Carlson, Alex R.

Objective Hypercapnia, an elevated concentration of carbon dioxide (CO2) in the blood, is known to promote acute increases in cerebral blood flow (CBF). This pilot study aimed to investigate whether a novel training method involving repeated bouts of hypercapnia, would influence cerebrovascular reactivity response in healthy adults. Hypothesis Repeated bouts of hypercapnia (as interval training) may promote beneficial adaptation to increase cerebrovascular reactivity. Methods Adults over 40yrs old without known disease or cardiovascular risk factors, were recruited for a non‐randomized cross‐over design pilot study. Subjects completed a 2‐week control period followed by a 2‐week intervention. The intervention involved a progressive hypercapnia training program of six sessions, whereby subjects completed 4‐6 intervals of rebreathing oxygen until a target end‐tidal CO2 (up to 25mmHg above resting) was reached, separated by recovery intervals breathing room air. Cerebrovascular reactivity was measured during study testing visits at baseline, 2‐weeks (between control and intervention) and 4‐weeks (after intervention). During study visits subjects underwent a stepped CO2 protocol, involving 5‐min stages of inspired room air, 2% CO2, 4% CO2, and 6% CO2, while measuring middle cerebral artery velocity (CBFv) using transcranial doppler ultrasound, mean arterial pressure (MAP) by finger plethysmography, ventilation, and end‐tidal CO2. Cerebrovascular conductance (CVCi) was calculated as CBFv/MAP. The reactivity of CBFv (in cm/s/mmHg), CVCi (in cm/s/mmHg2), and MAP (in mmHg/mmHg) were calculated as the linear regression slope against end‐tidal CO2 during the stepped CO2 protocol. Chemosensitivity (in L/min/mmHg) is the linear regression slope of VE vs end‐tidal CO2. Results Six healthy adults (age: 56 ± 10; 2 females) completed the study. Study visit data are displayed in Table 1. Individual training data are presented in Table 2. Following the control period there was a large reduction from baseline in CBFv reactivity [2.81 ± 1.50 to 2.03 ± 1.03; effect size 0.9], CVCi reactivity [0.020 ± 0.015 to 0.015 ± 0.010; effect size 0.7], and MAP reactivity [0.95 ± 0.63 to 0.62 ± 0.42; effect size 0.6] with no change in chemosensitivity [0.99 ± 0.68 to 0.98 ± 0.51; effect size 0.0]. Following the intervention there was no change from the 2‐week study visit in CBFv reactivity [2.03 ± 1.03 to 2.01 ± 1.09; effect size 0.0], CVCi reactivity [0.015 ± 0.010 to 0.014 ± 0.010; effect size 0.1], and MAP reactivity [0.62 ± 0.42 to 0.72 ± 0.44; effect size 0.1] with a small increase in chemosensitivity [0.98 ± 0.51 to 1.04 ± 0.53; effect size 0.3]. Conclusion Preliminary findings suggest a very brief progressive hypercapnia training program does not increase or desensitize cerebrovascular reactivity in healthy adults. These data also suggest an exaggerated cerebrovascular reactivity response may occur to an initial exposure of a stepped CO2 protocol (without familiarization), which appears to be driven by blood pressure response not chemosensitivity. Further research, particularly in populations with impaired cerebrovascular reactivity, is of interest for CBF regulation.

