Impact of supervised exercise on skeletal muscle blood flow and vascular function measured with MRI in patients with peripheral artery disease

Abstract

Supervised exercise is a common therapeutic intervention for patients with peripheral artery disease (PAD), however, the mechanism underlying the improvement in claudication symptomatology is not completely understood. The hypothesis that exercise improves microvascular blood flow is herein tested via temporally resolved magnetic resonance imaging (MRI) measurement of blood flow and oxygenation dynamics during reactive hyperemia in the leg with the lower ankle-brachial index. One hundred and forty-eight subjects with PAD were prospectively assigned to standard medical care or 3 mo of supervised exercise therapy. Before and after the intervention period, subjects performed a graded treadmill walking test, and MRI data were collected with Perfusion, Intravascular Venous Oxygen saturation, and T₂* (PIVOT), a method that simultaneously quantifies microvascular perfusion, as well as relative oxygenation changes in skeletal muscle and venous oxygen saturation in a large draining vein. The 3-mo exercise intervention was associated with an improvement in peak walking time (64% greater in those randomized to the exercise group at follow-up, P < 0.001). Significant differences were not observed in the MRI measures between the subjects randomized to exercise therapy versus standard medical care based on an intention-to-treat analysis. However, the peak postischemia perfusion averaged across the leg between baseline and follow-up visits increased by 10% (P = 0.021) in participants that were adherent to the exercise protocol (completed >80% of prescribed exercise visits). In this cohort of adherent exercisers, there was no difference in the time to peak perfusion or oxygenation metrics, suggesting that there was no improvement in microvascular function nor changes in tissue metabolism in response to the 3-mo exercise intervention.NEW & NOTEWORTHY Supervised exercise interventions can improve symptomatology in patients with peripheral artery disease, but the underlying mechanism remains unclear. Here, MRI was used to evaluate perfusion, relative tissue oxygenation, and venous oxygen saturation in response to cuff-induced ischemia. Reactive hyperemia responses were measured before and after 3 mo of randomized supervised exercise therapy or standard medical care. Those participants who were adherent to the exercise regimen had a significant improvement in peak perfusion.

Keywords: exercise therapy; magnetic resonance imaging; microcirculation; peripheral artery disease; vascular function.

Figure 1.

Experimental overview. Subjects were assessed for eligibility at a screening visit, comprising bilateral ABI measurement and Gardner–Skinner treadmill test and completed a Medical Outcome Scales Health Survey (SF-36). Within 1 mo, eligible subjects returned for their baseline test visit. Subjects were then randomized to supervised exercise therapy or standard medical care and returned for the follow-up visit ∼3 mo later. ABI, ankle-brachial index; MRI, magnetic resonance imaging.

Figure 2.

Magnitude images (A and C), schematic of slice locations (B), parametric maps (D–F), and time courses (G–I) from a representative subject (ABI = 0.81). Parametric maps are shown during the peak hyperemic response for perfusion (D), MRI phase [related to $\mathrm{S}{\mathrm{V}}_{{\text{O}}_2}$; E, posterior tibial (arrows) and peroneal (arrowheads) veins], and T₂* (F, soleus ROI, shown in black). Dotted line in H represents unreliable $\mathrm{S}{\mathrm{V}}_{{\text{O}}_2}$ data because of motion during cuff inflation. ABI, ankle-brachial index; HbO₂, oxyhemoglobin; MRI, magnetic resonance imaging; ROI, region of interest; $\mathrm{S}{\mathrm{V}}_{{\text{O}}_2}$, venous oxygen saturation; T₂*, MRI parameter related to microvascular oxygen content.

Figure 3.

Consort diagram showing patient recruitment and attrition. ABI, ankle-brachial index; MRI, magnetic resonance imaging.