Ischemic Preconditioning Acutely Improves Functional Sympatholysis during Handgrip Exercise in Healthy Males but not Females

Abstract

ABSTRACT Purpose Ischemic preconditioning (IPC), a procedure that involves the cyclic induction of limb ischemia and reperfusion via tourniquet inflation, has been reported to improve exercise capacity and performance, but the underlying mechanisms remain unclear. During exercise, sympathetically mediated vasoconstriction is dampened in active skeletal muscle. This phenomenon, termed functional sympatholysis, plays a critical role in maintaining oxygen delivery to working skeletal muscle and may contribute to determining exercise capacity. Herein, we investigate the effects of IPC on functional sympatholysis in humans. Methods In 20 (10M/10F) healthy young adults, forearm blood flow (Doppler ultrasound) and beat-to-beat arterial pressure (finger photoplethysmography) were measured during lower body negative pressure (LBNP; −20 mm Hg) applied at rest and simultaneously during rhythmic handgrip exercise (30% maximum contraction) before and after local IPC (4 × 5-min 220 mm Hg) or sham (4 × 5-min 20 mm Hg). Forearm vascular conductance (FVC) was calculated as forearm blood flow/mean arterial pressure and the magnitude of sympatholysis as the difference of LBNP-induced changes in FVC between handgrip and rest. Results At baseline, LBNP decreased FVC (females [F] = ∆–41% ± 19%; males [M] = ∆–44% ± 10%), and these responses were attenuated during handgrip (F = ∆–8% ± 9%; M = ∆–8% ± 7%). After IPC, LBNP induced similar decreases in resting FVC (F = ∆–37% ± 19%; M = ∆–44% ± 13%). However, during handgrip, this response was further attenuated in males (∆–3% ± 9%, P = 0.02 vs pre) but not females (∆–5% ± 10%, P = 0.13 vs pre), which aligned with an IPC-mediated increase in sympatholysis (M-pre = 36% ± 10% vs post = 40% ± 9%, P = 0.01; F-pre = 32% ± 15% vs post = 32% ± 14%, P = 0.82). Sham IPC had no effect on any variables. Conclusions These findings highlight a sex-specific effect of IPC on functional sympatholysis and provide evidence of a potential mechanism underlying the beneficial effects of IPC on human exercise performance.