Pyridostigmine restores cardiac autonomic balance after small myocardial infarction in mice

• Published in: PloS one 2014-08, Vol.9 (8), p.e104476-e104476
• Main Authors: Durand, Marina T, Becari, Christiane, de Oliveira, Mauro, do Carmo, Jussara M, Silva, Carlos Alberto Aguiar, Prado, Cibele M, Fazan, Jr, Rubens, Salgado, Helio C
• Format: Article
• Language: English
• Subjects: Acetylcholine; Acetylcholinesterase; Anesthesia; Animals; Atropine; Autonomic nervous system; Biology and Life Sciences; Blood Pressure; Cardiotonic Agents - administration & dosage; Cardiovascular disease; Cardiovascular system; Carotid artery; Cholinesterase Inhibitors - administration & dosage; Coronary artery; Coronary vessels; Drug Evaluation, Preclinical; Heart attack; Heart attacks; Heart diseases; Heart failure; Heart rate; Hemodynamics; Implantation; Infarction; Infusions, Subcutaneous; Isoflurane; Male; Medicine; Medicine and Health Sciences; Mice; Mice, Inbred C57BL; Myocardial infarction; Myocardial Infarction - drug therapy; Myocardial Infarction - physiopathology; Myocardium - pathology; Parasympathetic nervous system; Pharmacology; Phosphorylation; Physiology; Propranolol; Pyridostigmine; Pyridostigmine Bromide - administration & dosage; Rodents; Surgery; Sympathetic nervous system; Tachycardia; Telemetry; Transmitters; Vagus nerve; Ventricular Function, Left - drug effects
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0104476

The effect of pyridostigmine (PYR)--an acetylcholinesterase inhibitor--on hemodynamics and cardiac autonomic control, was never studied in conscious myocardial infarcted mice. Telemetry transmitters were implanted into the carotid artery under isoflurane anesthesia. Seven to ten days after recovery from the surgery, basal arterial pressure and heart rate were recorded, while parasympathetic and sympathetic tone (ΔHR) was evaluated by means of methyl atropine and propranolol. After the basal hemodynamic recording the mice were subjected to left coronary artery ligation for producing myocardial infarction (MI), or sham operation, and implantation of minipumps filled with PYR or saline. Separate groups of anesthetized (isoflurane) mice previously (4 weeks) subjected to MI, or sham coronary artery ligation, were submitted to cardiac function examination. The mice exhibited an infarct length of approximately 12%, no change in arterial pressure and increased heart rate only in the 1st week after MI. Vagal tone decreased in the 1st week, while the sympathetic tone was increased in the 1st and 4th week after MI. PYR prevented the increase in heart rate but did not affect the arterial pressure. Moreover, PYR prevented the increase in sympathetic tone throughout the 4 weeks. Concerning the parasympathetic tone, PYR not only impaired its attenuation in the 1st week, but enhanced it in the 4th week. MI decreased ejection fraction and increased diastolic and systolic volume. Therefore, the pharmacological increase of peripheral acetylcholine availability by means of PYR prevented tachycardia, increased parasympathetic and decreased sympathetic tone after MI in mice.