Leg blood flow and skeletal muscle microvascular perfusion responses to submaximal exercise in peripheral arterial disease

Abstract

Peripheral arterial disease (PAD) is characterized by stenosis and occlusion of the lower limb arteries. While leg blood flow is limited in PAD, it remains unclear whether skeletal muscle microvascular perfusion is affected. We compared whole-leg blood flow and calf muscle microvascular perfusion following cuff occlusion and submaximal leg exercise between PAD patients (n=12, 69±9 years) and healthy age-matched control participants (n=12, 68±7 years). Microvascular blood flow (microvascular volume x flow velocity) of the medial gastrocnemius muscle was measured before and immediately after: 1) 5 min of thigh-cuff occlusion; and 2) a 5-min bout of intermittent isometric plantar-flexion exercise (400N) using real-time contrast-enhanced ultrasound (CEU). Whole-leg blood flow was measured after thigh-cuff occlusion and during submaximal plantar-flexion exercise using strain-gauge plethysmography. Post-occlusion whole-leg blood flow and calf muscle microvascular perfusion were lower in PAD patients than controls, and these parameters were strongly correlated (r=0.84; p<0.01). During submaximal exercise, total whole-leg blood flow and vascular conductance were not different between groups. There were also no group differences in post-exercise calf muscle microvascular perfusion, although microvascular blood volume was higher in PAD patients than control (12.41±6.98 vs 6.34±4.98 aU; p=0.03). This study demonstrates that the impaired muscle perfusion of PAD patients during post-occlusion hyperemia is strongly correlated with disease severity, and is likely mainly determined by the limited conduit artery flow. In response to submaximal leg exercise, microvascular flow volume was elevated in PAD patients, which may reflect a compensatory mechanism to maintain muscle perfusion and oxygen delivery during recovery from exercise.

Dynamic magnetic resonance measurements of calf muscle oxygenation and energy metabolism in peripheral artery disease

“…We observed functional hyperemia in the BOLD response after exercise for at least a subset of participants in the present study. Our data are in line with some previous results that used either radioactive tracers, NIRS, T 2 *‐weighted MRI, dynamic contrast‐enhanced ultrasound imaging, or dynamic contrast‐enhanced MRI to demonstrate calf muscle hyperemia during recovery after exercise in PAD patients. The functional hyperemia and its higher amplitude we observed in the gastrocnemius muscle of most PAD patients may be indicative of elevated levels of hypoxic metabolic end products that trigger a vasodilatory blood flow adaptation during recovery from exercise‐induced tissue deoxygenation .…”

“…Our data are in line with some previous results that used either radioactive tracers, NIRS, T 2 *‐weighted MRI, dynamic contrast‐enhanced ultrasound imaging, or dynamic contrast‐enhanced MRI to demonstrate calf muscle hyperemia during recovery after exercise in PAD patients. The functional hyperemia and its higher amplitude we observed in the gastrocnemius muscle of most PAD patients may be indicative of elevated levels of hypoxic metabolic end products that trigger a vasodilatory blood flow adaptation during recovery from exercise‐induced tissue deoxygenation . In apparent contrast, reactive hyperemia after cuff‐induced occlusion and subsequent reperfusion was shown to be blunted in PAD patients compared with healthy control subjects .…”

“…The functional hyperemia and its higher amplitude we observed in the gastrocnemius muscle of most PAD patients may be indicative of elevated levels of hypoxic metabolic end products that trigger a vasodilatory blood flow adaptation during recovery from exercise‐induced tissue deoxygenation . In apparent contrast, reactive hyperemia after cuff‐induced occlusion and subsequent reperfusion was shown to be blunted in PAD patients compared with healthy control subjects . Although an ischemia–reperfusion paradigm allows for a well‐controlled stimulus that provokes a response at the maximally available vascular capacity, exercise is more relevant to the pathophysiology of intermittent claudication in PAD .…”

A systematic review of diagnostic techniques to determine tissue perfusion in patients with peripheral arterial disease

“…Three prospective studies investigated the use of CEUS in PAD, as reported in Table 1. Duerschmied et al [15], Kundi et al [14], and Meneses et al [16] published prospective cohort studies and used different types of microbubble contrast agents. These three studies…”

“…Meneses et al [16] determined whole-leg blood flow and vascular conductance in both groups sitting and when supine. Both positions showed no significant difference at rest in PAD patients versus healthy controls.…”