This study was the first to investigate the vascular implications of contracting SARS-CoV-2 among young, otherwise healthy adults. Using a cross-sectional design, this study assessed vascular function 3–4 wk after young adults tested positive for SARS-CoV-2. The main findings from this study were a strikingly lower vascular function and a higher arterial stiffness compared with healthy controls. Together, these results suggest rampant vascular effects seen weeks after contracting SARS-CoV-2 in young adults.

 The impact of SARS-CoV-2 infection on autonomic and cardiovascular function in otherwise healthy individuals is unknown. We show for the first time that young adults recovering from SARS-CoV-2 have elevated resting sympathetic activity, but similar heart rate and blood pressure, compared with control subjects. Survivors of SARS-CoV-2 also exhibit suppressed sympathetic nerve activity and pain perception during a cold pressor test compared with healthy controls.  Further, these individuals display higher sympathetic nerve activity throughout an orthostatic challenge, as well as an exaggerated heart rate response to orthostasis. If similar autonomic dysregulation, like that found here in young individuals, is present in older adults following SARS-CoV-2 infection, there may be substantial adverse implications for cardiovascular health.

Contracting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been observed to cause decrements in vascular function of young adults. However, less is known about the impact of SARS-CoV-2 on arterial stiffness and structure, which might have additional implications for cardiovascular health. The purpose of this study was to assess the carotid artery stiffness and structure using ultrasound and the aortic augmentation index (AIx) using applanation tonometry in young adults after they tested positive for SARS-CoV-2. We hypothesized that carotid artery stiffness, carotid intima-media thickness (cIMT) and aortic AIx would be elevated in young adults with SARS-CoV-2 compared with healthy young adults. We evaluated 15 young adults (six male and nine female; 20 ± 1 years of age; body mass index, 24 ± 3 kg m −2 ) 3-4 weeks after a positive SARS-CoV-2 test result compared with young healthy adults (five male and 10 female; 23 ± 1 years of age; body mass index, 22 ± 2 kg m −2 ) who were evaluated before the coronavirus 2019 pandemic. Carotid stiffness, Young's modulus and cIMT were assessed using ultrasound, whereas aortic AIx and aortic AIx standardized to 75 beats min −1 (AIx@HR75) were assessed from carotid pulse wave analysis using SphygmoCor. Group differences were observed for carotid stiffness (control, 5 ± 1 m s −1 ; SARS-CoV-2, 6 ± 1 m s −1 ), Young's modulus (control, 396 ± 120 kPa; SARS-CoV-2, 576 ± 224 kPa), aortic AIx (control, 3 ± 13%; SARS-CoV-2, 13 ± 9%) and aortic AIx@HR75 (control, −3 ± 16%; SARS-CoV-2, 10 ± 7%; P < 0.05). However, cIMT was similar between groups (control, 0.42 ± 0.06 mm; SARS-CoV-2, 0.44 ± 0.08 mm; P > 0.05). This cross-sectional analysis revealed higher carotid artery stiffness and aortic stiffness among young adults with SARS-CoV-2.These results provide further evidence of cardiovascular impairments among young adults recovering from SARS-CoV-2 infection, which should be considered for cardiovascular complications associated with SARS-CoV-2.

Total knee arthroplasty (TKA) utilizes a tourniquet to reduce blood loss, maintain a clear surgical “bloodless” field, and to ensure proper bone-implant cementing. In 2007, over 600,000 TKAs were performed in the United States, and this number is projected to increase to 3.48 million procedures performed annually by 2030. The acute effects of tourniquet-induced ischemia-reperfusion (I/R) on human skeletal muscle cells are poorly understood and require critical investigation, as muscle atrophy following this surgery is rapid and represents the most significant clinical barrier to long-term normalization of physical function. To determine the acute effects of I/R on skeletal muscle cells, biopsies were obtained at baseline, maximal ischemia (prior to tourniquet release), and reperfusion (following tourniquet release). Quadriceps volume was determined before and 2 wk post-TKA by MRI. We measured a 36% decrease in phosphorylation of Akt Ser473during ischemia and 37% during reperfusion ( P < 0.05). 4E-BP1 Thr37/46phosphorylation decreased 29% during ischemia and 22% during reperfusion ( P < 0.05). eEF2 Thr56phosphorylation increased 25% during ischemia and 43% during reperfusion ( P < 0.05). Quadriceps volume decreased 12% in the TKA leg ( P < 0.05) and tended to decrease (6%) in the contralateral leg ( P = 0.1). These data suggest cap-dependent translation initiation, and elongation may be inhibited during and after TKA surgery. We propose that cap-dependent translational events occurring during surgery may precipitate postoperative changes in muscle cells that contribute to the etiology of muscle atrophy following TKA.

