Perfusion-dependent modulation of muscle contractility: an alternative perspective on fatigue and blood flow

Cardiovascular adjustments during exercise are an essential part of an integrated physiological response which supports muscular work. Fatigue resistance and exercise tolerance are influenced by the matching of blood flow (perfusion) to increased metabolic demands of contracting muscles. In healthy individuals, acute reduction in muscle perfusion impairs muscle endurance (1–3), fatigue resistance (1, 4, 5), and exercise tolerance (6–8). These performance characteristics are severely impaired in patients with peripheral arterial disease, who have blunted muscle hyperemic responses (9–11). There are excellent reviews about skeletal muscle fatigue focused on intracellular (12), neural (13, 14), and cardiovascular mechanisms (15, 16), but they do not focus on effects of perfusion per se.