BACKGROUND Increased activation of Group III/IV skeletal muscle afferents is suggested to play a role in exercise intolerance in heart failure (HF). PURPOSE The purpose of this study was to examine if skeletal muscle afferent feedback inhibition improves exercise tolerance in HF. METHODS 8 HF patients [59±8 yr, mean±SD] participated in two randomized incremental recumbent cycling exercise sessions to peak capacity (peak oxygen consumption, VO 2 ). Session 1: The synthetic opioid fentanyl (50 mcg), known to block afferent feedback, was injected intrathecally (INJ) in the lumbar spine (L3‐L4 intervertebral space) prior to exercise. Session 2: Participants were prepared similarly with a sham injection (placebo, PLA). Gas exchange, dyspnea and RPE were measured. RESULTS HF patients exercised for a longer duration (Δ3±3 min, p=0.02) and reached a higher power output (PLA:109±30 vs. INJ:128±34 W, p=0.02) with locomotor afferent inhibition. Additionally, peak VO 2 was non‐significantly greater (PLA:18.7±3.3 vs. INJ:21.8±4.4 ml/kg/min, p=0.10). With INJ workload matched to peak PLA workload, RPE was reduced (PLA:18±2 vs. INJ:15±2, respectively, p=0.005) and dyspnea was lower (PLA:7.5±2 vs. INJ:4.2±1, p=0.003) with no difference in VO 2 (p>0.05). CONCLUSION Inhibition of group III/IV locomotor muscle afferent feedback contributes to improved exercise tolerance and exertional symptoms in HF patients.

BACKGROUND High altitude (HA) exposure influences appetite, protein synthesis and breakdown, and aerobic capacity. Thus, HA exposure typically causes weight (wt) loss, while the impact on aerobic capacity upon return to sea level is more variable. OBJECTIVE To examine the influence of hypobaric hypoxia on body composition and exercise capacity in elite HA climbers (n=4, 2 female) acclimating at ≥5,150 m over 2 mo. relative to trekkers (n=8, 0 female) acclimating at 5,150 m over 2 wks (Mt. Everest, Nepal). Each elite climber successfully summited Mt. Everest. METHODS Body composition (DEXA, skin folds, wt) and exercise capacity (treadmill) were assessed before and within 2 wks post HA. RESULTS HA exposure increased Hct and Hb, with peak values of 52±5% and 18±2 g/dl, and 50±3% and 17±1 g/dl for the climbers and trekkers, respectively. HA decreased lean and fat tissue in both the climbers (lean −4.4±2.3%, fat −8.2±4.0%) and trekkers (lean −1.8±1.6%, fat −5.8±6.1%) (all P ≤0.06). No change was observed in skin folds for either group. Wt decreased in the climbers (−5±2%, P <0.03) and trekkers (−3±1%, P <0.01). There was no change in VO 2max pre‐to post‐HA in either group (climbers 3.26 ± 0.37 vs. 3.27 ± 0.61 L/min; trekkers 3.60 ± 0.54 vs. 3.66 ± 0.43 L/min). CONCLUSION HA results in both lean and fat tissue loss in well acclimatized climbers and trekkers with little subsequent impact on aerobic capacity. Mayo Clinic & TNF.

Background Fluid flux in the lungs is influenced by factors altering accumulation or removal (e.g., stimulation of epithelium sodium channels, ENaC). Purpose To determine if ENaC are necessary in the normal fluid regulation with simulated altitude exposure. Methods/Results On separate occasions, 19 healthy subjects (27 ± 5 y) received either nebulized amiloride (ENaC antagonist) or placebo (nebulized saline) during 17 h normobaric hypoxia (FIO2 = 12.5%) in a randomized, double‐blind fashion. Lung diffusing capacity for carbon monoxide (DLCO), alveolar‐capillary membrane conductance (Dm) and pulmonary capillary blood volume (Vc) were measured via a rebreathe method before and after hypoxic exposure. DLCO was not different at baseline for the amiloride vs. placebo treatments (19 ± 5 vs. 21 ± 8 mL/min/mmHg). Hypoxic exposure increased Vc but did not change Dm in both treatments (Placebo: Vc = 43 ± 22 vs. 59±23 mL p=0.011, Dm = 35 ± 10 vs. 37 ± 12 mL/min/mmHg p=0.312; Amiloride: Vc = 38 ± 17 vs. 57 ± 22 mL p<0.01, Dm = 31 ± 8 vs. 34 ± 10 mL/min/mmHg p= 0.206). Conclusion Normobaric hypoxia did not differentially affect alveolar‐capillary conductance in amiloride and placebo conditions, suggesting that ENaC do not have a role in normal lung fluid regulation during acute hypoxic exposure. HL71478