Mechanism of augmented exercise hyperpnea in chronic heart failure and dead space loading

Abstract

Patients with chronic heart failure (CHF) suffer increased alveolar VD/VT (dead-space-to-tidal-volume ratio), yet they demonstrate augmented pulmonary ventilation such that arterial PCO2 (PaCO2) remains remarkably normal from rest to moderate exercise. This paradoxical effect suggests that the control law governing exercise hyperpnea is not merely determined by metabolic CO2 production (V̇CO2) per se but is responsive to an apparent (real-feel) metabolic CO2 load false(V˙normalCO2ofalse) that also incorporates the adverse effect of physiological VD/VT on pulmonary CO2 elimination. By contrast, healthy individuals subjected to dead space loading also experience augmented ventilation at rest and during exercise as with increased alveolar VD/VT in CHF, but the resultant response is hypercapnic instead of eucapnic, as with CO2 breathing. The ventilatory effects of dead space loading are therefore similar to those of increased alveolar VD/VT and CO2 breathing combined. These observations are consistent with the hypothesis that the increased series VD/VT in dead space loading adds to V˙normalCO2o as with increased alveolar VD/VT in CHF, but this is through rebreathing of CO2 in dead space gas thus creating a virtual (illusory) airway CO2 load within each inspiration, as opposed to a true airway CO2 load during CO2 breathing that clogs the mechanism for CO2 elimination through pulmonary ventilation. Thus, the chemosensing mechanism at the respiratory controller may be responsive to putative drive signals mediated by within-breath PaCO2 oscillations independent of breath-to-breath fluctuations of the mean PaCO2 level. Skeletal muscle afferents feedback, while important for early-phase exercise cardioventilatory dynamics, appears inconsequential for late-phase exercise hyperpnea.

Ventilatory Response to Carbon Dioxide Output in Subjects With Congestive Heart Failure and in Patients with COPD With Comparable Exercise Capacity

“…The mechanisms underlying the control of exercise hyperpnoea are complex and still under investigation both in SEE THE RELATED EDITORIAL ON PAGE 1157 healthy subjects 5 and in cardiopulmonary patients. 6,7 Regardless of rate, the minute ventilation (V E ) for a given metabolic rate (V E /V CO 2 ), also known as ventilatory equiv-alent for CO 2 , 8 may be increased both in congestive heart failure and COPD during exercise. Notably, the slope of the V E /V CO 2 linear relationship is considered as the strongest prognostic marker (including peak V O 2 ) in patients with congestive heart failure, regardless of the etiology of cardiomyopathy, 9 and was found to be a significant postsurgical prognostic marker in patients with COPD undergoing lung resection.…”

“…Notably, the slope of the V E /V CO 2 linear relationship is considered as the strongest prognostic marker (including peak V O 2 ) in patients with congestive heart failure, regardless of the etiology of cardiomyopathy, 9 and was found to be a significant postsurgical prognostic marker in patients with COPD undergoing lung resection. 10 Moreover, it has been recently recognized that even the intercept of the V E /V CO 2 relationship may be relevant in fully understanding ventilatory control mechanisms in health 7 and in disease. 6,7 Up to now, no study has aimed to compare the ventilatory response to V CO 2 in subjects with congestive heart failure and COPD with comparable exercise capacity or to assess the possible discriminating value of V E /V CO 2 measurement in these patients.…”

“…10 Moreover, it has been recently recognized that even the intercept of the V E /V CO 2 relationship may be relevant in fully understanding ventilatory control mechanisms in health 7 and in disease. 6,7 Up to now, no study has aimed to compare the ventilatory response to V CO 2 in subjects with congestive heart failure and COPD with comparable exercise capacity or to assess the possible discriminating value of V E /V CO 2 measurement in these patients. The aim of the present study was to measure V E /V CO 2 in terms of both slope and intercept in a cohort of subjects with congestive heart failure and COPD and to ascertain whether the V E /V CO 2 slope and intercept may discriminate between these patients at equal peak V O 2 .…”

Exercise Ventilation-CO2Output Relationship in COPD and Heart Failure: A Tale of Two Abnormalities

“…This self-adaptive brain mechanism of controlling V E not only to match V CO 2 but also to compensate for increases in dead-space-to-tidal volume ratio that add to the burden of pulmonary CO 2 elimination has been likened to the temperature controller's well-acknowledged cognition and perception capability in compensating for the adverse influences of environmental factors (such as humidity and wind-chill factor) on heat transfer from the body that add to the burden of thermoregulation. 12 On the other hand, the dramatic rollback of the exercise V E -V CO 2 slope (with consequent development of CO 2 retention during exercise 8,11 ) in severe COPD vis-à-vis its monotonic increase (without CO 2 retention) in severe chronic heart failure once again reminds us of the often-forgotten fact that ventilatory control is strongly influenced by respiratory mechanical constraints rather than being totally reflex-driven, as commonly assumed. Indeed, reflexogenic drives such as peripheral chemoreflex or skeletal muscle metaboreflex per se are unlikely to be the cause of exercise hyperpnea, as interruption of the corresponding afferent pathways affects only the transient but not the steady-state ventilatory response to exercise (reviewed in Reference 12).…”

“…The answer to this critical question may call for a fundamental paradigm shift in viewing the brain mechanism for ventilatory control not as a simplistic knee-jerk reflex driver but as a self-adaptive intelligent controller capable of balancing such chemical and mechanical constraints in determining the optimal V E that meets the metabolic demand without causing excessive work of breathing. [12][13][14][15][16] In this light, patients with chronic heart failure, COPD, and other diseases may actually be much smarter in optimizing their breathing for self-survival than they have been traditionally given credit for in practice.…”