Does impaired O2 delivery during exercise accentuate central and peripheral fatigue in patients with coexistent COPD-CHF?

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.

Keywords: chronic heart failure; chronic obstructive pulmonary disease; oxygenation; respiratory muscle; skeletal muscle.

Figures

Figure 1

Schematic representation of potential negative cardiopulmonary interactions in moderate to severe COPD. Increases in mean intra-thoracic pressure (ITP) and large swings in pleural pressure (PPL) may reduce venous return and right ventricular (RV) preload. High PPL swings, compression of juxta-alveolar capillaries and hypoxic vasoconstriction increase RV afterload and intra-cavitary pressures. The latter occurrence, in association with extrinsic compression of the right heart by the overdistended lungs, can impair RV relaxation and displace the inter-ventricular septum to the left. Reduced left heart filling pressures and dimensions may contribute to further impairments in stroke volume (SV). Large PPL swings can also increase left ventricular (LV) afterload secondary to high transmural pressures (PTM). Moreover, decreased aortic impedance and augmented systemic vascular resistance (SVR) further increase LV afterload, thus compromising cardiac output (Q˙t). Of note, the relative contribution of each of the above factors is likely to vary according to different phases of respiratory and cardiac cycles.

Figure 2

Schematic representation of potential implications of abnormal pulmonary gas exchange and central hemodynamics on central nervous system (brain) and peripheral skeletal muscle function during exercise in combined COPD-CHF. Compromised O2 delivery to brain and active limb muscles can occur as a consequence of impairments in gas exchange (e.g., ↓arterial O2 pressure; PaO2) and/or decreased cardiac output (Q˙t) and thus blood flow. A large fraction of an already reduced Q˙t can be directed to the overloaded respiratory muscles (due to ↑work of breathing), therefore further decreasing active limb muscle perfusion and accentuating peripheral fatigue. Solid black lines indicate that increased afferent information from the respiratory/peripheral muscles and/or impaired cerebral oxygenation may decrease motor drive (i.e., central fatigue). In this context, it is conceivable that central and peripheral fatigue potentiate each other and contribute to early exercise cessation in coexistent COPD-CHF.