Abstract

The mechanisms regulating immune cells recruitment into the heart during healing after an acute myocardial infarction (AMI) have major clinical implications. We investigated whether cholinergic stimulation with pyridostigmine, a cholinesterase inhibitor, modulates heart and spleen immune responses and cardiac remodeling after AMI in spontaneous hypertensive rats (SHRs). Male adult SHRs underwent sham surgery or ligation of the left coronary artery and were randomly allocated to remain untreated or to pyridostigmine treatment (40 mg/kg once a day by gavage). Blood pressure and heart rate variability were determined, and echocardiography was performed at day six after MI. The heart and spleen were processed for immunohistochemistry cellular analyses (CD3+ and CD4+ lymphocytes, and CD68+ and CD206+ macrophages), and TNF levels were determined at day seven after MI. Pyridostigmine treatment increased the parasympathetic tone and T CD4+ lymphocytes in the myocardium, but lowered M1/M2 macrophage ratio towards an anti-inflammatory profile that was associated with decreased TNF levels in the heart and spleen. Treatment with this cholinergic agent improved heart remodeling manifested by lower ventricular diameters and better functional parameters. In summary, cholinergic stimulation by pyridostigmine enhances the parasympathetic tone and induces anti-inflammatory responses in the heart and spleen fostering cardiac recovery after AMI in SHRs.

Details

Title
Cholinergic stimulation with pyridostigmine modulates a heart-spleen axis after acute myocardial infarction in spontaneous hypertensive rats
Author
Bandoni Robson Luiz 1 ; Bricher Choque Pamela Nithzi 1 ; Dellê Humberto 1 ; de Moraes Tercio Lemos 1 ; Porter Maria Helena Mattos 1 ; da Silva Bruno Durante 2 ; Neves, Gizele Alves 1 ; Maria-Claudia, Irigoyen 2 ; De Angelis Kátia 3 ; Pavlov, Valentin A 4 ; Ulloa, Luis 5 ; Consolim-Colombo, Fernanda Marciano 6 

 Universidade Nove de Julho (UNINOVE), Biotechnology Laboratory, Postgraduate Program in Medicine, São Paulo, Brazil (GRID:grid.412295.9) (ISNI:0000 0004 0414 8221) 
 Medical School of University of São Paulo, Hypertension Unit, Heart Institute (INCOR), São Paulo, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722) 
 Universidade Nove de Julho (UNINOVE), Biotechnology Laboratory, Postgraduate Program in Medicine, São Paulo, Brazil (GRID:grid.412295.9) (ISNI:0000 0004 0414 8221); Federal University of São Paulo (UNIFESP), Departament of Physiology, São Paulo, Brazil (GRID:grid.411249.b) (ISNI:0000 0001 0514 7202) 
 Northwell Health, Feinstein Institutes for Medical Research, Manhasset, USA (GRID:grid.416477.7) (ISNI:0000 0001 2168 3646) 
 Duke University Medical Center, Department of Anesthesiology, Durham, USA (GRID:grid.189509.c) (ISNI:0000000100241216) 
 Universidade Nove de Julho (UNINOVE), Biotechnology Laboratory, Postgraduate Program in Medicine, São Paulo, Brazil (GRID:grid.412295.9) (ISNI:0000 0004 0414 8221); Medical School of University of São Paulo, Hypertension Unit, Heart Institute (INCOR), São Paulo, Brazil (GRID:grid.11899.38) (ISNI:0000 0004 1937 0722) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2522237290
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.