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Skeletal Muscle Microvascular Blood Flow as a Potential Treatment Target for Exercise Intolerance in Patients with Peripheral Arterial Disease
Dissertation   Open access

Skeletal Muscle Microvascular Blood Flow as a Potential Treatment Target for Exercise Intolerance in Patients with Peripheral Arterial Disease

Annelise L Meneses
University of the Sunshine Coast, Queensland
Doctor of Philosophy, University of the Sunshine Coast, Queensland
2020
DOI:
https://doi.org/10.25907/00053
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Skeletal Muscle Microvascular Blood Flow as a Potential Treatment Target for Exercise Intolerance in Patients with Peripheral Arterial Disease5.00 MBDownloadView
Thesis Open Access

Abstract

Peripheral arterial disease skeletal muscle microcirculation reactive hyperaemia exercise contrast-enhanced ultrasound
Peripheral arterial disease (PAD) is an atherosclerotic disease characterised by stenosis or occlusion of the arteries supplying the lower limbs. PAD is associated with severe exercise intolerance, which cannot be fully explained by the limitation in conduit artery blood flow. PAD also leads to chronic changes in the skeletal muscle phenotype, including alterations in skeletal muscle capillary density and ultrastructure, which are positively related to exercise intolerance. However, the extent to which calf muscle microvascular blood flow (i.e. perfusion) is affected by PAD is largely unknown. Using contrast-enhanced ultrasound (CEU), studies have shown a reduction in peak muscle perfusion capacity in response to ischemic provocation tests, such as thigh cuff occlusion and pain-limiting leg exercise in PAD compared with control participants. However, these studies were generally limited by the fact that they did not match PAD and control participants for age, and have not considered whole-leg or conduit artery blood flow responses when interpreting muscle microvascular responses to ischaemic provocation tests, such as cuff occlusion or exercise. Because age differences between groups may potentially bias the disease-related differences in muscle perfusion, this thesis first investigated the effect of age (Study One) and then, the effect of PAD (Study Two) on skeletal muscle microvascular perfusion responses to cuff occlusion and steady-state submaximal leg exercise using CEU. To further explore the influence of macrovascular (whole-limb) blood on muscle microvascular perfusion, this thesis investigated the effect of restored conduit artery flow, through lower-limb revascularisation, on microvascular perfusion in patients with PAD (Study Three). Last, a systematic review (Study Four) of the adjunct benefits of exercise therapy following revascularisation in patients with PAD was conducted. This review aimed to clarify whether the effect of this combined therapy approach, which has the potential to induce microvascular adaptations, is superior to revascularisation or exercise training alone.

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