Johnson, Bruce D.

Dynamic cerebral autoregulation (CA) refers to the brain's ability to maintain stable cerebral blood flow despite fluctuations in blood pressure (BP). Impaired CA has been associated with cardiovascular disease severity and cognitive decline. On the other hand, enhanced cardiorespiratory fitness appears to be protective against both cerebrovascular dysregulation and cognitive decline, with an unclear link between the two. However, among individuals with cardiovascular disease, the impact of exercise-based cardiac rehabilitation (CR) on CA remains unclear. Therefore, the aim of this study was to test the hypothesis that a 12-week CR program would improve dynamic CA in adults with CVD. To address this question, data were collected from 14 patients enrolled in the Mayo Clinic CR program following a cardiac-related hospital admission (age: 43-70 yrs; n=3 females), which included moderate-high intensity aerobic exercise 3 times/week for 12-weeks. Continuous measures of middle cerebral artery velocity (MCAv; transcranial doppler) and finger BP (photoplethysmography) were obtained during 3-minutes of rest and a 3-minute sit-to-stand protocol (0.025Hz frequency) pre- and post the CR program. Transfer function analyses were used to provide an index of dynamic CA. BP-MCAv coherence in the low frequency (LF) and very low frequency (vLF) domains at rest were not different pre- and post- CR (LF: 0.48±0.19 vs 0.43±0.16; P=0.54; vLF: 0.51±0.12 vs 0.47±0.16; P=0.14). Similarly, gain and phase values at rest were not different pre- and post- CR (gain LF: 0.66±0.37 vs 0.58±0.33; P=0.16; vLF: 0.87±0.53 vs 0.74±0.43; P=0.21; phase LF: 0.41±0.30 vs 0.43±0.26; P=0.64; vLF: 0.72±0.53 vs 0.66±0.16; P=0.18). In contrast, during the sit-to-stand protocol, coherence was lower following CR (pre vs post LF: 0.81±0.13 vs 0.79±0.16; p<0.01; vLF: 0.80±0.09 vs 0.79±0.14; p<0.01). In addition, gain was reduced post CR (pre vs post LF: 0.59±0.35 vs 0.55±0.31; P=0.02; vLF: 0.76±0.33 vs 0.61±0.37; p<0.01), suggesting CR-induced improvements in CA efficiency. However, phase remained unchanged pre- and post- CR during the sit-to-stand protocol (LF: 1.01±0.71 vs 0.84±0.58; P=0.17; vLF: 1.16±0.69 vs 1.08±0.60; P=0.19). Taken together, these findings demonstrate that a 12-week exercise-based CR program improves dynamic CA efficiency after a cardiac event. These novel results highlight the potential role of exercise training in improving cerebrovascular regulation. Funding: NIH AG073726 and Mayo Clinic This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.

Abstract This case study investigated the impact of SCS on alterations in blood pressure during constant-load exercise in a female patient with heart failure. Three different SCS frequencies [No SCS (~0 Hz), Low SCS (~100 Hz), and High SCS (~1000 Hz)] with and without ischaemic stimulation of the legs (cuffs) were randomly applied during constant-load exercise. To determine cardiovascular and ventilatory responses to exercise following SCS frequencies, BP, heart rate (HR), and respiratory gas exchange were measured. This experiment was duplicated in visit 1 and visit 2 with a random application of SCS frequency order and the data were averaged. There were no significant differences among three frequencies with no leg ischaemia. However, High SCS demonstrated lower BP, HR, and respiratory gas exchange relative to No SCS and Low SCS. SCS may be effective in improving cardiovascular and ventilatory responses in HF and high-frequency stimulation provides more clinical benefit; however, further studies are needed.

This study investigated the combined effect of handgrip strength (HGS) and non-alcoholic fatty liver disease (NAFLD) on pulmonary function using the Korea National Health and Nutrition Examination Survey (KNHANES) from 2016 to 2018. For the present study, forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), the FEV1/FVC ratio, handgrip strength (HGS) and the hepatic steatosis index (HSI) to estimate NAFLD were obtained from nationwide cross-sectional surveys. For HGS, subjects were divided into higher HGS (upper 50%) and lower HGS (lower 50%). For NAFLD, subjects were divided into the NAFLD cohort (HSI > 36) and the normal cohort (HSI ≤ 36). Of 1651 subjects (men, n = 601), 25.5% of subjects (n = 421) met the HSI > 36. Based on the normal cohort with high HGS, the normal cohort with low HGS showed an increased risk of reduced FVC (OR = 3.062, 95% CI = 2.46–4.83, p < 0.001) and the NAFLD cohort with low HGS showed a further increased risk of reduced FVC (OR = 4.489, 95% CI = 3.43–7.09, p < 0.001). However, the risk of reduced FVC was not significantly increased in NAFLD with high HGS (OR = 1.297, 95% CI = 0.67–2.50, p = 0.436). After adjusted for covariates such as age, sex, smoking, FBG, HDL-C, TG, SBP, DBP, CRP and alcohol consumption, the results remained similar. More importantly, these results were consistent in the obesity-stratified analysis. The current findings of the study suggest that higher muscle strength is associated with a lower risk of reduced pulmonary function in individuals with NAFLD.

