THE CONTRIBUTION OF PERIPHERAL CHEMOREFLEX TO HYPOXIC PULMONARY HYPERTENSION IN HEALTHY HUMANS

• Grant number: 17/04019-9
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Effective date (Start): July 29, 2017
• Effective date (End): December 19, 2017
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Bruno Moreira Silva
• Grantee: Marcelle de Paula Ribeiro
• Supervisor: Bryan Joseph Taylor
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Research place: University of Leeds, England
• Associated to the scholarship: 15/22198-2 - Tonic contribution of the peripheral chemoreflex to vagal control of the heart at rest, Orthostatism and recovery from exercise in patients with pulmonary arterial hypertension, BP.DR

Abstract

Pulmonary Arterial Hypertension (PAH) is a rare and progressive disease that affects the pulmonary vasculature. It is characterized by increase in resting pulmonary arterial pressure (PAP) and pulmonary vascular resistance (PVR) leading to right heart failure and death. Despite the pathophysiology of most forms of PAH remaining unclear, it is well established that autonomic nervous system dysfunction is a hallmark and may be related to the disease severity. Evidences have shown the contribution of peripheral chemoreflex to the sympathetic hyperactivity in this population. Data of my current PhD project indicates that the peripheral chemoreflex also contributes to the cardiac vagal modulation in PAH, suggesting that this reflex might have an important role in autonomic nervous system dysfunction in PAH. Regardless of pulmonary hypertension (PH) etiology, the impaired pulmonary vascular function and consequently pulmonary vasoconstriction is a hallmark and a neural mechanism may play a role. Based on the evidences indicating the role of the peripheral chemoreflex on modulation of autonomic nervous system in patients with PH, it is possible that when stimulated, the peripheral chemoreflex could also contribute to the modulation of the pulmonary vasculature in this population. thus, the aim of the current project is to assess the contribution of peripheral chemoreflex to hypoxic PH model in healthy humans . For this purpose,10 young healthy men will perform a protocol of hypoxic PH (FiO2 = 12%) under 2 situations (random order): the inhibition of peripheral chemoreflex through the infusion of different doses of dopamine or a control condition through saline infusion . During rest, hypoxia inhalation and infusions of dopamine and saline, the systolic PAP, PVR and other pulmonary and cardiac function variables will be estimate using the doppler-echocardiography measurements. Data will be expressed as mean ± standard deviation. The systolic PAP, PVR and other variables will be compared between conditions using paired Student's t test or one-way repeated measure ANOVA (P < 0.05).