Peripheral Chemoreceptors Hemodynamic Responses During Simulated Hemorrhage Under Hypoxia Conditions

Abstract

BackgroundMaintaining baroreflex sensitivity is integral to ensuring blood pressure maintenance and end‐organ perfusion during hemorrhage. This is especially true under conditions of hypoxemia, where decreased tolerance to central hypovolemia is commonly observed. Hypoxia activates peripheral chemoreceptors and reduces baroreceptor‐vascular resistance reflex sensitivity. However, a direct role for the peripheral chemoreceptors in the hemodynamic response to hemorrhage in hypoxia remains unclear.ObjectiveWe tested the hypothesis that attenuation of peripheral chemoreceptor activity (low‐dose dopamine; 1–2 μg/kg/min) during acute hypoxia would promote maintenance of mean arterial pressure, pulse pressure, and other hemodynamic markers [heart rate (HR), stroke volume (SV), cardiac output (CO), total peripheral resistance (TPR)] during simulated hemorrhage.MethodsTen healthy men (35±3 years, BMI 25±1 kg/m2) participated in a randomized, double‐blind, placebo controlled study. Participants completed two experimental visits (saline and low‐dose dopamine) at which lower body negative pressure (LBNP) was conducted during hypoxia (SpO2 ~85%; PaO2 ~52 mmHg) delivered via a non‐rebreather mask. Ventilation [V̇ (turbine transducer)], arterial blood pressure (brachial artery catheter), HR (ECG), and central venous pressure (peripherally inserted central catheter) were measured continuously and SV, CO, and TPR were calculated. Following a 5‐min rest, participants underwent LBNP for 5‐min at 3 intervals (−15, −30, and −45 mmHg). Outcome values were analyzed and compared using a mixed linear model (SAS PROC MIXED) with a direct product AR(1) covariance structure using indicator variables for saline vs. dopamine. Data from the mixed linear model are reported as an estimated change per 15 mmHg of LBNP.ResultsDopamine had no effect on hypoxia PaO2, PaCO2, V̇ or respiratory rate (all P>0.05) and this relationship persisted throughout all LBNP stages. The mixed linear model showed no effect of dopamine vs. saline on changes in: central venous pressure (−1.1±0.4 vs −1.3±0.3 mmHg, P=0.15), mean arterial pressure (−4.7±2.3 vs −5.3±1.4 mmHg, P=0.25), pulse pressure (−6.7±1.5 vs −8.3±1.4 mmHg, P=0.50), HR (7.8±1.5 vs 6.1±1.5 bpm, P=0.41), SV (−10.9±1.9 vs −11.6±3.3 mL, P=0.41), CO (−0.3±0.2 vs −0.4±0.4 L · min−1, P=0.31) or TPR (0.2±0.4 vs 0.7±0.6 mmHg · L · min−1P=0.27).DiscussionIntravenous infusion of low‐dose dopamine designed to attenuate peripheral chemoreflex activity during acute hypoxia did not alter the integrated hemodynamic response to simulated hemorrhage. Our data suggests that peripheral chemoreceptors have a limited role during hypoxic central hypovolemia. More research is needed to understand the sensitivity and cross‐talk between chemoreceptors and baroreceptors during hemorrhage.Support or Funding InformationFunding: W81XWH‐13‐2‐0038 (DOD), DK90541 (NIH), UL1 TR000135 (NIH).