Acute and chronic adaptations to intermittent pnemuatic [sic] leg compressions

Abstract

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT REQUEST OF AUTHOR.] Few therapies exist that improve functional capacity and quality of life of patients with peripheral arterial disease (PAD). Despite the growing prevalence of this highly debilitating condition in the aging population, the currently available treatment options have a markedly low cost-effectiveness and accessibility. Application of intermittent pneumatic leg compressions (IPC) is emerging as a promising strategy for PAD but the mechanistic basis of action of this approach remains largely unknown. The studies described in this dissertation were designed to gain insights into the acute adjustments and long-term adaptations to IPC application. To accomplish these aims we developed a model in rodents that allowed us to study in depth the essential physiological responses to this therapy in healthy animals and in a preclinical model of peripheral arterial insufficiency. We conducted studies to investigate: 1) the impact of a single session of IPC on limb hemodynamics and skeletal muscle gene expression (Chapters 2 and 3) and 2) the long-term consequences of IPC on exercise tolerance, muscle blood flow, capillarization and oxidative capacity (Chapter 4). We also report the findings of our initial efforts to translate our findings in rodents to humans by studying the chronic effects on forearm compression on blood flow in healthy young subjects (Appendix). Collectively, these studies shed new light on the therapeutic potential of IPC for patients with PAD as well as on the possible mechanisms underlying the clinical benefits associated with this novel therapy.