Fluid clearance from the alveolar space is critically dependent on epithelial sodium channels (ENaC). A common polymorphism in the gene encoding the ENaC alpha subunit results in an alanine to threonine substitution (A663T), with higher ENaC channel activity. This variant influences ion and fluid regulation in the lung during exercise and in response to albuterol. We investigated the influence of the threonine variant (T663; AT/TT group) on the lung fluid response to exercise in conditions of normobaric hypoxia, which challenges lung fluid balance. Lung fluid balance was assessed using Exhaled Na + (ENa + ) and the diffusing capacity for carbon monoxide and nitric oxide (DLCO and DLNO, respectively) to determine alveolar‐capillary membrane conductance (Dm). 19 healthy subjects were grouped by ENaC genotype (n=8 vs. 11 for AA and AT/TT, %female=50 vs. 62%, age=27±1 vs. 28±2yrs., ht=171±3 vs. 173±2cm, wt=69±6 vs.72±3kg , BMI=23±1 vs.24±1kg/m 2 ) and completed two overnight visits in a hypoxic tent simulating just over 5,400m. The visits were randomized to inhaled placebo or inhaled amiloride (1.5mg in 5ml normal saline, used to inhibit ENaC activity) with ENa + , DLCO, and Dm assessed at baseline, following 12 hours of hypoxic exposure, and following hypoxic exercise at 65% peak power on a cycle ergometer. We found significant effects of the interaction between gender and ENaC genotype on DLCO, Dm, and Dm corrected for pulmonary capillary blood volume (p<0.05). Specifically, females with the more active T663 variant had a greater diffusing capacity and less ENa + under placebo conditions, suggesting a greater removal of Na + and fluid from the airspace. These results suggest that genetic variation of ENaC may influence lung fluid balance during hypoxia and hypoxic exercise. Grant Funding Source : Supported by HL71478, HL108962‐03, and HL007249

Increased locomotor muscle afferent feedback may be linked to the reduced exercise capacity (peak VO 2 ) and poor ventilatory efficiency (high V E /VCO 2 slope) observed in heart failure (HF). We examined the relationship between peak VO 2 and change in V E /VCO 2 with afferent inhibition during exercise in HF. 9 HF (60±6 yr) and 9 controls (CTL) (63±7 yr) completed 3 visits. Visit 1: cycle exercise to volitional exhaustion. Visits 2‐ 3: 5 min constant‐load cycling (65% of peak work) randomized to lumbar intrathecal fentanyl injection (afferent block) or placebo. VO 2 , ventilation (V E ), carbon dioxide production (VCO 2 ), and end‐tidal CO 2 (P ET CO 2 ) were measured. In HF, peak work (120±34 vs 176±54 W, p <0.05) and VO 2 (18.4±2.7 vs 27.2±4.7 ml/kg/min, p <0.05) were reduced, whereas V E /VCO 2 slope was elevated (39.7±1.8 vs 35.3±0.8, p<0.05) compared with CTL. With afferent inhibition, HF patients had a greater reduction in V E /VCO 2 (‐18.8±8.1 vs ‐5.4±13.3%, p <0.05) and increase in P ET CO 2 (20.3±10.5 vs 6.1±9.5%, p <0.01) during constant‐load cycling. Lower VO 2peak was related to a greater decline in V E /VCO 2 and rise in P ET CO 2 after afferent inhibition in HF (r=0.82, p <0.01 and r=‐0.69, p <0.05, respectively) but not CTL ( p >0.05). Our data demonstrate that patients with the lowest VO 2peak have the greatest improvement in V E /VCO 2 , suggesting a close link between afferent feedback, ventilatory efficiency and exercise capacity in HF. Grant Funding Source : Supported by AHA 12GRNT11630027 and National Center for Advancing Translational Science KL2TR000136.

Cold‐water swimming is a recreational activity that may become a future Winter Olympic event. However, unintentional cold‐water exposure can lead to hypothermia or death. Changes in body temperature are known to diminish swimming performance in persons experiencing hypothermia, although thermal changes during recreational exposure are not well characterized. This study examined skin temperature responses to a one‐kilometer swim in normal and cold‐water. Competitive swimmers (2 male and 2 female; age 44±17 years; BMI 24±2) completed a one‐kilometer swim (22 laps × 75 foot lengths) under free‐living indoor (25.5°C water and 25.0°C air) and cold outdoor (10.9°C water and 6.5°C) conditions. Skin temperature was determined with a digital infrared camera on the center of right palm, cubital fossa of arm, lateral aspect of pectoral muscle, cheek, and average of the four locations at 8.7±1.7 minutes before the swim (pre), then 0.6±0.2 and 6.4±2.1 minutes after the swim. Data (mean±SD) was analyzed with repeated measures ANOVA with significance if P<0.05. Swimmers completed the indoor and outdoor swim events in 20.7±1.7 and 21.8±1.1 minutes respectively. Average indoor skin temperature at −8.7, +0.6 and +6.4 minutes was 94.0±1.7, 85.3±1.9, and 88.1±2.2°C. Average outdoor skin temperature at −8.7, +0.6 and +6.4 minutes was 83.0±3.6, 53.5±2.3, and 67.7±2.0°C. At all times average outdoor skin temperature was lower than indoor, with the lowest temperature 0.6 minutes post‐swim. Palm indoor temperature at −8.7, +0.6 and +6.4 minutes was 91.6±3.9, 83.1±0.5, and 87.3±5.0°C. Palm outdoor temperature at −8.7, +0.6 and +6.4 minutes was 75.1±7.9, 47.4±2.7, and 58.1±2.7°C. At all times outdoor palm temperature was lower than indoor, with the lowest temperature 0.6 minutes post‐swim. Similar thermal responses were observed in the cheek, cubital fossa and pectoral locations. While time to complete the indoor and outdoor one km swims were similar, swimming in cold water was associated with delayed rewarming in the palm and cheek relative to cubital fossa and pectoral muscle.