A Pilot Study to Investigate the Effect of Hypercapnia Training on Cerebrovascular Reactivity in Healthy Adults
Authors: Taylor Jenna L. , Lavey Jack A. , Carlson Alex R. , Barnes Jill N. , Johnson Bruce D. 
Published: May 2022

ObjectiveHypercapnia, 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.HypothesisRepeated bouts of hypercapnia (as interval training) may promote beneficial adaptation to increase cerebrovascular reactivity.MethodsAdults 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.ResultsSix 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].ConclusionPreliminary 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.