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Effect of acetylcholinesterase inhibition on connexin 43 preservation in the heart of rats with acute myocardial infarction

Grant number: 13/26217-6
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): June 01, 2014
Effective date (End): December 05, 2016
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Rubens Fazan Junior
Grantee:Fernanda Machado Santos de Almeida
Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):15/08931-9 - The effect of acetylcholinesterase inhibition on preservation of connexin 43 degradation in cardomyocytes subjected to ischemia and ischemia/reperfusion condition, BE.EP.PD


Acute myocardial infarction (MI) is a major health problem due to its high incidence and mortality. The MI is always accompanied by a dysautonomia characterized by sympathetic overactivity and decreased cardiac vagal tone. Life threatening cardiac arrhythmias are commonly seen in patients with MI. It is consensual, and the issue of intense research, that sympathetic hyperactivity is deleterious and a risk factor to serious arrhythmias and sudden death in patients with MI. However, lower cardiac vagal activity has been considered an independent cardiovascular risk factor in MI. Among the major causes of cardiac arrhythmias is the electrical instability of cardiomyocytes caused by the deterioration of membrane proteins responsible for maintaining the integrity of gap junctions present in cardiac tissue.Evidences point to an anti-arrhythmic property of cardiac vagal activity, since the use of parasympathomimetic agents, or electrical stimulation of the vagus nerve, reduces the incidence of arrhythmias caused by MI. Furthermore, it has been shown that cholinergic stimulation prevents the degradation of connexin 43 (Cx43), the most important protein of gap junctions. This study aims to evaluate the effect of acute blockade of acetylcholinesterase by pyridostigmine (PYR) in the degradation of Cx43 protein elicited by MI.Young adult male rats under isoflurane anesthesia, will undergo surgical ligation of the left coronary artery to elicit extensive MI. Following, infarcted rats will receive PYR (0.25 mg/kg, iv) or vehicle (saline). After 4 hours, the rats will be killed (overdose of anesthetic) and will have the hearts removed. Part of animals will be subjected to an electrocardiogram (ECG) recording and monitoring for a period of 4 hours. The heart tissue will be homogenized and appropriately processed to quantify fosforilated and total Cx43 by Western blot. The proteins of the pathways of degradation of Cx43 (ubiquitin - proteasome and autophagy) will also be analyzed in cardiac homogenates of infarcted rats. Tissue expression of Cx43 (immunohistochemistry) will also be assessed in separate groups of infarcted rats, treated or not with PYR. The project also aims to evaluate the effect of PYR in preventing in vitro degradation of Cx43 caused by culture media poor in oxygen and nutrients. (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)
SANTOS-ALMEIDA, FERNANDA MACHADO; DOMINGOS-SOUZA, GEAN; MESCHIARI, CESAR A.; FAVARO, LAURA CAMPOS; BECARI, CHRISTIANE; CASTANIA, JACI A.; LOPES, ALEXANDRE; CUNHA, THIAGO M.; MORAES, DAVI J. A.; CUNHA, FERNANDO Q.; et al. Carotid sinus nerve electrical stimulation in conscious rats attenuates systemic inflammation via chemoreceptor activation. SCIENTIFIC REPORTS, v. 7, . (13/06452-0, 13/20549-7, 11/20343-4, 13/26217-6, 13/13269-8)

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