Respiratory and limb muscle dysfunction in pulmonary arterial hypertension: a role for exercise training?

Abstract

Respiratory and limb muscle dysfunction is emerging as an important pathophysiological abnormality in pulmonary arterial hypertension (PAH). Muscle abnormalities appear to occur frequently and promote dyspnea, fatigue, and exercise limitation in patients with PAH. Preliminary data suggest that targeted muscle training may be of benefit, although further evidence is required to consolidate these findings into specific recommendations for exercise training in patients with PAH. This article reviews the current evidence on prevalence, risk factors, and implications of respiratory and limb muscle dysfunction in patients with PAH. It also reviews the impact of exercise rehabilitation on morphologic, metabolic, and functional muscle profile and outcomes in PAH. Future research priorities are highlighted.

Keywords: pulmonary arterial hypertension; rehabilitation; respiratory muscles; skeletal muscle.

Figures

Figure 1

Conceptual model of the factors and mechanisms that lead to muscle dysfunction in pulmonary arterial hypertension and their implications. SNA: sympathetic nerve activity.

Figure 2

The muscle hypothesis. Muscle work and accumulation of products of muscle metabolism during exercise lead to augmented chemoreceptor gain and ergoreceptor drive in the impaired skeletal musculature. This leads to enhanced transmission to the CNS through sensitive, afferent unmyelinated nerve fibers. The CNS responds with increased sympathetic efferent discharge to the peripheral muscles (MSNA), which causes vasoconstriction and limitation of blood flow and oxygen transportation to the exercising skeletal muscles, thus promoting fatigue and premature cessation of exercise. Finally, enhanced sympathetic drive promotes hyperventilation and breathlessness. MSNA: muscle sympathetic nerve activity; CNS: central nervous system.

Figure 3

Potential impact of exercise training in patients with pulmonary arterial hypertension.