Pyridostigmine Improves the Effects of Resistance Exercise Training after Myocardial Infarction in Rats

Abstract

Myocardial infarction (MI) remains the leading cause of morbidity and mortality worldwide. Exercise training and pharmacological treatments are important strategies to minimize the deleterious effects of MI. However, little is known about the effects of resistance training combined with pyridostigmine bromide (PYR) treatment on cardiac and autonomic function, as well as on the inflammatory profile after MI. Thus, in the present study, male Wistar rats were randomly assigned into: control (Cont); sedentary infarcted (Inf); PYR – treated sedentary infarcted rats (Inf+P); infarcted rats undergoing resistance exercise training (Inf+RT); and infarcted rats undergoing PYR treatment plus resistance training (Inf+RT+P). After 12 weeks of resistance training (15–20 climbs per session, with a 1-min rest between each climb, at a low to moderate intensity, 5 days a week) and/or PYR treatment (0.14 mg/mL of drink water), hemodynamic function, autonomic modulation, and cytokine expressions were evaluated. We observed that 3 months of PYR treatment, either alone or in combination with exercise, can improve the deleterious effects of MI on left ventricle dimensions and function, baroreflex sensitivity, and autonomic parameters, as well as systemic and tissue inflammatory profile. Furthermore, additional benefits in a maximal load test and anti-inflammatory state of skeletal muscle were found when resistance training was combined with PYR treatment. Thus, our findings suggest that the combination of resistance training and PYR may be a good therapeutic strategy since they promote additional benefits on skeletal muscle anti-inflammatory profile after MI.

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

“…31,33,35,37,38 ACh from cholinergic nerve ending inhibits noradrenaline release by activation of muscarinic receptors near presynaptic sympathetic nerve terminals, thereby attenuating sympathetic activity. 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. 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.…”

“…103 In the same way, donepezil enhanced the survival pathway through increasing the pAkt/Akt ratio, leading to improved cardiac function and survival of chronic heart failure mice. 27,31,32,37,38 However, there are inconsistencies as some reports demonstrate that AChE inhibitors may not attenuate infarct size after MI. 105 As infarct size plays an important role in cardiac remodelling and function, 106 it is promising that AChE inhibitors have been shown to attenuate infarct size and cardiac dysfunction in various models.…”

“…39 In that study, donepezil was added to losartan (ARB) and this combination decreased neurohumoral activation and adverse cardiac remodelling, improved cardiac function and increased survival in rats with heart failure compared to losartan alone. 37,38 In heart failure rats, aerobic exercise training combined with pyridostigmine improved sympathovagal balance, and reduced infarct size and inflammation compared to aerobic exercise training alone. 39 In addition, several reports demonstrated that exercise training to modulate vagal activity could provide greater efficacy when added to treatment with an AChE inhibitor as shown in experimental studies of heart failure.…”

“…21 However, further clinical studies are needed to warrant its clinical use. [26][27][28][29][30][31][32][33][34][35][36][37][38][39] Despite its potential clinical benefits for CVDs patients, the role of AChE inhibitors in AMI and heart failure remediation remains unclear. 22,23 Use of AChE inhibitors is a non-invasive intervention which increases the parasympathetic activity.…”