themselves improved compared with 25% of the patients assigned to placebo treatment (p less than 0.02). During long-term treatment, exercise capacity increased in patients receiving enalapril (p less than 0.001) but was unchanged in patients receiving placebo (intergroup difference, p less than 0.05). During long-term treatment, no adverse effects of enalapril occurred. Thus, enalapril improves cardiac function at rest and during exercise. Compared with placebo, maintenance therapy with enalapril results in symptomatic improvement and increased exercise capacity.     

Haemodynamic, hormonal, and electrolyte effects of enalapril in heart failure.

Enalapril, the new converting enzyme inhibitor, was administered to eight patients with heart failure (NYHA Functional Class II to IV) during standardised and intensive haemodynamic, hormone, and electrolyte monitoring. The first dose (5 mg) of enalapril induced a fall in plasma angiotensin II and noradrenaline levels, and prolonged decrements in systemic vascular resistance, arterial pressure, heart rate, and right heart pressures. Maximum haemodynamic effects were evident four to eight hours after the first dose, with return to baseline by 24 hours. Plasma angiotensin II levels, however, were still suppressed at 24 hours. The magnitude of haemodynamic response was related closely to baseline (pre-enalapril) activity of the renin-angiotensin system and the sympathetic system. Enalapril treatment over three days induced a positive cumulative balance of sodium and potassium, and a small increase in plasma potassium. Urine aldosterone excretion decreased in a stepwise fashion. Continued enalapril administration for four to eight weeks resulted in improved clinical status (NYHA Functional Class) and exercise tolerance in patients who initially were most severely incapacitated, but little change was observed in healthier subjects. We conclude that in heart failure, enalapril is a long acting converting enzyme inhibitor with clear cut beneficial haemodynamic effects in the short term. Long term controlled studies of enalapril in heart failure are warranted.     

Comparison of captopril with enalapril in the treatment of heart failure: Influence on hemodynamics and measures of renal function

Summary Twenty-nine patients with severe heart failure (NYHA III) were randomly assigned to receive therapy with an angiotensin converting enzyme inhibitor (ACE inhibitor), either captopril or enalapril. The mean daily dosage of captopril was 56±5 mg and of enalapril 9.5±0.4 mg. After a mean of 8±1 days, the influence of both ACE inhibitors on hemodynamics and renal function was compared. The mean arterial pressure in the group treated with captopril (Group A) fell by 9±3 mmHg (p<0.01), and in the group treated with enalapril (Group B) it fell by 12±3 mmHg (p<0.001). The difference between the groups was not significant. Heart rate decreased in both groups; however, the change was significant (p<0.05) only in patients treated with enalapril (–11±3 bpm in Group B vs. –7±4 bpm in Group A). Stroke volume index increased by 6±3 ml/m² in Group A (p<0.05) vs. 10±2 ml/m² in Group B (p<0.01). The increase in stroke volume index was not significantly different between the two groups. Mean decreases in pulmonary artery and right atrial pressure were also comparable in both groups. Thus, hemodynamic improvements were similar during therapy with either captopril or enalapril. Serum sodium and potassium before therapy were 137±1 mmol/l and 4.1±0.1 mmol/l, respectively, in group A and 139±1 mmol/l and 4.0±0.1 mmol/l, respectively, in group B. Neither serum electrolytes nor serum creatinine were changed significantly by therapy with captopril or enalapril. These results suggest that despite differences in duration of action the effects on hemodynamics, serum electrolytes, and renal function are similar when comparable dosages of ACE inhibitors are used.     

Long-term therapy of heart failure with prazosin: a randomized double blind trial

