Content, Virginia G.

PURPOSE: Human cutaneous circulation is used as an in vivo bioassay to examine mechanisms of systemic vascular dysfunction in cohorts of patients with accelerated cardiovascular disease risk. Local drug infusions, including atorvastatin (statin; LOX inhibitor) and systemic interventions to investigate anti-inflammatory mechanisms (e.g., oral salsalate) have been used to elucidate mechanisms underlying microvascular dysfunction. However, in healthy cohorts, high antioxidant load can attenuate total vasodilation and nitric oxide (NO)-dependent vasodilation. Thus, we aimed to examine endothelial function during high antioxidant load from these localized and systemic treatments in healthy control groups. We hypothesized that combined localized and systemic treatments will attenuate endothelial function in healthy women. METHODS: In a randomized placebo control design, oral salsalate (1500mg/twice daily/5 days) was used to assess the impact of systemic inflammation on cutaneous vascular function. Four intradermal microdialysis fibers were placed into the intradermal space of the ventral forearm of six healthy women (32±7 years). Laser-Doppler flowmeter probes, used to measure cutaneous blood flow, were placed in local heating units set to 33°C. Increasing concentrations of acetylcholine (ACh; endothelium-dependent vasodilator) from 10-10 to 10-1 M were co-perfused with one of the following: Lactated Ringer’s (control), 0.02 mM statin, 15 mM NG-nitro-L-arginine methyl ester (L-NAME; nitric oxide synthase inhibitor), and statin + L-NAME (COMBO) sequentially for 5 min each. Following the dose-response protocol, maximal cutaneous vasodilation was induced by increasing local skin temperature to 43°C and perfusing 28 mM sodium nitroprusside. Cutaneous vascular conductance (CVC) was calculated as the quotient of red blood cell flux and mean arterial pressure and normalized as a percentage of the site-specific maximum (%CVCmax). Data at each intervention were compared with control using a two-way (dose x site) analysis of variance. Responses at each dosage were compared using paired t-tests and corrected for multiple comparisons. RESULTS: Following oral salsalate, there was no difference in the %CVCmax response to ACh with local L-NAME (p=0.896) or COMBO interventions (p=0.617) as compared to the placebo. However, following oral salsalate, there was a significant reduction in %CVCmax in the statin treated site at higher ACh concentrations (10-5 M, 10-4 M, 10-3 M; all p<0.01). CONCLUSION: Endothelial function was attenuated when subjects were introduced to a combination of oral salsalate and statin localized treatments. Five-day oral salsalate intake and local statin may result in high antioxidant load in healthy women creating a shift in redox balance, thus leading to impaired endothelial function. Supported by NIH Grant R01 HL161000 This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Introduction: High intensity interval training (HIIT) during early outpatient cardiac rehabilitation (CR) improves peak oxygen uptake (VO 2 ) and reduces mortality in patients with cardiovascular disease. In a CR setting, prescribing interval intensity using rating of perceived exertion (RPE) is more feasible than using percent of VO 2peak . Additionally, prescribing HIIT with RPE may allow for progressive changes in the VO 2 response throughout a single HIIT session. However, the acute cardiopulmonary responses during individual intervals of HIIT prescribed via RPE in CR are unknown. Hypothesis: We hypothesized that VO 2peak would increase and time-to-peak (TTP) would shorten across high-intensity intervals during a single HITT session prescribed with RPE. Methods: Patients with CAD (N=14; 2 women; 56±9 yrs; 30.46±4.7 kg/m 2 ) referred to CR after an acute coronary event completed a minimum of 25 supervised HIIT sessions during which VO 2 was measured continuously. Each HIIT session included 5 or more (6±1 sessions) 1-minute high intensity intervals (target RPE: 15-17) separated by a 3 to 5-minute low intensity interval (target RPE: <12). The first and last HIIT sessions were used for analysis. VO 2peak was defined as the highest 3-breath averaged VO 2 during or up to 1 minute following each high intensity interval. Results: RPE was 15±2 and 11±2 during the high and low intensity intervals, respectively. Compared to the first HIIT session, VO 2peak was greater during the high intensity intervals of the last HIIT session (25.4±1.5 vs. 21.8±1.1 mL/kg/min; p=0.04). During the first and last HIIT sessions, VO 2peak increased across high intensity intervals (p<0.001). Although TTP was not significantly reduced across intervals during the first HIIT session (p=0.14), TTP was reduced across intervals during the last HIIT session (first interval: 67±19 vs. last interval: 58±9 s; p<0.01). Conclusions: Prescribing HIIT with RPE resulted in increased VO 2peak across high intensity intervals within single HIIT sessions and shortened TTP during high intensity intervals across CR. These findings provide evidence for a priming effect on VO 2peak during HIIT which may contribute to greater cardiopulmonary adaptations in CAD patients.