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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

Grant number: 15/22198-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2016
Effective date (End): October 21, 2018
Field of knowledge:Biological Sciences - Physiology - General Physiology
Principal researcher:Bruno Moreira Silva
Grantee:Marcelle de Paula Ribeiro
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil


Pulmonary Arterial Hypertension (PAH) is a chronic disease with varied etiology and unfavorable prognosis. The disease is accompanied by autonomic dysfunction, which is characterized by decreased parasympathetic activity and increased sympathetic activity to the cardiovascular system. One of the mechanisms that may contribute to the autonomic dysfunction in PAH is the increase in peripheral chemoreflex activity since its inhibition reduced the sympathetic nervous activity in this population. However, it is still unclear the tonic contribution of this reflex to the vagal control of the heart, which then will be the focus of investigation of the present project. Our hypothesis is that the peripheral chemoreflex impairs the vagal control of the heart at rest and in ortostatism in PAH and can be even clearer at rest during the recovery from physical exercise, since this reflex has been shown to be potentiated by metabolic acidosis, among other mechanisms related to exercise. To test this hypothesis, we will recruit patients with PAH and healthy subjects paired for gender and age. All of them will be randomly exposed to hyperoxia (inhibition of the peripheral chemoreflex tonus via inhalation of 100% O2) or normoxia (control experiment via inhalation of 21% O2) during the evaluation of the vagal control of the heart by methods that are pharmacologically validated, reproducible and have strong prognostic power for cardiac arrhythmias and death in cardiorespiratory disease. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
PAULA-RIBEIRO, MARCELLE; RIBEIRO, INDYANARA C.; ARANDA, LILIANE C.; SILVA, TALITA M.; COSTA, CAMILA M.; RAMOS, ROBERTA P.; OTA-ARAKAKI, JAQUELINA S.; CRAVO, SERGIO L.; NERY, LUIZ E.; STICKLAND, MICHAEL K.; SILVA, BRUNO M. Carotid chemoreflex activity restrains post-exercise cardiac autonomic control in healthy humans and in patients with pulmonary arterial hypertension. JOURNAL OF PHYSIOLOGY-LONDON, v. 597, n. 5, p. 1347-1360, MAR 1 2019. Web of Science Citations: 0.
SABINO-CARVALHO, JEANN L.; OBEID-FREITAS, TIAGO; PAULA-RIBEIRO, MARCELLE; LOPES, THIAGO R.; FERREIRA, THIAGO H. N.; SUCCI, JOSE E.; SILVA, ANTONIO C.; SILVA, BRUNO MOREIRA. Ischemic preconditioning boosts post-exercise but not resting cardiac vagal control in endurance runners. EUROPEAN JOURNAL OF APPLIED PHYSIOLOGY, v. 119, n. 3, p. 621-632, MAR 2019. Web of Science Citations: 1.
SILVA, TALITA M.; ARANDA, LILIANE C.; PAULA-RIBEIRO, MARCELLE; OLIVEIRA, DIOGO M.; MEDEIROS, WLADIMIR M.; VIANNA, LAURO C.; NERY, LUIZ E.; SILVA, BRUNO M. Hyperadditive ventilatory response arising from interaction between the carotid chemoreflex and the muscle mechanoreflex in healthy humans. Journal of Applied Physiology, v. 125, n. 1, p. 215-225, JUL 2018. Web of Science Citations: 6.

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