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Importance of reinstating respiratory sinus arrhythmia for cardiac function in cardiovascular diseases

Grant number: 12/24095-8
Support Opportunities:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): June 01, 2013
Effective date (End): May 31, 2014
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Helio Cesar Salgado
Grantee:Renata Maria Lataro
Supervisor: Julian Francis Richmond Paton
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Research place: University of Bristol, England  
Associated to the scholarship:11/12460-0 - Effects of acetylcholinesterase blockade, central and peripheral, in the cardiocirculatory function and inflammation observed in spontaneously hypertensive rats, BP.PD


Respiratory sinus arrhythmia (RSA) is a cardiorespiratory phenomenon characterized in mammals by heart rate (HR) fluctuations in phase with respiratory inhalation and exhalation. Typically, HR accelerates during inspiration and slows down during expiration. However, the functional significance of the RSA remains controversial. RSA is lost in both heart failure (HF) and hypertension and is a prognostic index for sudden cardiac death. The absence of RSA may increase myocardial oxygen consumption and reduces the diastolic period, thereby decreasing the time for coronary perfusion. In coronary heart disease, where a reduction of coronary blood flow and oxygen supply already exist, the absence of RSA may affect the adequate tissue oxygenation turning the myocardium susceptible to episodes of hypoxia. We propose that the reestablishment of the RSA in these pathological conditions will improve the coronary blood flow, producing beneficial effects on the cardiac function. Recently, it was demonstrated in rats that the RSA can be augmented by stimulating the vagus nerve in phase with phrenic nerve activity, by means of a central pattern generator. It remains unknown whether such a device would correct the RSA in animal models of human cardiovascular disease providing therapeutic benefit. Therefore, we propose to examine the functional contribution of the RSA in the regulation of the coronary blood flow in healthy rats, and test whether reinstating the RSA in animal models of human cardiovascular diseases, such as arterial hypertension and HF, improves the cardiac function and autonomic modulation combined with an anti-inflammatory effect. The HF will be induced by myocardial infarction in Wistar rats. Initially, the coronary blood flow will be evaluated with the use of fluorescent microspheres in awake spontaneously hypertensive rats (SHR) and Wistar HF rats. The blockade of muscarinic receptors with atropine will be used to evaluate the influence of the vagal tone on the coronary blood flow. Therefore, it will be evaluated the effect of the reestablishment of the ASR in SHR and Wistar HF rats on: 1) the basal coronary blood flow; 2) the variability of pulse interval and blood pressure; 3) cardiac function; 4) plasma concentration of cytokines: IL-1±, IL-², IL-6, IL-10, IL-17, IL-23, TNF-±, IFN-³; 5) the infiltration of T lymphocytes, T lymphocytes and dendritic cells regulator in the heart, aorta, brain and kidney. The ASR will be reinstated by a generator of electrical stimulation of central pattern which receives stimuli from the phrenic nerve and produces voltage fluctuations used to stimulate the vagus, producing HR reduction in phase with the expiration. It is expected that the ASR will play a role in the maintenance of the physiological levels of coronary blood flow, improving the outcomes of cardiovascular diseases (hypertension or HF), such as the deteriorated cardiac function, the reduced cardiovascular autonomic modulation and the augmented systemic inflammation. (AU)

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