Abstract

Background and Aims: Intermittent claudication (IC) in patients with peripheral artery disease (PAD) is thought to be caused by reduced lower extremity macrovascular blood flow. However, the ankle-brachial index (ABI) (a macrovascular measure) does not correlate well with patient-reported outcome measures. We aimed to study microvascular and metabolic skeletal muscle responses to exercise in patients with IC using positron emission tomography (PET). Methods: We enrolled 19 patients with IC (ABI < 0.90 and imaging/angiographic evidence of PAD) and 12 healthy controls (HCs) (normal ABI). All subjects underwent rest perfusion imaging of the legs with 13 N-ammonia or 11 C-acetate PET followed by a graded treadmill test. Subjects exercised until limited by claudication or the end of the 20-minute protocol. Subjects then underwent immediately post-exercise PET imaging of the legs. Skeletal muscle blood flow (SMBF) was quantified in each leg at rest and immediately post-exercise. Skeletal muscle oxygen utilization (SMVO 2 ) normalized to SMBF was also quantified for patients who underwent imaging with 11 C-acetate. Peripheral artery questionnaire (PAQ) summary score was obtained for all subjects. Results: We found that SMBF was increased post-exercise in all subjects, and stress/rest SMBF was higher in the legs of subjects with PAD than in the legs of HCs ( Figure 1A ). We also found that stress SMVO 2 /SMBF was higher in legs of patients with PAD than in the legs of HCs ( Figure 1B ). There was a moderate, significant correlation between limb stress/rest SMBF and PAQ score ( Figure 1C ) and a strong, significant correlation between limb stress SMVO 2 /SMBF and PAQ score ( Figure 1D ). Conclusions: In conclusion, we found that SMBF increased in all subjects after treadmill exercise and paradoxically to the greatest degree in patients with IC. We also found that PET-derived markers of post-exercise microvascular perfusion and metabolism correlated with patient-reported outcomes.

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