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Title: Increase in parasympathetic tone by pyridostigmine prevents ventricular dysfunction during the onset of heart failure
Authors: Lataro, Renata M.
Silva, Carlos A. A.
Fazan, Rubens
Rossi, Marcos A.
Prado, Cibele M.
Godinho, Rosely O. [UNIFESP]
Salgado, Helio C.
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
Keywords: vagal stimulation
anticholinesterase agent
cardiac function
cardiac remodeling
autonomic imbalance
Issue Date: 1-Oct-2013
Publisher: Amer Physiological Soc
Citation: American Journal of Physiology-regulatory Integrative and Comparative Physiology. Bethesda: Amer Physiological Soc, v. 305, n. 8, p. R908-R916, 2013.
Abstract: Heart failure (HF) is characterized by elevated sympathetic activity and reduced parasympathetic control of the heart. Experimental evidence suggests that the increase in parasympathetic function can be a therapeutic alternative to slow HF evolution. the parasympathetic neurotransmission can be improved by acetylcholinesterase inhibition. We investigated the long-term (4 wk) effects of the acetylcholinesterase inhibitor pyridostigmine on sympathovagal balance, cardiac remodeling, and cardiac function in the onset of HF following myocardial infarction. Myocardial infarction was elicited in adult male Wistar rats. After 4 wk of pyridostigmine administration, per os, methylatropine and propranolol were used to evaluate the cardiac sympathovagal balance. the tachycardic response caused by methylatropine was considered to be the vagal tone, whereas the bradycardic response caused by propranolol was considered to be the sympathetic tone. in conscious HF rats, pyridostigmine reduced the basal heart rate, increased vagal, and reduced sympathetic control of heart rate. Pyridostigmine reduced the myocyte diameter and collagen density of the surviving left ventricle. Pyridostigmine also increased vascular endothelial growth factor protein in the left ventricle, suggesting myocardial angiogenesis. Cardiac function was assessed by means of the pressure-volume conductance catheter system. HF rats treated with pyridostigmine exhibited a higher stroke volume, ejection fraction, cardiac output, and contractility of the left ventricle. It was demonstrated that the long-term administration of pyridostigmine started right after coronary artery ligation augmented cardiac vagal and reduced sympathetic tone, attenuating cardiac remodeling and left ventricular dysfunction during the progression of HF in rats.
ISSN: 0363-6119
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