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.

Figure 1

Systolic function evaluated by echocardiogram. Two-way ANOVA with Bonferroni posttest. (A) EF – ejection fraction; (B) FS – fractional shortening. *P < 0.05 vs. C; ^†P < 0.05 vs. I.

Figure 2

(A) Baroreflex sensitivity evaluated by tachycardic and bradycardic responses. (B) Sympathetic tone. (C) Vagal tone. *P < 0.05 vs. C; ^†P < 0.05 vs. I.

Figure 3

Serum inflammatory markers. (A) IL-6. (B) IL-10. *P < 0.05 vs. C; ^†P < 0.05 vs. I.

Figure 4

Inflammatory markers on the left ventricle. (A) IFN-γ. (B) IL-6. (C) IL-1β. (D) TNF-α. (E) IL-10. (F) IL-10/ TNF-α. *P < 0.05 vs. C; ^†P < 0.05 vs. I.

Figure 5

Inflammatory markers on white adipose tissue. (A) IFN-γ. (B) IL-6. (C) IL-1β. (D) TNF-α. (E) IL-10. (F) IL-10/ TNF-α. *P < 0.05 vs. C; ^†P < 0.05 vs. I.