Neurovascular and cardiorespiratory coupling in Rheumatoid Arthritis patients: underlying mechanisms and a proposal of non-pharmacological countermeasure

• Grant number: 22/15852-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: August 01, 2023
• End date: October 31, 2023
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Bruno Gualano
• Grantee: Gabriel Dias Rodrigues
• Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

The baroreflex control plays a role to main adequate cerebral perfusion pressure gradient, buffering large oscillations in blood pressure. The brain, in this turn, has intrinsic mechanisms of cerebral blood flow regulation (cerebral autoregulation) and coupling with brain activity (neurovascular coupling). Patients with Rheumatoid Arthritis (RA) may have reduced baroreflex sensitivity (BRs) and endothelial function. Recently, diminished cognitive function has been observed in patients with RA, but without a clear statement of the underlying mechanisms. Both BRs and neurovascular coupling are reduced in mild cognitive impairment (MCI) and Alzheimer's disease; however, it is unclear if this mechanism is involved in the reduced cognition function of RA patients. In turn, inspiratory muscle training (IMT) is a non-pharmacological strategy that can amplify the cardiorespiratory coupling, reduce inflammation, and improve cardiovascular autonomic control and endothelial function in older adults. However, it is unknown if a similar effect could be found in RA patients. To test these hypotheses, the project was divided into two steps: (1) an exploratory and mechanistic study will investigate whether neurovascular coupling and BRs are associated with reduced cognitive function in RA; (2) a randomized clinical trial will investigate whether IMT can attenuate cardiovascular autonomic and endothelial dysfunctions, and reduce inflammation in RA. Furthermore, IMT could increase BRs and improves the neurovascular coupling and cognition in these patients. For this purpose, 50 women with RA and 50 healthy women, composing the control group, will enroll in stage I: (a) a cardiovascular autonomic assessment; (b) a neurovascular coupling and cognitive function assessments; (c) measurement of pro-inflammatory cytokines; (d) endothelial function assessment; and (e) global clinical assessment. In step II, 50 women with RA will be randomized into two groups: the experimental group will perform the IMT through an inspiratory resistor set at 60% of the maximum inspiratory pressure (MIP), 30 breaths, twice a day for 6 weeks. The placebo group (PLA) will perform the same schedule, except for the inspiratory load, which will be set at 10% of the MIP. Both interventions will be based at home and monitored once a week through a video call with the participants. The step I assessments will be performed before and after the interventions (TMI and PLA). The project results may contribute to a better understanding of the pathophysiology of cognitive dysfunction in RA and the application of IMT as a potential strategy to counterbalance the deteriorative effects of RA disease. (AU)