Alveolar-capillary membrane conductance is the best pulmonary function correlate of exercise ventilation efficiency in heart failure patients

ArticleinEuropean Journal of Heart Failure 7(6):1017-22 · November 2005with12 Reads
DOI: 10.1016/j.ejheart.2004.10.009 · Source: PubMed
In heart failure (HF), changes in lung mechanics and gas diffusion are limiting factors to exercise. Their contribution to an increased exercise ventilation to CO2 production (VE/VCO2) slope is undefined. A total of 67 stable HF patients underwent cardiopulmonary exercise and pulmonary function tests, including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), maximal voluntary ventilation (MVV), total lung capacity (TLC) and alveolar diffusing capacity with its subcomponents (alveolar-capillary membrane conductance (D(m)) and capillary blood volume (V(c))). Patients showed a mild restrictive pattern (FEV1=85+/-15% and FVC=75+/-13% of normal predicted) and a moderate D(m) reduction (32+/-12 ml min(-1) mm Hg(-1)). Average peak VO(2) was 15.6+/-4.0 ml min(-1) kg(-1) and the VE/VCO2 slope was 39.6+/-11.0. At simple Spearman correlation analysis, all variables, but V(c), correlated with peak VO2; only D(m) correlated with VE/VCO2 slope. At partial Spearman correlation, all variables lost the peak VO2 correlation, and D(m) still inversely correlated with VE/VCO2 slope (r=-0.35; p=0.005). In patients with a high VE/VCO2 slope (cutoff value 34), despite comparable lung volumes, D(m) was significantly more depressed (30+/-13 vs. 35+/-10 ml min(-1) mm Hg(-1); p<0.01). Pulmonary function tests and alveolar gas diffusing capacity poorly correlate with peak VO2. D(m) impairment rather than lung volumes correlates with exercise ventilation efficiency. This finding further adds to the pathophysiological relevance of an abnormal gas exchange in HF patients.
    • "In addition, within skeletal muscles the capacity to utilize O 2 can be impaired in more severe patients due to reductions in mitochondrial oxidative enzyme activity and volume density as well as mitochondrial dysfunction (Hirai et al., 1995; Belardinelli et al., 1997; Kindig et al., 1999; Diederich et al., 2002; Copp et al., 2010; Bowen et al., 2012; Poole et al., 2012). There is also evidence that CHF patients might develop pulmonary dysfunction including ventilation-perfusion ( ˙ V/ ˙ Q) mismatch (Agostoni et al., 2006), reduced O 2 diffusing capacity (Guazzi et al., 2005) and diminished respiratory muscle strength and endurance (Agostoni et al., 2002). While ˙ V/ ˙ Q mismatch and diffusive deficiencies may not always lead to arterial hypoxemia in CHF, restrictive and obstructive abnormalities combined with the sensitization of peripheral chemoreceptors (carotid bodies) result in increased work of breathing (Narkiewicz et al., 1999; Ponikowski et al., 2001). "
    [Show abstract] [Hide abstract] ABSTRACT: Impairment in oxygen (O2) delivery to the central nervous system (“brain”) and skeletal locomotor muscle during exercise has been associated with central and peripheral neuromuscular fatigue in healthy humans. From a clinical perspective, impaired tissue O2 transport is a key pathophysiological mechanism shared by cardiopulmonary diseases, such as chronic obstructive pulmonary disease (COPD) and chronic heart failure (CHF). In addition to arterial hypoxemic conditions in COPD, there is growing evidence that cerebral and muscle blood flow and oxygenation can be reduced during exercise in both isolated COPD and CHF. Compromised cardiac output due to impaired cardiopulmonary function/interactions and blood flow redistribution to the overloaded respiratory muscles (i.e., ↑work of breathing) may underpin these abnormalities. Unfortunately, COPD and CHF coexist in almost a third of elderly patients making these mechanisms potentially more relevant to exercise intolerance. In this context, it remains unknown whether decreased O2 delivery accentuates neuromuscular manifestations of central and peripheral fatigue in coexistent COPD-CHF. If this holds true, it is conceivable that delivering a low-density gas mixture (heliox) through non-invasive positive pressure ventilation could ameliorate cardiopulmonary function/interactions and reduce the work of breathing during exercise in these patients. The major consequence would be increased O2 delivery to the brain and active muscles with potential benefits to exercise capacity (i.e., ↓central and peripheral neuromuscular fatigue, respectively). We therefore hypothesize that patients with coexistent COPD-CHF stop exercising prematurely due to impaired central motor drive and muscle contractility as the cardiorespiratory system fails to deliver sufficient O2 to simultaneously attend the metabolic demands of the brain and the active limb muscles.