There is evidence that repeated administration of prazosin to patients with severe congestive heart failure results in tolerance to its initial salutary effects as a vasodilator. Therefore, we used a randomized, double blind protocol to evaluate the clinical effectiveness of 2 months of continuous prazosin therapy in 22 patients with severe congestive heart failure. After 2 months, the patients treated with prazosin showed significant improvement in mean New York Heart Association functional class (3.7 ± 0.2 to 2.3 ± 0.2, p < 0.01), treadmill exercise duration (123 ± 30 to 209 ± 40 sec, p < 0.01), echocardiographic ejection fraction (31.8 ± 3.2 to 37.3 ± 4.2 percent, p < 0.01), stroke excursion (1.02 ± 0.10 to 1.24 ± 0.14 cm, p < 0.01), mean velocity of circumferential fiber shortening (0.69 ± 0.07 to 0.80 ± 0.09 circumferences/sec, p < 0.06) and ejection fraction measured with radionuclide ventriculography (24.8 ± 2.2 to 32.1 ± 2.9 percent, p < 0.001). A comparable placebo-treated group showed no significant change in any index of functional or hemodynamic performance. The radionuclide ventriculographic ejection fraction fell to pretreatment levels 48 hours after the withdrawal of chronic prazosin therapy and rose to the long-term treatment level on readministration of the drug, thus confirming that the improvement observed after 2 months was due to prazosin. After 2 months there was clinical evidence of attenuation of the initial response to prazosin, although patients continued to show improvement over their pretreatment state. Prazosin-treated patients had an increase in plasma renin activity and required an increase in diuretic dose, suggesting that the renin-angiotensin system may contribute to the observed attenuation of drug effect. Long-term therapy with prazosin results in significant functional and hemodynamic improvement in patients with severe congestive heart failure.     

Hemodynamic, ventilatory and metabolic effects of light isometric exercise in patients with chronic heart failure

Light isometric exercise, such as lifting or carrying loads that require 25% of a maximal voluntary contraction, is frequently reported to cause dyspnea in patients with heart failure. The pathophysiologic mechanisms responsible for the appearance of this symptom, however, are unknown. Accordingly, hemodynamic, metabolic and ventilatory responses to 6 min of light isometric forearm exercise were examined and compared in 20 patients with chronic heart failure and abnormal ejection fraction (24 +/- 9%) and 17 normal individuals. In contrast to findings in normal volunteers, exercise cardiac index did not increase whereas exercising forearm and mixed venous lactate concentrations increased (p less than 0.05) above levels at rest in patients with heart failure; at 90 s of recovery, blood lactate concentration remained elevated (p less than 0.05). The venous lactate concentration of the nonexercising arm, unlike that of the exercising forearm, was not altered. Oxygen uptake, carbon dioxide production and minute ventilation increased similarly in patients and normal subjects during exercise, but only in patients did each increase further (p less than 0.05) during recovery. Thus, in patients with heart failure, light isometric forearm exercise represents an anaerobic contraction with lactate production. The subsequent increase in carbon dioxide production leads to a disproportionate increase in minute ventilation and oxygen uptake during recovery that may be perceived as breathlessness.     

Effect of long-term enalapril therapy on cardiopulmonary exercise performance in men with mild heart failure and previous myocardial infarction.

Forty-one men with documented myocardial infarction greater than 6 months previously were randomized to long-term (48 weeks) therapy with placebo or enalapril on a double-blind basis. All patients were receiving concurrent therapy with digitalis and a diuretic drug for symptomatic heart failure (functional class II or III). The mean age was 64 +/- 7.3 years and no patient suffered from exertional chest pain. Patients underwent maximal cardiopulmonary exertional chest pain. Patients underwent maximal cardiopulmonary exercise testing to exhaustion on an ergometer cycle nine times over the course of 48 weeks. Gas exchange data were collected on a breath by breath basis with use of a continuous ramp protocol. In the placebo group (n = 21), the mean (+/- SD) peak oxygen consumption (VO2) at baseline was 18.8 +/- 5.2 versus 18.5 +/- 5.5 ml/kg per min at 48 weeks (-1.4%, p = NS). In the enalapril group (n = 20), the corresponding values were 18.1 +/- 3.1 versus 18.3 +/- 2.6 ml/kg per min (+2.8%, p = NS). The mean VO2 at the anaerobic threshold for the placebo group at baseline study was 13.1 +/- 3.5 versus 12.8 +/- 2.1 ml/kg per min at 48 weeks (-2.2%, p = NS). The corresponding values for the enalapril group were 11.8 +/- 2.3 versus 11.8 +/- 2.4 ml/kg per min (+1.4%, p = NS). The mean total exercise duration in the placebo group at baseline study was 589 +/- 153 versus 620 +/- 181 s at 48 weeks (+5.4%, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)