Post-walking exercise skeletal muscle perfusion and energetics in patients with symptomatic lower extremity peripheral artery disease

• Published in: Journal of nuclear cardiology Vol. 46; p. 102143
• Main Authors: Divakaran, Sanjay, Harms, Hendrik J., Robertson, Matthew, Merugumala, Sai K., Park, Mi-Ae, Kijewski, Marie F., Martell, Laurel B., Morgan, Victoria, Barrett, Leanne, Perillo, Anna, Yang, David, Jarolim, Petr, Feinberg, Mark W., Gerhard-Herman, Marie D., Belkin, Michael, Lin, Alexander P., Creager, Mark A., Bonaca, Marc P., Di Carli, Marcelo F.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2025
• Subjects: Aged; Claudication; Exercise Test; Female; Humans; Intermittent Claudication - diagnostic imaging; Intermittent Claudication - physiopathology; Lower Extremity - blood supply; Magnetic Resonance Spectroscopy; Male; Microvascular disease; Middle Aged; Muscle, Skeletal - blood supply; Muscle, Skeletal - diagnostic imaging; Muscle, Skeletal - metabolism; Muscle, Skeletal - physiopathology; Peripheral Arterial Disease - diagnostic imaging; Peripheral Arterial Disease - metabolism; Peripheral Arterial Disease - physiopathology; Peripheral artery disease; Phosphocreatine - metabolism; Positron Emission Tomography Computed Tomography; Prospective Studies; Skeletal muscle metabolism; Skeletal muscle perfusion; Walking - physiology; Peripheral artery disease; Claudication; Skeletal muscle perfusion; Microvascular disease; Skeletal muscle metabolism
• ISSN: 1071-3581; 1532-6551; 1532-6551
• DOI: 10.1016/j.nuclcard.2025.102143

The pathophysiology of symptoms and reduced exercise capacity from peripheral artery disease (PAD) remains unclear. Additionally, there is limited information on blood flow and skeletal muscle energetics after walking exercise in patients with claudication in comparison to healthy individuals. We prospectively enrolled 19 patients with claudication from PAD and 12 healthy subjects. All participants underwent rest and post-exercise perfusion imaging of the lower leg muscles via PET/CT. Participants exercised on a treadmill following the Gardner-Skinner protocol. Skeletal muscle blood flow (SMBF) was quantified in each leg at rest and immediately after exercise. Phosphocreatine (PCr) recovery and NAD+/NADH concentrations were measured pre- and post-exercise by 31P magnetic resonance spectroscopy (MRS) in a subset of participants. Comparisons were made between the legs of healthy subjects and the asymptomatic and symptomatic legs of patients with PAD. SMBF increased post-exercise in all participants. Among patients with PAD, the post-exercise/rest SMBF ratio, was higher in the symptomatic (n = 25) than asymptomatic (n = 13) legs (8.03 ± 2.84 vs 6.03 ± 2.81, P = 0.046) and higher than the post-exercise/rest SMBF ratio measured in the legs of healthy subjects (4.40 ± 1.47, P < 0.001). The post-exercise/rest PCr and NAD+/NADH ratios were lower in the legs of patients with PAD (n = 3) when compared with the legs of healthy subjects (n = 6) (0.79 ± 0.06 vs 1.00 ± 0.07 (P = 0.004) and 1.15 ± 0.43 vs 2.08 ± 0.30 (P = 0.007), respectively). SMBF increased post-exercise to the greatest degree in the symptomatic legs of patients with PAD and post-exercise skeletal muscle mitochondrial function was abnormal in patients with PAD. These data suggest that the causes of symptoms and reduced exercise capacity from PAD are not limited to abnormal perfusion pressure in the legs. [Display omitted]