 What is the central question of this study?This study sought to investigate whether central and peripheral hemodynamics during handgrip exercise were different in young adults 3-4 weeks following infection with of SARS-CoV-2 compared with young healthy adults. What is the main finding and its importance?The main findings are that exercising heart rate was higher while brachial artery blood flow and vascular conductance were lower in the SARS-CoV-2 compared with the control group. These findings provide evidence for peripheral impairments to exercise among adults with SARS-CoV-2, which may contribute to exercise limitations.

Background One of the many unique features of heart failure with preserved ejection fraction (HFpEF) is the presence of multiple comorbidities, many of which are characterized by a pro‐inflammatory and pro‐oxidant state which may impair vascular function. This axis of inflammation, oxidative stress, and vascular function has been well described in other patient populations, whereby increases in reactive oxygen species lead to eNOS uncoupling, reduced nitric oxide (NO) bioavailability, and ultimately, impaired endothelium‐dependent vasodilation. Though there are many potential strategies for combating the damaging effects of inflammation and oxidative stress on peripheral vascular function, antioxidant (AO) administration has emerged as a simple, but effective, approach. However, no studies to date have evaluated the efficacy of AO administration to target peripheral vascular inflammation and dysfunction in patients with HFpEF. Purpose The present study sought to evaluate the efficacy of an over‐the‐counter antioxidant (AO) cocktail (600mg alpha lipoic acid, 1,000mg vitamin C, and 600IU vitamin E) to acutely mitigate inflammation and oxidative stress, and subsequently improve vascular function, in patients with HFpEF. Methods Flow mediated dilation (FMD) and reactive hyperemia (RH) were evaluated to assess conduit vessel and microvascular function, respectively, following administration of either placebo (PL) or AO in 16 HFpEF patients (73±10yrs) using a double‐blind, crossover design. Circulating biomarkers of inflammation (C‐reactive protein, CRP), oxidative stress (Malondialdehyde and Protein Carbonyl), free radical concentration (EPR Spectroscopy), antioxidant capacity, and nitric oxide (NO) bioavailability (plasma nitrate, NO3− and nitrite, NO2−) were also assessed. Results FMD improved following AO administration (PL: 3.49 ± 0.7%, AO: 5.83 ± 1.0%), while RH responses were similar between conditions (PL: 428 ± 51ml, AO: 425 ± 51ml). AO administration decreased CRP (PL: 4429 ± 705ng/ml, AO: 3664 ± 520ng/ml) and increased NO2− (PL: 182 ± 21nM, AO: 213 ± 24nM), but did not affect other biomarkers. Conclusions This study has identified the efficacy of an acute, over‐the‐counter dose of vitamins C, E, and alpha lipoic acid to mitigate vascular inflammation and improve conduit artery endothelium‐dependent vasodilation in patients with HFpEF, providing new insight into the mechanisms that govern peripheral vascular dysfunction in this patient group. Support or Funding Information Funded in part by the National Institutes of Health (HL118313) and the U.S. Department of Veterans Affairs (RX001311, RX001697, CX001183). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The PARADIGM-HF trial identified a marked reduction in the risk of death and hospitalization for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) treated with sacubitril-valsartan, but the physiologic processes underpinning these improvements are unclear. We tested the hypothesis that treatment with sacubitril-valsartan improves peripheral vascular function, functional capacity, and inflammation in patients with HFrEF. We prospectively studied patients with HFrEF (n=11, 10M/1F, left ventricular ejection fraction 27±8%) on optimal, guideline-directed medical treatment who were subsequently prescribed sacubitril-valsartan (open-label, uncontrolled, and unblinded). Peripheral vascular function (brachial artery flow-mediated dilation (FMD, conduit vessel function) and reactive hyperemia (RH, microvascular function)), functional capacity (six-minute walk test (6MWT) distance), and the pro-inflammatory biomarkers, tumor necrosis factor-alpha (TNF-α) and interleukin-18 (IL-18) were obtained at baseline and again at 1, 2, and 3 months of treatment. %FMD improved after 1 month of treatment, and this favorable response persisted for months 2 and 3 (baseline: 3.25±1.75%; 1mo: 5.23±2.36%; 2mo: 5.81±1.79%; 3mo: 6.35±2.77%), while RH remained unchanged. 6MWT distance increased at months 2 and 3 (baseline: 420±92 m; 1mo: 436±98 m; 2mo: 465±115 m; 3mo: 460±110 m), and there was a sustained reduction in TNF-α (baseline: 2.38±1.35 pg/mL; 1mo: 2.06±1.52 pg/mL; 2mo: 1.95±1.34 pg/mL; 3mo: 1.92±1.37 pg/mL) and a reduction in IL-18 at months 3 (baseline: 654±150 pg/mL; 1mo: 595±140 pg/mL; 2mo: 601±176 pg/mL; 3mo: 571±127 pg/mL). This study provides new evidence for the potential of this new drug class to improve conduit vessel function, functional capacity, and inflammation in patients with HFrEF.

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Heart failure with reduced ejection fraction (HFrEF) is characterized by macrovascular dysfunction and elevated oxidative stress that may be mitigated by antioxidant (AOx) administration. In this prospective study, we assessed flow-mediated dilatation (FMD) and reactive hyperaemia responses in 14 healthy, older control participants and 14 patients with HFrEF, followed by 30 days of oral AOx administration (1 g vitamin C, 600 I.U. vitamin E and 0.6 g α-lipoic acid) in the patient group. Blood biomarkers of oxidative stress (malondialdehyde) and AOx capacity (ferric reducing ability of plasma) were also assessed. Patients with HFrEF had a lower %FMD (2.63 ± 1.57%) than control participants (5.62 ± 2.60%), and AOx administration improved %FMD in patients with HFrEF (30 days, 4.90 ± 2.38%), effectively restoring macrovascular function to that of control participants. In a subset of patients, we observed a progressive improvement in %FMD across the treatment period (2.62 ± 1.62, 4.23 ± 2.69, 4.33 ± 2.24 and 4.97 ± 2.56% at days 0, 10, 20 and 30, respectively, n = 12) that was abolished 7 days after treatment cessation (2.99 ± 1.78%, n = 9). No difference in reactive hyperaemia was evident between groups or as a consequence of the AOx treatment. Ferric reducing ability of plasma levels increased (from 6.08 ± 2.80 to 6.70 ± 1.59 mM, day 0 versus 30) and malondialdehyde levels decreased (from 6.81 ± 2.80 to 6.22 ± 2.84 μM, day 0 versus 30) after treatment. These findings demonstrate the efficacy of chronic AOx administration in attenuating oxidative stress, improving AOx capacity and restoring macrovascular function in patients with HFrEF.