INTEGRATED EFFECTS OF NORMOBARIC HYPOXIA AND METABOREFLEX ACTIVATION ON HEMODYNAMICS

Abstract

IntroductionBoth metaboreflex activity and hypoxia affect hemodynamics. In particular, metaboreflex induces an augmentation in stroke volume (SV), systemic vascular resistance (SVR), and blood pressure (BP) by activating the sympathetic nervous system (SNS). In contrast, hypoxia produces a heart rate (HR)‐mediated increase in cardiac output (CO), while its effect on SVR is variable as it increases SNS activity but, at the same time, it triggers nitric oxide (NO) production in the endothelium, thus inducing venous and arteriolar dilation. Since studies on the possible interaction between metaboreflex and hypoxia are still lacking, our investigation aimed to study their combined effects on hemodynamics.Methods11 male subjects underwent a preliminary cardiopulmonary exercise test (CPET) on a cycle ergometer to assess their aerobic fitness. Then, a metaboreflex activation protocol in normoxia and normobaric hypoxia (fraction of inspired oxygen – FiO2 – of 13.5%) was conducted on separate days. Hypoxia was induced using a hypoxic gas generator (Everest Summit II Generator, Hypoxico, USA) connected to the subjects by a facemask. The metaboreflex activation protocol consisted of two randomly assigned sessions: one of post‐exercise muscle ischemia (PEMI) and one of control exercise recovery (CER). PEMI comprised a 3‐minute exercise bout pedaling at 30% of the maximum workload reached during the CPET followed by 3 minutes of vascular occlusion using an inflatable thigh cuff to stimulate the metaboreflex. CER was similar, but no occlusion was applied after the exercise session. SV, HR, CO, ventricular filling rate (VFR), and ventricular ejection rate (VER) were measured through impedance cardiography while mean blood pressure (MBP) was assessed using manual sphygmomanometer. SVR was calculated indirectly from CO and MBP according to Poiseuille’s law. Near‐infrared spectroscopy was employed to measure cerebral oxygenation (COX) and peripheral hemoglobin saturation (SPO2) to control the level of tissue hypoxia. Two‐way ANOVA and paired sample t‐test were utilized when appropriate.ResultsCO was increased during metaboreflex activation in normoxia (p= 0.013) but not in hypoxia. SV, CO, and VFR responses to metaboreflex (measured as the difference PEMI‐CER at the third minute after exercise) were reduced when the hypoxic stimulus was applied (p=0.02; p=0.02; p=0.003 respectively). Moreover, SVR response showed a nearly significant (p=0.07) increase in hypoxia, with MBP response being unchanged. COX and SPO2 confirmed that the hypoxic stimulus was effective.DiscussionResults demonstrated that hypoxia impaired the hemodynamic response to metaboreflex. Specifically, SV was reduced during metaboreflex in hypoxia because of a reduction in preload as a consequence of two mechanisms: 1) a reduction in venous return probably induced by NO‐mediated vasodilation of the venous bed; 2) an increase in right ventricle afterload likely produced by the pulmonary arterial system vasoconstriction. Of note, baroreflex successfully defended MBP response despite the reduced CO during hypoxia.