Cardiovascular autonomic dysfunction in patients with rheumatoid arthritis: contribution of peripheral chemoreflex, impact on muscle blood flow control, and exercise tolerance.

• Grant number: 22/08603-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): June 01, 2023
• Effective date (End): October 31, 2026
• Field of knowledge: Biological Sciences - Physiology - Physiology of Effort
• Principal Investigator: Hamilton Augusto Roschel da Silva
• Grantee: Indyanara Cristina Ribeiro
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Rheumatoid Arthritis (RA) presents increased cardiovascular risk, which can be caused by cardiovascular autonomic dysfunction, namely an increase in sympathetic activity and a reduction in parasympathetic activity. Impairment in cardiovascular reflex control exerted by the peripheral chemoreceptors may contribute to autonomic dysfunction in this population, however, this has not yet been investigated. Besides increasing cardiovascular risk, autonomic dysfunction in conjunction with sympathetic hyperactivity can reduce muscle blood flow during exercise, contributing to exercise intolerance and physical inactivity in RA. Hence, this project involves three studies with distinct objectives. Study 1 will investigate the effects of the peripheral chemoreflex on cardiovascular autonomic control in RA patients. Assessment of peripheral chemoreflex will be done by exposing participants to different concentrations of gases (i.g., normoxia, hypoxia and hyperoxia). For this, 16 RA women and 16 age-, body mass index (BMI)- and cardiovascular risk-matched controls will be recruited. Heart rate (HR), blood pressure (BP), muscle blood flow and ventilation (VE) will be recorded during chemoreflex evaluation. These parameters will be compared between sessions and groups using mixed model analysis (p<0.05). Study 2 will investigate if patients with RA have impaired blood flow regulation to active muscles during exercise, possibly caused by sympathetic hyperactivity. For this purpose, 17 RA patients and 17 age-, BMI - and cardiovascular risk-matched controls will be recruited. Participants will perform two experimental sessions, which will consist of handgrip exercise followed by cycle ergometer for lower limbs. In one of the sessions, sympathetic activity will be partially inhibited by administration of an alpha-adrenergic receptors blocker (i.e., phentolamine). During both sessions, peripheral muscle blood flow will be assessed at rest and during exercise by a Doppler ultrasound, positioned in the brachial artery for handgrip exercise, and in superficial femoral artery for cycle ergometer. Exercise tolerance will be assessed by the cardiovascular, ventilatory and perceptual responses to the exercises. These parameters will be compared between sessions and groups using mixed model analysis (p<0.05). Study 3 will investigate the association between levels of physical activity/sedentary behavior and blood flow regulation to active muscles during exercise in RA patients. This study will include 40 individuals with RA. Participants will perform an experimental session, which will consist of handgrip exercise followed by cycle ergometer for lower limbs. During the session, peripheral muscle blood flow will be assessed at rest and during exercise by a Doppler ultrasound, positioned in the brachial artery for handgrip exercise, and in superficial femoral artery for cycle ergometer. Moreover, cardiovascular, ventilatory and perceptual responses to the exercises, will be assessed during the entire protocol. The associations will be tested using simple and multiple regression analysis (p<0.05). The results of this study may advance the understanding of the mechanisms underlying the increased cardiovascular risk and exercise intolerance in RA, which could be used to support pharmacological or non-pharmacological interventions targeting the cardiovascular management in this population.