Accelerated Early Oxygen Kinetics in the Medial Gastrocnemius of PAD Patients During Light‐Intensity Plantar Flexion
Authors: Stavres Jon , Sica Chris T , Blaha Cheryl , Herr Michael , Cauffman Aimee , Pai Samuel , Kim Danielle Jin‐Kwang , Wang Jian‐Li , Yang Qing X , Sinoway Lawrence I 
Published: June 2021

Peripheral arterial disease (PAD) is a systemic vascular disease characterized by impaired skeletal muscle perfusion and mitochondrial respiration. Symptoms most often manifest during moderate‐intensity exercise, such as brisk walking. While the effect of PAD on oxygen transport after the onset of symptoms is well established, the contributions of convective and diffusive oxygen transport to early‐phase muscular work are less clear.PurposeThe aim of this study was to determine if oxygen transport kinetics are altered in the affected muscles of PAD patients during early stage, pre‐symptomatic exercise.MethodsTo answer this question, 5 patients with bilateral PAD and 5 healthy age‐matched controls performed graded dynamic plantar flexion exercise in the bore of a 3T MRI scanner. Exercise began at a workload of 2 kg and increased by 2 kg every 2 minutes for a total of 10 minutes, or until fatigue. Within each 2‐minute stage, subjects performed plantar flexion at a cadence of 30 contractions per minute for a total of 110 seconds. During the final 10 seconds of each stage, a custom fMRI sequence was used to simultaneously examine perfusion, T2* relaxation time (an index of tissue oxygenation), and venous oxygen saturation (SvO2) in the medial gastrocnemius. This imaging protocol consisted of a gradient‐recalled‐echo sequence interleaved into the post labeling delay of a pulsed‐arterial‐spin‐labeling sequence (acquisition time=3.2 seconds). Heart rate and blood pressure were also collected during the final minute of each stage using an automated MRI‐compatible brachial blood pressure cuff.ResultsAs has been reported elsewhere, the peak mean arterial pressure response was augmented in PAD patients (+14.34 mmHg, P=0.03). For fMRI data, multi‐factorial analyses of variance with repeated measures indicated significant group by time interactions for perfusion (F(1,8)=10.671, P=0.01) and T2* relaxation time (F(1,8)=5.285, P=0.05). After eliminating a matched‐pair due to the presence of an outlier, results also indicated a trend towards a significant group by time interaction for SvO2 (F(1,6)=5.629, P=0.055). These interactions can be explained by an initial attenuation in T2* in the PAD group compared to controls at 2 kg (mean diff=1.6±0.7 AU, P=0.05); which was followed by a significant increase in perfusion at 4 kg in the PAD group but not controls (mean diff=17.8±5.4 AU, P=0.01). SvO2 also tended to be lower at 4 kg in the PAD group compared to the control group (mean diff=13.2±5.5%, respectively, P=0.055).ConclusionsOur results indicate that oxygen transport kinetics are accelerated during the early phases of pre‐symptomatic plantar flexion exercise in PAD patients. We postulate that this may be a compensatory mechanism to the reduced total perfusion and mitochondrial capacity previously reported in PAD patients, and may also be partially mediated by the augmented pressor response to exercise.Support or Funding InformationThis research was supported NIH P01 HL134609 (PI‐Sinoway).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.