Biomedical subjects

G Pontone

Publications and source records attributed to G Pontone.

6 recordsLinked to original sources

PubMed1999

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.

Adult↗

PubMed1999

Aspirin worsens exercise performance and pulmonary gas exchange in patients with heart failure who are taking angiotensin-converting enzyme inhibitors.

BACKGROUND: Pulmonary function abnormalities participate in causing exercise disability in patients with congestive heart failure (CHF). Impaired pulmonary gas transfer is one of these abnormalities. Angiotensin-converting enzyme (ACE) inhibitors improve diffusion for carbon monoxide and exercise capacity, an effect that is seemingly mediated through prostaglandin activation because it is inhibited by cyclooxygenase blockade with aspirin. This suggests the possibility that aspirin may disturb the pulmonary function and exercise ability in CHF, at least in those patients who are taking ACE inhibitors. This study was aimed at probing this hypothesis. METHODS: A dose of 325 mg aspirin was given daily for 8 weeks to 26 consecutive patients with primary dilated cardiomyopathy (New York Heart Association class II or III) whose current outpatient antifailure therapy included (group 1, 18 cases) or did not include (group 2, 8 cases) an ACE inhibitor in addition to digoxin and furosemide. During the study ACE inhibition was continued in group 1 by giving enalapril 20 mg daily. RESULTS: Tests repeated at 8 weeks proved that aspirin was deleterious in group 1. Compared with run-in, rest carbon dioxide, peak exercise oxygen uptake (peak VO(2 )), and tidal volume levels were diminished in this group; the ratio of exercise minute ventilation to carbon dioxide production (VE/VCO(2)) was augmented and its variations were inversely related to those of peak VO(2). Similar results were not observed in group 2; however, once this part of the study was completed and enalapril was included in the current therapeutic regimen, an inhibitory effect of aspirin on carbon dioxide, peak VO(2), peak tidal volume, and VE/VCO(2) at 1 L levels became evident and was similar to that observed in group 1. CONCLUSIONS: Aspirin does not affect ventilation efficiency and peak VO(2 ) in patients with CHF not taking ACE inhibitors, but it worsens the pulmonary diffusion for carbon monoxide, VO(2 ), and the ventilatory response to exercise in the presence of ACE inhibition. This may be relevant in patients with CHF from ischemic heart disease. Whether the same may be true of smaller aspirin doses was not investigated in this study.

Aged↗

PubMed1999

Pulmonary function, cardiac function, and exercise capacity in a follow-up of patients with congestive heart failure treated with carvedilol.

BACKGROUND: Chronic heart failure causes disturbances in ventilation and pulmonary gas transfer that participate in limiting peak exercise oxygen uptake (VO(2p )). The beta-adrenergic receptor blocker carvedilol improves left ventricular (LV) function and not VO(2p). This study was aimed at investigating the pulmonary response to changes in LV performance produced by carvedilol in patients with chronic heart failure. METHODS: Twenty-one patients with New York Heart Association class II to III heart failure were randomly assigned (2 to 1) to carvedilol (25 mg twice daily, n = 14) or placebo (n = 7) for 6 months. Rest forced expiratory volume (FEV(1)), vital capacity, total lung capacity, carbon monoxide diffusing capacity, its alveolar-capillary membrane component, pulmonary venous and transmitral flows (for monitoring changes in LV end-diastolic pressure), LV diastolic and systolic dimensions, stroke volume, ejection fraction, and fiber shortening velocity were measured at baseline and at 3 and 6 months. VO(2p), peak ratio of dead space to tidal volume (VD/VT(p)), ventilatory equivalent for carbon dioxide production (VE/VCO(2)), and VO(2) at anaerobic threshold (VO(2at)) were also determined. RESULTS: FEV(1), vital capacity, total lung capacity, carbon monoxide diffusing capacity, and the alveolar-capillary membrane component were impaired in chronic heart failure compared with 14 volunteers and did not vary with treatment. Carvedilol reduced end-diastolic pressure, end-diastolic diameter, and end-systolic diameter and increased ejection fraction, stroke volume, and fiber shortening velocity without affecting VO(2p), VO(2at), VD/VT(p), or VE/VCO(2) at 3 and 6 months. Placebo did not produce significant changes. CONCLUSIONS: In chronic heart failure carvedilol ameliorates LV function at rest and does not significantly affect ventilation and pulmonary gas transfer or functional capacity. These results suggest that improvement in cardiac hemodynamics with carvedilol does not reverse pulmonary dysfunction. Persistent lung impairment might have some role in the failure of carvedilol to improve exercise performance.

