Tonic contribution of the peripheral chemoreflex to the vagal control of the heart at rest and recovery from exercise in patients with chronic heart failure

• Grant number: 14/24294-6
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2015
• End date: June 30, 2017
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Bruno Moreira Silva
• Grantee: Bruno Moreira Silva
• Host Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
• Associated researchers: Antônio Carlos da Silva ; Flávio Ferlin Arbex ; Luiz Eduardo Nery ; Marcelle de Paula Ribeiro ; Maria Clara Noman de Alencar ; Roberta Pulcheri Ramos ; Sergio Luiz Domingues Cravo

Abstract

Chronic Heart Failure (CHF) is a disease that has high prevalence 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 contribute to the autonomic dysfunction in CHF is the increase in peripheral chemoreflex sensitivity to hypoxia. However, it is still unclear what is the tonic contribution of this reflex in normoxia, mainly with regards 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 in CHF, not only when this reflex is stimulated by hypoxia, but also tonically in normoxia. Such impairment can be even clearer during the recovery from physical exercise, since this reflex has been shown to be potentiated by metabolic acidosis, among other mechanisms related to exercise. Therefore, the peripheral chemoreflex can exhibit a larger contribution to the autonomic dysfunction in CHF at rest and during the recovery from exercise than is known so far. To test this hypothesis, we will recruit patients with CHF and enhanced chemosensitivity, as well as patients with CHF and normal chemosensitivity. All of them will be randomly exposed to hyperoxia (inhibition of the peripheral chemoreflex tonus) or normoxia (control) 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 CHF. If our hypothesis is confirmed, the results will highlight the need for innovative strategies to treat patients with CHF, aiming to reduce the chemoreflex tone, and thus improve the poor prognosis of this population. (AU)

Scientific publications

(6)

(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)

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. (15/22198-2, 16/01155-6, 14/24294-6)

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.; et al. 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. (15/22198-2, 16/23622-5, 14/24294-6, 16/01155-6)

SABINO-CARVALHO, JEANN L.; LOPES, THIAGO R.; OBEID-FREITAS, TIAGO; FERREIRA, THIAGO N.; SUCCI, JOSE E.; SILVA, ANTONIO C.; SILVA, BRUNO M.. Effect of Ischemic Preconditioning on Endurance Performance Does Not Surpass Placebo. MEDICINE AND SCIENCE IN SPORTS AND EXERCISE, v. 49, n. 1, p. 124-132, JAN 2017. (14/15877-8, 15/03572-0, 14/24294-6)

SAYEGH, ANA LUIZA C.; SILVA, BRUNO MOREIRA; FERREIRA, ELOARA V. M.; RAMOS, ROBERTA P.; FISHER, JAMES P.; NERY, LUIZ E.; OTA-ARAKAKI, JAQUELINA S.; OLIVEIRA, RUDOLF K. F.. Clinical utility of ventilatory and gas exchange evaluation during low-intensity exercise for risk stratification and prognostication in pulmonary arterial hypertension. Respirology, v. 26, n. 3, OCT 2020. (14/24294-6)

PAULA-RIBEIRO, MARCELLE; RIBEIRO, INDYANARA C.; ARANDA, LILIANE C.; SILVA, TALITA M.; COSTA, CAMILA M.; RAMOS, ROBERTA P.; OTA-ARAKAKI, JAQUELINA; CRAVO, SERGIO L.; NERY, LUIZ E.; STICKLAND, MICHAEL K.; et al. Cardiac baroreflex dysfunction in patients with pulmonary arterial hypertension at rest and during orthostatic stress: role of the peripheral chemoreflex. Journal of Applied Physiology, v. 131, n. 2, p. 794-807, AUG 2021. (16/01155-6, 15/22198-2, 16/23622-5, 14/24294-6)

PAULA-RIBEIRO, MARCELLE; RIBEIRO, INDYANARA C.; ARANDA, LILIANE; SILVA, TALITA M.; COSTA, CAMILA M.; RAMOS, ROBERTA P.; ARAKAKI, JAQUELINA O.; CRAVO, SERGIO L.; NERY, LUIZ E.; STICKLAND, MICHAEL K.; et al. Peripheral Chemoreflex Regulates Post-exercise Cardiac Vagal Reactivation in Healthy Humans and Patients with Pulmonary Arterial Hypertension. FASEB JOURNAL, v. 31, p. 2-pg., 2017-04-01. (14/24294-6, 15/22198-2)