Cholinergic Stimulation by Pyridostigmine Bromide Before Myocardial Infarction Prevent Cardiac and Autonomic Dysfunction

Abstract

Inflammatory processes and cardiovascular autonomic imbalance are very relevant characteristic of the enormous dynamic process that is a myocardial infarction (MI). In this sense, some studies are investigating pharmacological therapies using acetylcholinesterase inhibitors, such as pyridostigmine bromide (PYR), aiming to increase parasympathetic tone after MI. Here we hypothesized that the use of PYR before the MI might bring an additional positive effect to the autonomic function, and consequently, in the inflammatory response and cardiac function. The present study aimed to evaluate left ventricular function, baroreflex sensitivity, autonomic modulation, and inflammatory profile in PYR-treated rats previously to MI. Methods: Male Wistar rats (250–300 g) were treated for 60 days with PYR. After treatment, they were submitted to the MI. After the MI, the autonomic and ventricular function were evaluated, as well as the systemic, left ventricle, and adipose tissue inflammatory profile. Results: PYR, performed before MI, prevented HR increase, systolic function impairment, baroreflex sensitivity drop, as well as pulse interval variance, RMSSD, blood pressure and parasympathetic modulation reduction in treated rats compared to untreated rats. Also, this positive functional changes may have been a result of the reduced inflammatory parameters in the left ventricle (IFN-γ, IL-6, and IL-1β), as well as increased IL-10 expression and IL-10/TNF-α ratio in treated animals before MI. Conclusion: Prior treatment with PYR prevents impairment of the autonomic nervous system after MI, which may be associated with the attenuated expression of inflammatory factors and heart dysfunction.

The effects of acetylcholinesterase inhibitors on the heart in acute myocardial infarction and heart failure: From cells to patient reports

“…The reduction of the LF/HF ratio indicated increased parasympathetic activity and led to improved heart rate variability in MI rats. 28,30,31,36,38,56 Similarly, pyridostigmine increased baroreflex sensitivity in MI rats. 31,35,37,38,56 All these reported benefits could contribute to attenuating the severity of MI.…”

“…14 Use of an AChE inhibitor has been shown to improve cardiac autonomic balance by increasing parasympathetic tone and suppressing sympathetic tone in rats with MI. 13,36,[54][55][56] Heart rate variability is an indirect method that is used to determine cardiac autonomic function. 53 Several studies reported that AChE inhibitors suppress neurohumoral activation and sympathetic tone, thus improving cardiac autonomic function and cardiac remodelling in MI rats.…”

“…13,36,[54][55][56] Heart rate variability is an indirect method that is used to determine cardiac autonomic function. 31,35,37,38,56 All these reported benefits could contribute to attenuating the severity of MI. 57 AChE inhibitors increased the HF component, while decreasing the LF and LF/ HF ratio.…”

“…53 Several studies reported that AChE inhibitors suppress neurohumoral activation and sympathetic tone, thus improving cardiac autonomic function and cardiac remodelling in MI rats. 13,36,[54][55][56] Heart rate variability is an indirect method that is used to determine cardiac autonomic function. It has been shown that the high frequency (HF) component is a marker of parasympathetic tone, whereas the low frequency (LF) component is considered a marker of sympathetic and parasympathetic activity.…”

“…84 Numerous studies have shown that AChE inhibitors diminished inflammation in MI and other CVDs, resulting in attenuated cardiac remodelling and dysfunction. 13,27,28,30,37,38,56 Wound healing after MI, however, is a dynamic event which is both time and cell type-dependent. 85 Innate and adaptive immune cells are involved in initiating the wound healing process.…”