Cholinergic stimulation with pyridostigmine protects myocardial infarcted rats against ischemic-induced arrhythmias and preserves connexin43 protein

Abstract

We investigated the effects of acute pyridostigmine (PYR) treatment, an acetylcholinesterase inhibitor, on arterial pressure (AP), heart rate (HR), cardiac sympathovagal balance, and the incidence of arrhythmias during the first 4 h after myocardial infarction (MI) in anesthetized rats. Male Wistar rats were implanted with catheters into the femoral artery and vein for AP recordings and drug administration. Rats received the autonomic receptor blockers methyl-atropine (1 mg/kg iv) and propranolol (2 mg/kg iv) at intervals of 15 min, 1 h after saline ( n = 16) or PYR (0.25 mg/kg iv, n = 18), to indirectly assess sympathovagal balance. Acute treatment with PYR increased cardiac vagal (86 ± 7 vs. 44 ± 5 beats/min) and decreased sympathetic tone (−31 ± 8 vs. −69 ± 7 beats/min). Different animals were implanted with ECG electrodes and catheters. A large MI was induced via left coronary artery ligation after basal recordings. Rats received PYR ( n = 14) or saline ( n = 14) 10–15 min after MI, and the recordings lasted up to 4 h. In part of the animals, hearts were removed for connexin43 quantification after all procedures. MI elicited a fall in AP (−45 ± 5 mmHg), a progressive rise in HR (26 ± 14 beats/min), and an increase in corrected QT interval (33 ± 13 ms). PYR elicited a prompt bradycardia (−50 ± 14 beats/min) that returned to basal levels over time, and it prevented the lengthening of the corrected QT interval. Treatment with PYR increased by ∼20% the occurrence of rats free of arrhythmias after MI. MI markedly decreased connexin43 in left ventricles, and PYR treatment partially prevented this decrease.