Adrenergic beta-Antagonists↗

PubMed1999

Oxygen consumption.

It gets more and more frequent to use oxygen consumption (VO2) to evaluate exercise capacity and response to treatment in heart failure patients. The amount of VO2 is due to ventilation, oxygen transport and muscle activity. No one of these single steps can define by itself VO2, but all these physiological functions are integrated each other. In this paper we examine the modifications of cardiac output, arteriovenous oxygen content difference, and the temporal behavior of their variations during exercise in heart failure. We specifically describe changes in VO2 during simulated altitude; we also contemplate mechanisms governing oxygen diffusion from capillary bed to mitochondria and critical capillary PO2 concept.

Animals↗

PubMed1998

[A failed improvement in pulmonary function and exercise capacity with carvedilol in congestive heart failure despite an excellent effect on left ventricular function].

This study was aimed at investigating in chronic heart failure (CHF) the effects that beta-blockade with carvedilol may have on lung function, and their relationship with left ventricular (LV) performance and peak exercise oxygen uptake (VO2p). CHF causes disturbances in ventilation and pulmonary gas transfer (stress failure of alveolar-capillary membrane) that participate in limiting VO2p. Carvedilol improves LV function and not VO2p. Twenty-one NYHA functional class II-III patients were randomized (2 to 1) to carvedilol (25 mg bid., 14 patients) or placebo (7 patients) for 6 months. Rest forced expiratory volume (FEV1), vital capacity (VC), total lung capacity (TLC), carbon monoxide diffusing capacity (DLCO), its alveolar-capillary membrane component (DM), pulmonary venous and transmitral flows (for monitoring changes in LV end-diastolic pressure, EDP), LV diastolic (EDD) and systolic (ESD) dimensions, stroke volume (SV), ejection fraction (EF), fiber shortening velocity (VCF) were measured at baseline and at 3 and 6 months. VO2p, peak ratio of dead space to tidal volume (VD/VTp), ventilatory equivalent for CO2 production (VE/VCO2), VO2 at anaerobic threshold (VO2at) were also determined. FEV1, VC, TLC, DLCO, DM were impaired in CHF compared to 14 volunteers, and did not vary with treatment. Carvedilol reduced EDP, EDD, ESD, and increased EF, SV, VCF, without affecting VO2p, VO2at, VD/VTp, VE/VCO2, at 3 and 6 months. Placebo was ineffective. In CHF, carvedilol exerts neutral effects on ventilation and pulmonary gas transfer and ameliorates LV function at rest. This proves that antifailure treatment may not be similarly effective on cardiac and pulmonary function; and does not contradict the possibility that persistence of lung impairment may contribute to lack of improvement in exercise performance with carvedilol.

Adrenergic beta-Antagonists↗

PubMedDate not supplied

[Effectiveness of long-term ACE-inhibition on pulmonary diffusion and ventilation-perfusion ratio in chronic heart failure: correlation with physical performance].

Pulmonary dysfunction contributes to exercise intolerance in patients with chronic heart failure, and ACE-inhibition improves the functional capacity of these subjects. In this study, we investigated whether and how ACE-inhibitors affect pulmonary function and ventilatory response during exercise in chronic heart failure. Twenty patients with idiopathic dilated cardiomyopathy and left ventricular ejection fraction < 35% underwent pulmonary function tests and exercise evaluation with analysis of expired gases before and after 1 year of treatment with enalapril (10 mg bid). To explore whether or not the respiratory influence of ACE-inhibitors is peculiar to the syndrome of cardiac failure, we also studied 19 subjects with mild, untreated primary hypertension who followed the same protocol. In this group, enalapril exerted a neutral effect on pulmonary function. In chronic heart failure patients, lung volumes were abnormal and did not improve after enalapril treatment; on the contrary, alveolar diffusing capacity for carbon monoxide increased towards normal values. Exercise tolerance time, peak exercise oxygen consumption, ventilation, and tidal volume also improved and the dead space to tidal volume ratio was reduced at the peak exercise and intermediate exercise phases (20, 60 W). Changes in carbon monoxide diffusion were positively correlated to those occurring during peak exercise oxygen consumption. A negative correlation was found between the variations in oxygen consumption and those in dead space to tidal volume ratio at peak exercise. We conclude that in patients with chronic heart failure, ACE-inhibition restores diffusing lung properties and improves ventilation-perfusion matching during exercise. In this syndrome, sustained reduction in gas exchange resistance is a fundamental therapeutic property of this class of drugs.

Adult↗