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Inflammation and the Cardiovascular Responses to Exercise in Patients with Peripheral Artery Disease
Author(s) -
Craig Jesse C.,
Hart Corey R.,
Layec Gwenael C.,
Kwon Oh Sung C.,
Richardson Russell S.,
Trinity Joel D.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05936
Subject(s) - medicine , inflammation , systemic inflammation , cardiology , blood flow , blood pressure , peripheral , physical exercise , endocrinology
Background Patients with peripheral artery disease (PAD) demonstrate an exaggerated exercise pressor response (EPR). Heightened inflammation critically contributes to this exaggerated EPR in animal models of PAD, however, this relationship remains largely unexplored in humans. Therefore, we tested the hypotheses that the blood pressure response to exercise would be exaggerated in patients with PAD compared to controls; and that markers of inflammation would be positively related to this response. Methods Eight patients with PAD (ABI: 0.67±0.11) and eight healthy controls (HC; ABI: 1.16±0.07) matched for age, sex, physical activity, and physical characteristics completed plantar flexion exercise at both absolute (2.7 W) and relative (40% max; PAD: 2.1±0.2 vs HC: 4.3±0.4 W, p<0.001) intensities. Popliteal artery blood flow (Flow) was measured via Doppler ultrasound and systemic mean arterial pressure (MAP) via Finapres. Resting systemic and intramuscular markers of inflammation and oxidative stress were quantified from plasma and muscle biopsies. Results The exercise‐induced ΔMAP was greater for PAD at both the absolute (PAD: 20±3 vs HC: 9±2 mmHg, p<0.01) and relative (PAD: 23±5 vs HC: 11±2 mmHg, p=0.02) exercise intensities. The ΔFlow was lower for PAD compared to HC during both absolute (PAD: 251±53 vs HC: 545±66 ml/min, p<0.01) and relative intensities (PAD: 242±61 vs HC: 595±89 ml/min, p<0.01). Inflammatory markers including plasma tumor necrosis factor alpha (TNFα: ↑134%), interleukin‐6 (IL6: ↑92%), and intramuscular IL6 (↑77%) were elevated in PAD compared to HC (p<0.05). Additionally, markers of oxidative stress including intramuscular protein carbonyls (PC: ↑57%) and 4‐hydroxynonenal (HNE: ↑80%) were elevated in PAD (p<0.05). TNFα, plasma IL6, and PC were positively correlated with ΔMAP (r: 0.57–0.82, all p<0.05) while plasma and intramuscular IL6, PC, and HNE were negatively correlated with ΔFlow (r: 0.64–0.78, all p<0.05). Conclusions The present findings indicate an association between markers of inflammation with the cardiovascular responses to exercise in humans with PAD. Specifically, heightened inflammation and oxidative stress appear to contribute to the exaggeration the exercise pressor reflex and attenuated blood flow response during lower limb exercise in PAD. Therapeutically, targeting systemic and local inflammation may be a viable option to improve the blood pressure and blood flow responses to exercise in patients with PAD.