Abstract P240: Acetylcholine Stimulation with Pyridostigmine Prevents Cardiac Arrhythmias in Conscious Myocardial Infarcted Rats and Upregulate Connexin 43, Hipoxic Inducible Factor-1α and Vascular Endothelial Grow Factor in Cardiomyocytes Culture

Abstract

Objective: To examine the impact on hemodynamics and electrocardiogram (ECG) of treating acutely infarcted rats with the acetylcholinesterase inhibitor pyridostigmine (PYR). We also examined the effect of PYR on connexin 43 (Cx43), an important protein for the ventricular cell to cell communication; on hypoxic inducible factor (HIF-1α), a transcriptional factor related to cell survival pathways under hypoxia, and on vascular endothelial grow factor (VEGF) in cultured cardiomyocytes subjected to ischemia-mimetic conditions. Methods and Results: Wistar rats, previously implanted with ECG electrodes and catheters into femoral artery and vein were subjected, under inhaled anesthesia, to coronary artery ligation to elicit MI, and after 20 min they received PYR (0.12 mg/kg iv, N=8) or saline (N=7). After 3h, the animals had their arterial pressure (AP) and ECG recorded for 60 min. Additionally, H9c2 cells were incubated with PYR (0.5 mM) during 1h before being subjected to the ischemia-mimetic solution during 1h. Mean AP was found similar between groups (94±5 vs. 90±3 mmHg) while heart rate (HR) was lower in rats treated with PYR (390±11 vs. 441±12 bpm). The number of premature ectopic beats was markedly lower in rats that received PYR, as compared to saline treated counterparts (median: 7 vs. 27, 25 th percentile: 1.75 vs. 8.5 and 75 th percentile: 17 vs. 166). In cultured cells incubated with PYR Cx43 was found higher (0.72±0,16 vs. 0.49±0,16), as well as HIF-1α (3.88±0.41 vs. 2.23±0.5), and mRNA for VEGF (qualitative analysis). Conclusion: Treatment with PYR showed positive effects, reducing the tachycardia and arrhythmias commonly seen after acute MI. Additionally, PYR affected proteins related to cell communication, cell surviving and vascular grow in cultured cardiomyocytes subjected to ischemia-mimetic conditions. The in vitro effects of PYR might be linked to its beneficial effects observed in infarcted rats. In another view, the results open a very new field of cholinergic role on cardiomyocytes to be further investigated.