Contribution of central hemodynamics and end-tidal CO2 to cerebrovascular dynamics during aerobic exercise

During aerobic exercise, central hemodynamics and CO2 partial pressure are central to middle cerebral artery blood velocity (MCAv) response. Still, the extent of their contribution is unknown. The purpose of this study was to characterize and utilize statistical modeling to determine the contribution of heart rate (HR), mean arterial pressure (MAP), and end-tidal CO2 (PETCO2) dynamics to MCAv dynamics. Three randomized exercise bouts were completed on a recumbent stepper at 30-40% (Low), 45-55% (Mod1), and 60-70% (Mod2) of estimated HRmax. A 90-s resting period was followed by 6-min of continuous exercise within the estimated HR ranges. HR, MAP, PETCO2, and MCAv exercise dynamics were modeled with a monoexponential curve. From this modeling, the baseline (BL), time delay (TD), time constant (τ), and steady-state (SS) responses were determined. Backward AIC linear regression models determined contributing dynamics. Seventeen healthy adults completed all exercise bouts (28 ± 6 yrs, 8 females). The time from initiation of exercise to an exponential increase in HR (HRTD) was significantly longer for Low than Mod2 (p=0.047). The time constant for the rise in HR (HRτ) was significantly shorter for Low than Mod1 and Mod2 (p=0.01). The absolute change in HR from baseline to steady-state (HRSS) was significantly lower for Low than Mod1 and Mod2 (p<0.001), and Mod1 was significantly lower than Mod2 (p<0.001). MAPSS was significantly lower for Low than Mod1 (p=0.01) and Mod2 (p<0.001). Exercise intensity, HRTD, and MAPTD accounted for 17% of variation for MCAvTD (p=0.01). HRTD, PETCO2TD, and MCAvTD accounted for 21% of variation MCAvτ (p<0.01). MCAvτ, MAPSS, and PETCO2SS accounted for 60% of variation for MCAvSS (p<0.001). Throughout the MCAv dynamic response pathway central hemodynamics and end-tidal CO2 do not account for most MCAv response until the steady-state phase. Thus, other physiological factors should be considered with assessing cerebrovascular function during aerobic exercise. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement The authors disclosed receipt of the following financial support for the research, authorship, and publication of this article. SA was supported by a Clinical and Translational Science Award (CTSA) from the National Center for Advancing Translational Sciences (NCATS), which was awarded to the University of Kansas for Frontiers: the University of Kansas Clinical and Translational Science Institute (# TL1TR002368). AW was supported by the American Heart Association Predoctoral Fellowship Grant (898190), the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health (T32HD057850) and the National Heart, Lung, and Blood Institute (T32HL134643). Additional support was provided by the National Institute on Aging P30 AG072973 grant. The contents are solely the authors' responsibility and do not necessarily represent the official views of the NCATS or the National Institutes of Health. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The protocol was reviewed and approved by the University of Kansas Medical Center's institutional review board (IRB number STUDY00003176). Research was conducted in accordance with the principles embodied in the Declaration of Helsinki and in accordance with local statutory requirements. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data underlying the results presented in the study are available upon reasonable request from the corresponding author.