Impacto da piridostigmina no eixo cardio-esplênico após infarto agudo do miocárdio em ratos espontaneamente hipertensos (SHR)

Abstract

INTRODUCTION: The inflammatory process in response to acute myocardial infarction (AMI) is essential for local tissue repair. However, this process is not restricted to the injured area, and occurs at a systemic level. When it is insufficient or excessive, the patient can progress with serious complications. Previous work has shown that the autonomic nervous system modulates the local and systemic inflammatory response in models of septic and aseptic inflammation. In particular, stimulation of the vagus nerve reduces inflammation, the so-called anti-inflammatory cholinergic reflex. In this circuit, the spleen and the subpopulation of resident lymphocytes that are producers of acetylcholine (ChAT+ lymphocytes) are fundamental components for the anti-inflammatory response. Despite its importance, there is little information about the variation in the number of ChAT+ lymphocytes in the spleen after AMI and the ability of cholinergic stimulation to modulate this response. OBJECTIVE: To analyze the effects of the administration of the anticholinesterase Piridostigmine bromide on hemodynamic, autonomic and morphofunctional parameters of the heart, and on the number of ChAT+ lymphocytes in the spleen of spontaneously hypertensive rats (SHR) submitted to AMI by ligation of the left coronary artery. METHODS: Initially, the animals were divided into a control group (submitted to thoracotomy - Sham), an untreated infarcted group (AMI), and an infarcted group treated with Piridostigmine (40 mg / kg / day, administered by gavage - AMI + PI). On the sixth day of follow-up, all animals underwent invasive blood pressure curves (femoral artery cannulation) to obtain hemodynamic parameters and quantify heart rate variability, and an echo Doppler cardiogram. On the seventh day the animals were euthanized, and the spleen was collected and prepared for immunohistochemistry for ChAT+ lymphocytes; cell counting followed an established protocol and was performed on specific equipment. All variables were presented as means and standard deviations. For comparison between groups, one-way ANOVA was used followed by Bonferroni's post hoc test, and p <0.05 was considered statistically significant. RESULTS: When compared to the SHAM group, the infarcted group (AMI) showed a reduction in systolic (≅ 30 mmHg) and diastolic (≅ 18 mmHg) blood pressure; similar heart rate; increased sympathetic modulation and reduced vagal activity; with increased BF / AF ratio (0.2); increased size and reduced left ventricular systolic (-16.6%) and diastolic function; and increased population of ChAT+ lymphocytes in the spleen (260). The group that received PI (AMI + PI), compared to the AMI group, did not have differences in hemodynamic parameters, however, they showed a significant increase in vagal activity (19.9) and a reduction in the BF / AF ratio (0.1), reduction in size and improvement in left ventricular diastolic function. In addition, no significant difference was observed in the number of ChAT+ lymphocytes in the spleen. CONCLUSION: the administration of PI, for a short period of time after AMI, improves sympathovagal modulation and has a positive impact on cardiac remodeling, without altering the number of ChAT+ lymphocytes in the spleen, in the evaluated time.