Reduction of QTc interval dispersion. Potential mechanism of cardiac protection of pyridostigmine bromide

Abstract

Objective -Parasympathetic dysfunction is an independent risk factor in individuals with (PR segment, QT interval, QTc, and QT dispersion). Conclusion -Bradycardia and the reduction in

Acute electrophysiologic consequences of pyridostigmine inhibition of cholinesterase in humans

“…Therefore, pyridostigmine presents a potential anti-arrhythmic effect at higher heart rates, as occurs during physical exercise and mental stress. Accordingly, previous studies have shown a modulatory action of pyridostigmine on cardiovascular reactivity to exercise and stress, both in healthy subjects (18) and in patients with cardiovascular diseases (13,14,19). Whether adverse outcomes can be hampered by pyridostigmine or the sustained release version of the drug leads to a better effective action with lower side affects remains to be determined.…”

“…Studies including healthy volunteers and patients with cardiovascular disease have shown that pyridostigmine shifts the autonomic balance to parasympathetic dominance and may reduce arrhythmia density (14,17,29). A single dose of pyridostigmine elicited bradycardia and reduced QTc dispersion in healthy young subjects (18). When administered to patients with coronary artery disease, pyridostigmine reduced the QTc interval at rest (29) and its recovery from maximal effort (14).…”

“…Albeit exhibiting promising effects, edrophonium needs to be administered intravenously, precluding its prescription for regular use. Therefore, pyridostigmine, which can be administered orally and causes a dose-dependent vagomimetic effect with few side effects (13)(14)(15)(16)(17)(18)(19), is a preferable candidate for the treatment of impaired parasympathetic modulation in heart disease. As a drug that elicits a parasympathetic effect, pyridostigmine was expected to cause bradycardia in the present study.…”

“…In addition, it has been shown to counteract the adverse anti-cholinergic effects of disopyramide, such as decreased baseline saliva and tear production (12). We have previously shown that short-term administration of pyridostigmine may be also potentially useful for cardiovascular protection since in healthy individuals and patients with cardiovascular diseases it results in beneficial effects on markers of cardiovascular risk and dysfunction (8,(13)(14)(15)(16)(17)(18)(19).…”

“…In patients with coronary artery disease, pyridostigmine improves the autonomic and hemodynamic responses to exercise (13,14,19), prevents the myocardial dysfunction induced by mental stress (16), and reduces QTc dispersion (18). In a randomized, crossover, placebo-controlled, and double-blind study, pyridostigmine administration increased heart rate variability and reduced ventricular arrhythmia density in patients with heart failure (17), an effect mediated, at least in part, by stimulation of the endogenous nitric oxide pathway (20).…”