THE EFFECT OF NORMOBARIC HYPOXIA AND METABOREFLEX IN THE CARDIOVASCULAR ADJUSTMENTS TO EXERCISE

INTRODUCTION It is well established that both hypoxia and metaboreflex have a great impact on the cardiovascular system, exerting both contrasting and complementary effects on heart rate (HR), cardiac output (CO), ventilation (VE), stroke volume (SV) and systemic vascular resistance (SVR). However, evidence on the interaction between hypoxia and metaboreflex when concomitantly active is still lacking. The aim of my study was to better elucidate this topic, focusing on hemodynamic parameters that have never been studied in the past in this context (like SV, BP, and SVR). To reach this goal, I performed 2 series of experiments in which were evaluated the effects of a previous dynamic exercise bout in hypoxia (Experiment 1) and the simultaneous exposure to hypoxia (Experiment 2) on metaboreflex activation. MATERIALS AND METHODS Experiment 1 was conducted recruiting 17 well-trained subjects (7 females, 10 males) that underwent a cardiopulmonary exercise test (CPET) to asses their fitness. Then, the athletes performed a 10-minute rectangular exercise bout on a cycle ergometer in normoxia and in normobaric hypoxia at two different levels of fraction of inspired oxygen (15,5% and 13,5 % of FiO2 ) in three separate days after randomization. Each exercise session was followed by a metaboreflex-activating protocol in normoxia that consisted of 2 sessions called post-exercise muscle ischemia (PEMI) and control exercise recovery (CER). PEMI and CER both included 3 minutes of rest and 3 minutes of exercise at 30% of the maximum wattage (Wmax) reached during the CPET. After the exercise, PEMI was followed by a 3-minute application of an inflatable thigh cuff to induce a temporary occlusion of the arterial and venous vascular bed and 3 minutes of rest. Regarding CER, the exercise was followed by 6 minutes of resting without occlusion and was used as control. In experiment 2, 11 moderately-fit male subjects were recruited. After CPET, the subjects underwent a PEMI/CER session in normoxia and hypoxia (13,5 % of FiO2 ) in 2 separate days. The variables analyzed in experiment 1 and 2 were SV, CO, HR, ventricular filling rate (VFR, a measure of cardiac diastolic function/preload) and ventricular ejection rate (VER a measure of cardiac inotropism) by means of impedance cardiography, mean BP by manual sphygmomanometer and SVR indirectly from CO and BP according to Poiseuille's law. Moreover, I measured cerebral tissue oxygenation (COX) and peripheral hemoglobin saturation (SPO2) by means of near-infrared spectroscopy (NIRS) throughout all the experimental sessions to check if the hypoxia was effective.    RESULTS In both experiments 1 and 2, I evidenced a significant reduction of SV, CO and VFR response during metaboreflex activation when the hypoxic stimulus was applied while SVR response was increased preventing BP from dropping as a consequence of SV reduction. DISCUSSION My results demonstrate that hypoxia can impair SV response to metaboreflex activation. This mechanism is likely related to a reduced left ventricular (LV) preload as VFR decreased when the hypoxic stimulus was applied. Two possible explanations could be proposed to explain my results. Firstly, hypoxia could have stimulated nitric oxide (NO) production in the venous vascular bed with a consequent venodilation and reduced venous return to the heart, impairing the recruitment of the Frank-Starling mechanism to increase SV. Secondly, hypoxia has a vasoconstrictor effect on the pulmonary arterial bed that could have increased right ventricular (RV) afterload, reducing the amount of blood returning to the LV from the pulmonary vascular bed and impairing LV preload. Moreover, SVR response increased both in experiments 1 and 2, counterbalancing the potential BP drop that could have taken place as a consequence of SV reduction. Thus, it can be speculated that metaboreflex activation overcame the vasodilatory effect of hypoxia-mediated NO production on peripheral arteries.​