Common cyclooxygenase (COX)-inhibiting drugs enhance resistance exercise induced muscle mass and strength gains in older individuals. The purpose of this investigation was to determine whether the underlying mechanism regulating this effect was specific to Type I or Type II muscle fibers, which have different contractile and metabolic profiles. Muscle biopsies (vastus lateralis) were obtained before and after 12 weeks of knee-extensor resistance exercise (3 days/week) from healthy older men who consumed either a placebo (n = 8; 64±2 years) or COX inhibitor (acetaminophen, 4 gram/day; n = 7; 64±1 years) in double-blind fashion. Muscle samples were examined for Type I and II fiber cross-sectional area, capillarization, and metabolic enzyme activities (glycogen phosphorylase, citrate synthase, β-hydroxyacyl-CoA-dehydrogenase). Type I fiber size did not change with training in the placebo group (304±590 μm(2)) but increased 28% in the COX inhibitor group (1,388±760 μm(2), p < .1). Type II fiber size increased 26% in the placebo group (1,432±499 μm(2), p < .05) and 37% in the COX inhibitor group (1,825±400 μm(2), p < .05). Muscle capillarization and enzyme activity were generally maintained in the placebo group. However, capillary to fiber ratio increased 24% (p < .1) and citrate synthase activity increased 18% (p < .05) in the COX inhibitor group. COX inhibitor consumption during resistance exercise in older individuals enhances myocellular growth, and this effect is more pronounced in Type I muscle fibers.

Although aspirin is one of the most common anti-inflammatory drugs in the world, the effect of aspirin on human skeletal muscle inflammation is almost completely unknown. This study examined the potential effects and related time course of an orally consumed aspirin dose on the inflammatory prostaglandin E (PGE)/cyclooxygenase (COX) pathway in human skeletal muscle. Skeletal muscle biopsies were taken from the vastus lateralis of 10 healthy adults (5 male and 5 female, 25 ± 2 yr old) before (Pre) and 2, 4, and 24 h after (Post) a standard dose (975mg) of aspirin and partitioned for analysis of 1) in vivo PGE levels in resting skeletal muscle and 2) ex vivo skeletal muscle PGE production when stimulated with the COX substrate arachidonic acid (5 μM). PGE levels in vivo and PGE production ex vivo were generally unchanged at each time point after aspirin consumption. However, most individuals clearly showed suppression of PGE, but at varying time points after aspirin consumption. When the maximum suppression after aspirin consumption was examined for each individual, independent of time, PGE levels in vivo (184 ± 17 and 104 ± 23pg/g wet wt at Pre and Post, respectively) and PGE production ex vivo (2.74 ± 0.17 and 2.09 ± 0.11pg·mg wet wt·min at Pre and Post, respectively) were reduced ( P < 0.05) by 44% and 24%, respectively. These results provide evidence that orally consumed aspirin can inhibit the COX pathway and reduce the inflammatory mediator PGE in human skeletal muscle. Findings from this study highlight the need to expand our knowledge regarding the potential role for aspirin regulation of the deleterious influence of inflammation on skeletal muscle health in aging and exercising individuals. NEW & NOTEWORTHY This study demonstrated that orally consumed aspirin can target the prostaglandin/cyclooxygenase pathway in human skeletal muscle. This pathway has been shown to regulate skeletal muscle metabolism and inflammation in aging and exercising individuals. Given the prevalence of aspirin consumption, these findings may have implications for skeletal muscle health in a large segment of the population.

 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.