    Full-text · Article · Jan 2015
    • "In heart failure (HF), gradual accumulation of fluid across the lungs leads to a decrease of gas exchange capacity [13] presumably when fluid accumulation in the interstitial space and reabsorption by alveolar Na+ transport systems are fully exploited. Under these conditions, reduced DLCO and/or DM have been consistently reported to be associated to a reduced exercise capacity [13], [14], reduced ventilatory efficiency [15] and poor prognosis [16]. β-blockers are among the cornerstone tools for HF treatment [17], [18] but substantial functional differences have been documented within this class of medications. "
    [Show abstract] [Hide abstract] ABSTRACT: In experimental conditions alveolar fluid clearance is controlled by alveolar β2-adrenergic receptors. We hypothesized that if this occurs in humans, then non-selective β-blockers should reduce the membrane diffusing capacity (DM), an index of lung interstitial fluid homeostasis. Moreover, we wondered whether this effect is potentiated by saline solution infusion, an intervention expected to cause interstitial lung edema. Since fluid retention within the lungs might trigger excessive ventilation during exercise, we also hypothesized that after the β2-blockade ventilation increased in excess to CO2 output and this was further enhanced by interstitial edema. 22 healthy males took part in the study. On day 1, spirometry, lung diffusion for carbon monoxide (DLCO) including its subcomponents DM and capillary volume (VCap), and cardiopulmonary exercise test were performed. On day 2, these tests were repeated after rapid 25 ml/kg saline infusion. Then, in random order 11 subjects were assigned to oral treatment with Carvedilol (CARV) and 11 to Bisoprolol (BISOPR). When heart rate fell at least by 10 beats·min(-1), the tests were repeated before (day 3) and after saline infusion (day 4). CARV but not BISOPR, decreased DM (-13±7%, p = 0.001) and increased VCap (+20±22%, p = 0.016) and VE/VCO2 slope (+12±8%, p<0.01). These changes further increased after saline: -18±13% for DM (p<0.01), +44±28% for VCap (p<0.001), and +20±10% for VE/VCO2 slope (p<0.001). These findings support the hypothesis that in humans in vivo the β2-alveolar receptors contribute to control alveolar fluid clearance and that interstitial lung fluid may trigger exercise hyperventilation.
    Full-text · Article · Apr 2013
    • "This implies an increased ventilatory effort as a measure of early CO 2 -production. Mainly three mechanisms for augmented ventilatory efforts to CO 2 production have been reported in the past: Increased deadspace volume due to ventilation-perfusion-mismatching (Guazzi et al., 2005a,b), altered chemoreflex and baroreflex sensitivity (Narkiewicz et al., 1999; Ponikowski et al., 1997) as well as an early occurrence of lactic acidosis Fig. 3 "
    [Show abstract] [Hide abstract] ABSTRACT: Cardiopulmonary exercise testing (CPET) provides insights into ventilatory, cardiac and metabolic dysfunction in heart and lung diseases and might play a role in cardiac risk stratification in major depressive disorder (MDD). The VE/VCO(2)-slope indicates ventilatory efficiency and has been applied to stratify the cardiac risk in heart failure (HF). Therefore, the current study was conducted to evaluate and classify ventilatory efficiency and its relationship to physical fitness and disease severity in MDD. Exhaustive incremental exercise testing was completed by 15 female MDD patients and pair matched controls. The ventilatory threshold (VT) and the VE/VCO(2)-slope were assessed. Statistical analyses were conducted by means of MANOVAs and follow-up univariate ANOVAs. In patients with MDD, significant different relative work rates and oxygen uptakes at the VT in comparison to healthy controls were observed. Furthermore, we found an increased VE/VCO(2)-slope in depressed patients. We additionally report an inverse relationship between the VE/VCO(2)-slope and peak power output as well as peak oxygen uptake solely in patients. We did not observe any association of assessed parameters with disease severity. CPET measures indicate ventilatory inefficiency in patients with MDD. The elevated VE/VCO(2)-slope indicates that patients with MDD need to ventilate significantly more to a given amount of developing CO(2). Further investigations are needed to verify the application of the ventilatory classification system to stratify cardiovascular risk in depressive disorder.
    Full-text · Article · Aug 2010
Show more