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

Cardiopulmonary Laboratory, University of Milano, Cardiology Division, San Paolo Hospital, Via A. di Rudiní, 8, 20142, Milano, Italy.
European Journal of Heart Failure (Impact Factor: 6.58). 11/2005; 7(6):1017-22. DOI: 10.1016/j.ejheart.2004.10.009
Source: PubMed

ABSTRACT 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.

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    • "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). "
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    • "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 "
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