Abstract 472: Effect of Acetylcholinesterase Inhibition with Pyridostigmine on Hemodynamics, Autonomic and Cardiac Function in Heart Failure C57Bl/6J Mice.
We investigated the effects of pyridostigmine (PYR) on hemodynamics, autonomic and cardiac function in heart failure (HF) mice. Telemetry transmitters (DSI) were implanted into the carotid artery under isofluorane anesthesia. After recovery, basal arterial pressure (AP, mmHg) and heart rate (HR, bpm) were recorded and parasympathetic and sympathetic tone (Δbpm) was evaluated by means of methyl atropine and propranolol. After the basal recording, the mice were submitted to left coronary ligation (LCL) and mini pumps implantation (PYR: 3mg/kg/day). Control mice were implanted with empty mini pumps. One and four weeks after LCL, the recordings were repeated. LCL promoted a myocardial infarction of 10-20%. HF mice presented decreased systolic AP (SAP) (113±2 vs 120±2 basal) and increased HR (548±12 vs 489±20 basal) only in the 1st week (n=8). In addition, LCL decreased vagal tone in the 1st week (121±14 vs 177±9 basal), increased sympathetic tone in the 1st and 4th week (-41±6 and -49±10 vs -23±2 basal). PYR prevented the increase of HR (505±10 vs 495±7 basal) but did not affect the decrease of the SAP (113±3 vs 123±1 basal) in the 1st week (n=3). PYR prevented the increase in the sympathetic tone (-23±15 and -23±6 vs -17±10 basal), but did not affect the parasympathetic tone (218±30 vs 199±37 basal) throughout the study. Cardiac function was assessed in separated mice (n=23) under isofluorane anesthesia. HF mice exhibited a decreased ejection fraction (28±4 vs 45±1% sham LCL) and increased diastolic and systolic volume (31±2 and 24±3 vs 18±2 and 12±1μl sham LCL). PYR increased the ejection fraction (44±4%) and attenuated the increase of both volumes (24±4 and 14±3μl). In conclusion, PYR prevented the tachycardia, decreased sympathetic tone and protected the cardiac function during the development (4 weeks) of HF in mice.
- © 2012 by American Heart Association, Inc.