We previously reported that cholinergic stimulation with pyridostigmine (PY) induces anti-inflammatory cell recruitment soon after myocardial infarction (MI). In this study, we evaluated the anti-inflammatory effects of PY during the proliferative phase of cardiac repair by analyzing the infiltration of macrophages, Treg lymphocytes, oxidative stress and inflammatory cytokines. Wistar rats underwent control sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated (untreated infarcted group, I) or to receive PY (30 mg·kg(−1)·day(−1)) in the supplied water (infarcted treated group, I + PY). Blood pressure and heart rate variability were registered at day 5 post-MI. The animals were euthanized 7 days after thoracotomy, when the hearts were removed and processed for immunohistochemistry (CD68, CD206, FOXP3), cytokines (IL-1β, IL-6, IL-10, TNF-α) and oxidative stress (superoxide dismutase, catalase, glutathione peroxidase, lipidic and protein peroxidation). PY treatment increased parasympathetic modulation, M2 macrophages and the anti-oxidant enzyme activity but reduced protein oxidation (carbonyls) and the concentration of IL-1β, IL-6, TNF-α and IL-10. Cholinergic stimulation induces parasympathetic neuro-immune modulation and anti-inflammatory cell enrollment as well as prevents oxidative stress and cytokine production after MI.

-We tested the hypothesis that an increase in the anti-inflammatory cholinergic pathway, when induced by pyridostigmine (PY), may modulate subtypes of lymphocytes (CD4ϩ, CD8ϩ, FOXP3ϩ) and macrophages (M1/M2) soon after myocardial infarction (MI) in rats. Wistar rats, randomly allocated to receive PY (40 mg·kg Ϫ1 ·day Ϫ1 ) in drinking water or to stay without treatment, were followed for 4 days and then were subjected to ligation of the left coronary artery. The groupsdenominated as the pyridostigmine-treated infarcted (IP) and infarcted control (I) groups-were submitted to euthanasia 3 days after MI; the heart was removed for immunohistochemistry, and the peripheral blood and spleen were collected for flow cytometry analysis. Noninfarcted and untreated rats were used as controls (C Group). Echocardiographic measurements were registered on the second day after MI, and heart rate variability was measured on the third day after MI. The infarcted groups had similar MI areas, degrees of systolic dysfunction, blood pressures, and heart rates. Compared with the I Group, the IP Group showed a significant higher parasympathetic modulation and a lower sympathetic modulation, which were associated with a small, but significant, increase in diastolic function. The IP Group showed a significant increase in M2 macrophages and FOXP3 ϩ cells in the infarcted and peri-infarcted areas, a significantly higher frequency of circulating Treg cells (CD4 ϩ CD25 ϩ FOXP3 ϩ ), and a less extreme decrease in conventional T cells (CD25 ϩ FOXP3 Ϫ ) compared with the I Group. Therefore, increasing cholinergic modulation with PY induces greater anti-inflammatory cell recruitment soon after MY in rats. myocardial infarction; T lymphocytes; macrophage activation; anticholinesterase drugs; cholinergic anti-inflammatory reflex

The cardiovascular autonomic imbalance in patients after myocardial infarction (MI) provides a significant increase in mortality rate, and seems to precede metabolic, hormonal, and immunological changes. Moreover, the reduction in the parasympathetic function has been associated with inflammatory response in different pathological conditions. Over the years, most of the studies have indicated the exercise training (ET) as an important nonpharmacological tool in the management of autonomic dysfunction and reduction in inflammatory profile after a myocardial infarction. In this work, we reviewed the effects of ET on autonomic imbalance after MI, and its consequences, particularly, in the post-MI inflammatory profile. Clinical and experimental evidence regarding relationship between alterations in autonomic regulation and local or systemic inflammation response after MI were also discussed.

The presence of asymptomatic LVDD is associated with increased MSNA, independent of blood pressure control. The sympathetic hyperactivity associated with LVDD is similar in the different patterns of LVDD studied.

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