The exercise pressor reflex and active O2 transport in peripheral arterial disease.

Jon Stavres,Christopher T Sica,Michael Herr,Qing X Yang,Lawrence I Sinoway,Aimee Cauffman,Jianli Wang,Jeffrey Vesek,Samuel Pai,Cheryl Blaha

doi:10.14814/phy2.14243

Abstract

It is unclear if the exaggerated exercise pressor reflex observed in peripheral arterial disease (PAD) patients facilitates Oxygen (O2) transport during presymptomatic exercise. Accordingly, this study compared O2 transport between PAD patients and healthy controls during graded presymptomatic work. Seven PAD patients and seven healthy controls performed dynamic plantar flexion in the bore of a 3T MRI scanner. Perfusion, T2* (an index of relative tissue oxygenation), and SvO2 (a measure of venous oxygen saturation) were collected from the medial gastrocnemius (MG) during the final 10 seconds of each stage. Blood pressure was also collected during the final minute of each stage. As expected, the pressor response to presymptomatic work (4 kg) was exaggerated in PAD patients compared to controls (+14 mmHg ± 4 and +7 mmHg ± 2, P ≤ 0.034). When normalized to changes in free water content (S0), T2* was lower at 2 kg in PAD patients compared to controls (−0.91 Δms/ΔAU ± 0.3 and 0.57 Δms/ΔAU ± 0.3, P ≤ 0.008); followed by a greater increase in perfusion at 4 kg in the PAD group (+18.8 mL/min/100g ± 6.2 vs. −0.21 mL/min/100g ± 3.2 in PAD and controls, P ≤ 0.026). Lastly, SvO2 decreased at 4 kg in both groups (−13% ± 4 and −2% ± 4 in PAD and controls, P ≤ 0.049), suggesting an increase in O2 extraction in the PAD group. Based on these findings, O2 transport appears to be augmented during graded presymptomatic work in PAD patients, and this may be partially mediated by an exaggerated pressor response.

Highlights

Peripheral arterial disease (PAD) is a systemic vascular disease affecting approximately 8.5 million people in the United States and 200 million people worldwide (Roger et al, 2011; Shu and Santulli, 2018)
Exercise required more perceived effort and elicited a higher pain response in PAD patients compared to healthy controls (Table 1)
systolic blood pressure (SBP) (F2,24 = 5.10, P = 0.014) and mean arterial pressure (MAP) (F2,24 = 4.36, P = 0.024) both increased more at the 4 kg workload in PAD patients compared to controls (DMAP = +14 mmHg Æ 4 and + 7 mmHg Æ 2 [Fig. 2A] and ΔSBP = +23 mmHg Æ 5 and +9 mmHg Æ 2 in PAD and CON, respectively, all P ≤ 0.034)

Summary

Introduction

Peripheral arterial disease (PAD) is a systemic vascular disease affecting approximately 8.5 million people in the United States and 200 million people worldwide (Roger et al, 2011; Shu and Santulli, 2018). While regular exercise has been shown to improve PAD symptoms (Gardner et al, 2000), impaired O2 delivery limits exercise tolerance. This leads to a “vicious cycle,” where decreased levels of activity accelerate disease progression. It is well established that convective O2 transport is impaired in PAD patients, and more recent evidence suggests that impaired O2 utilization at the mitochondria (and diffusive O2 transport) may contribute to the pathophysiology of PAD (Pipinos et al, 2003; AlGhatrif et al, 2017; Schmidt et al, 2017) This introduces some uncertainty regarding the sequence of disease progression;

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