Impaired Post‐Occlusive Reoxygenation and Reperfusion in the Lower Legs of PAD Patients
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 atherosclerotic vascular disease that leads to demand ischemia and impaired mitochondrial function in the lower legs. Identifying the extent of non‐exercise related convective and diffusive oxygen transport impairments is important in furthering our understanding of microvascular impairments in this population.PurposeThe aim of this study was to determine the extent of reperfusion and reoxygenation impairments in the medial gastrocnemius (MG) and soleus (SOL) muscles of PAD patients.MethodsA novel functional MRI (fMRI) sequence was employed to simultaneously assess tissue perfusion, T2* relaxation time (used as an index of tissue oxygenation), and venous oxygen saturation (SvO2) in 3 patients with symptomatic PAD and 3 healthy age‐matched controls. Collecting these three parameters in a single scan was achieved by interleaving a gradient‐recalled‐echo (GRE) sequence into the post‐labeling‐delay of a pulsed‐arterial‐spin‐labeling sequence (total acquisition time of about 3.2 seconds). FMRI data were continuously collected during a reactive hyperemia protocol that consisted of a 2‐minute baseline, a 5‐minute period of occlusion, and a 5‐minute period of reactive hyperemia. Occlusion pressures ranged between 185 mmHg and 200 mmHg as tolerated by the subjects. Complete occlusion was verified in all subjects. Region of interest analyses were performed on the MG and SOL muscles of each subject. Perfusion and T2* were first converted to a delta score (AU), and then analyzed for peak responses (relative to baseline), time‐to‐peak (TTP, relative to end‐occlusion), and the slope of recovery. SvO2, expressed as a percentage of oxygen (%), responds in a biphasic pattern to reactive hyperemia. Specifically, SvO2 initially decreases (termed “washout”) upon cuff release, followed by a recovery that often surpasses baseline values. Accordingly, the peaks and slopes of washout and recovery are reported for SvO2. All variables were compared between groups using independent samples t‐tests.ResultsResults indicated that MG T2* TTP was longer (+40.5±11.1 seconds, t=−3.6, P=0.02), SOL peak perfusion was attenuated (−98.9±29.5 AU, t=3.3, P=0.02), and the slope of SvO2 washout was less steep in PAD patients compared to controls (−1.3±0.3, t=3.4, P=0.02). PAD patients also tended to exhibit a longer MG T2* recovery slope (0.07±0.02, t=2.6, P=0.057), and lower MG peak perfusion (−26.0±9.8 AU, t=2.6, P=0.057) compared to controls.ConclusionsThese data suggest that reperfusion and oxygenation responses to post‐occlusive reactive hyperemia are blunted and delayed in lower legs of PAD patients. More importantly, this highlights the severity of microvascular dysfunction in this population.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.