Exercise training in chronic heart failure: improving skeletal muscle O2 transport and utilization

Chronic heart failure (CHF) impairs critical structural and functional components of the O-2 transport pathway resulting in exercise intolerance and, consequently, reduced quality of life. In contrast, exercise training is capable of combating many of the CHF-induced impairments and enhancing the matching between skeletal muscle O-2 delivery and utilization ((Q) over dot(mO2) and (V) over dot(mO2), respectively). The (Q) over dot(mO2) /(V) over dot(mO2) ratio determines the microvascular O-2 partial pressure (P-mvO2), which represents the ultimate force driving blood-myocyte O-2 flux (see Fig. 1). Improvements in perfusive and diffusive O-2 conductances are essential to support faster rates of oxidative phosphorylation (reflected as faster (V) over dot(mO2) kinetics during transitions in metabolic demand) and reduce the reliance on anaerobic glycolysis and utilization of finite energy sources (thus lowering the magnitude of the O2 deficit) in trained CHF muscle. These adaptations contribute to attenuated muscle metabolic perturbations (e.g., changes in [PCr], [Cr], [ADP], and pH) and improved physical capacity (i.e., elevated critical power and maximal (V) over dot(mO2)). Preservation of such plasticity in response to exercise training is crucial considering the dominant role of skeletal muscle dysfunction in the pathophysiology and increased morbidity/mortality of the CHF patient. This brief review focuses on the mechanistic bases for improved (Q) over dot(mO2) /(V) over dot(mO2) matching (and enhanced P-mvO2) with exercise training in CHF with both preserved and reduced ejection fraction (HFpEF and HFrEF, respectively). Specifically, O-2 convection within the skeletal muscle microcirculation, O-2 diffusion from the red blood cell to the mitochondria, and muscle metabolic control are particularly susceptive to exercise training adaptations in CHF. Alternatives to traditional whole body endurance exercise training programs such as small muscle mass and inspiratory muscle training, pharmacological treatment (e.g., sildenafil and pentoxifylline), and dietary nitrate supplementation are also presented in light of their therapeutic potential. Adaptations within the skeletal muscle O-2 transport and utilization system underlie improvements in physical capacity and quality of life in CHF and thus take center stage in the therapeutic management of these patients.