Cardiovascular Effects of the Exercise Pressor Reflex and Carotid Chemoreflex Interaction in Patients with Heart Failure with Reduced Ejection Fraction
Authors: Wan Hsuan-Yu , Weavil Joshua , Georgescu Vincent , Thurston Taylor , Laginestra Fabio , Broxterman Ryan , Birgenheier Nathaniel , Morgan David , Tuday Eric , Stehlik Josef , Amann Markus 
Published: May 2023

Background: The interaction of the exercise pressor reflex (EPR) and the carotid chemoreflex (CR) affects circulatory control during physical activity in health. It has been shown that patients with heart failure with reduced ejection fraction (HFrEF) have an abnormal cardiovascular response to EPR or CR activation, which contributes to impaired limb blood flow during exercise. However, the impact of the reflex interaction in HFrEF is unclear. Purpose: To evaluate the interaction between EPR and CR in HFrEF. Method: Five patients with HFrEF and 6 control subjects (Ctrl) completed two experimental sessions. In session 1, participants performed dynamic single-leg knee-extension at 60% of peak power output for 4 min while breathing room air (normoxia; NormC: SaO2~96%, PaO2~81 mmHg, PaCO2~33 mmHg, arterial pH~7.43) and pure O2 (hyperoxia; HyperC: SaO2~100%, PaO2~408 mmHg, PaCO2~35 mmHg, arterial pH~7.40). In session 2, following lumbar intrathecal fentanyl administration to attenuate group III/IV leg muscle afferent feedback, participants repeated the same exercise under normoxic and hyperoxic conditions (NormF and HyperF). Mean arterial pressure (MAP, radial artery catheter), heart rate (HR, 12-lead ECG), stroke volume (SV, finger photoplethysmography), cardiac output (CO), systemic vascular conductance (SVC), femoral blood flow of the working leg (LBF, Doppler ultrasound), and leg vascular conductance (LVC) were continuously quantified during exercise. Results: EPR activation (i.e., ΔHyperC-HyperF) in HFrEF resulted in no changes in MAP and HR, but significantly decreased SV (~10 mL), CO (~1 L min−1), SVC (~9 mL min−1 mmHg−1), LBF (~0.4 L min−1) and LVC (~4 mL min−1 mmHg−1). In contrast, EPR activation in Ctrl significantly increased MAP (~10 mmHg) and decreased LVC (~3 mL min−1 mmHg−1), but did not affect HR, SV, CO, SVC and LBF ( p≥0.20). CR activation in HFrEF (i.e., ΔNormF-HyperF) had no effects on any of the cardiovascular variables ( p≥0.12). CR activation in Ctrl significantly increased HR (~3 beats min−1) and SVC (~3 mL min−1 mmHg−1), but had no effects on MAP, SV, CO, LBF and LVC ( p≥0.10). During EPR:CR co-activation (i.e., ΔNormC-HyperF) in HFrEF, the observed responses were not significantly different from the sum of the responses evoked by each reflex individually. In Ctrl, MAP during EPR:CR co-activation was greater than the summated response (16±7 vs. 10±9 mmHg; p<0.01) and SV and SVC were significantly lower than the summated responses; there were no differences between the observed and summated responses of other parameters. Conclusion: Our findings indicate that during exercise in healthy older adults, EPR and CR interact to synergistically augment MAP by constricting vessels in non-active tissue/organs, which may facilitate blood flow to the exercising limb. The circulatory consequences of the reflex interaction appear to be altered in HFrEF and contribute to the impaired limb blood flow characterizing this population during exercise. National Heart, Lung, and Blood Institute (HL-116579), U.S. Veterans Affairs Rehabilitation Research and Development (E3343-R) 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.