Sympathetic nerve innervation and metabolism in ischemic myocardium in response to remote ischemic perconditioning

Sympathetic nerve denervation after myocardial infarction (MI) predicts risk of sudden cardiac death. Therefore, therapeutic approaches limit infarct size, improving adverse remodeling and restores sympathetic innervation have a great clinical potential. Remote ischemic perconditioning (RIPerc) coul...

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Autores principales: Kiss, Attila, Wu, Ping, Schlederer, Michaela, Pilz, Patrick M., Szabo, Petra Lujza, Li, Jingle, Weber, Lukas, Vraka, Chrysoula, Pichler, Verena, Mitterhauser, Markus, Zhang, Xiaoli, Zins, Karin, Abraham, Dietmar, Li, Sijin, Podesser, Bruno K., Hacker, Marcus, Li, Xiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411095/
https://www.ncbi.nlm.nih.gov/pubmed/36008727
http://dx.doi.org/10.1007/s00395-022-00946-3
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author Kiss, Attila
Wu, Ping
Schlederer, Michaela
Pilz, Patrick M.
Szabo, Petra Lujza
Li, Jingle
Weber, Lukas
Vraka, Chrysoula
Pichler, Verena
Mitterhauser, Markus
Zhang, Xiaoli
Zins, Karin
Abraham, Dietmar
Li, Sijin
Podesser, Bruno K.
Hacker, Marcus
Li, Xiang
author_facet Kiss, Attila
Wu, Ping
Schlederer, Michaela
Pilz, Patrick M.
Szabo, Petra Lujza
Li, Jingle
Weber, Lukas
Vraka, Chrysoula
Pichler, Verena
Mitterhauser, Markus
Zhang, Xiaoli
Zins, Karin
Abraham, Dietmar
Li, Sijin
Podesser, Bruno K.
Hacker, Marcus
Li, Xiang
author_sort Kiss, Attila
collection PubMed
description Sympathetic nerve denervation after myocardial infarction (MI) predicts risk of sudden cardiac death. Therefore, therapeutic approaches limit infarct size, improving adverse remodeling and restores sympathetic innervation have a great clinical potential. Remote ischemic perconditioning (RIPerc) could markedly attenuate MI-reperfusion (MIR) injury. In this study, we aimed to assess its effects on cardiac sympathetic innervation and metabolism. Transient myocardial ischemia is induced by ligature of the left anterior descending coronary artery (LAD) in male Sprague–Dawley rats, and in vivo cardiac 2-[(18)F]FDG and [(11)C]mHED PET scans were performed at 14–15 days after ischemia. RIPerc was induced by three cycles of 5-min-long unilateral hind limb ischemia and intermittent 5 min of reperfusion during LAD occlusion period. The PET quantitative parameters were quantified in parametric polar maps. This standardized format facilitates the regional radioactive quantification in deficit regions to remote areas. The ex vivo radionuclide distribution was additionally identified using autoradiography. Myocardial neuron density (tyrosine hydroxylase positive staining) and chondroitin sulfate proteoglycans (CSPG, inhibiting neuron regeneration) expression were assessed by immunohistochemistry. There was no significant difference in the mean hypometabolism 2-[(18)F]FDG uptake ratio (44.6 ± 4.8% vs. 45.4 ± 4.4%) between MIR rats and MIR + RIPerc rats (P > 0.05). However, the mean [(11)C]mHED nervous activity of denervated myocardium was significantly elevated in MIR + RIPerc rats compared to the MIR rats (35.9 ± 7.1% vs. 28.9 ± 2.3%, P < 0.05), coupled with reduced denervated myocardium area (19.5 ± 5.3% vs. 27.8 ± 6.6%, P < 0.05), which were associated with preserved left-ventricular systolic function, a less reduction in neuron density, and a significant reduction in CSPG and CD68 expression in the myocardium. RIPerc presented a positive effect on cardiac sympathetic-nerve innervation following ischemia, but showed no significant effect on myocardial metabolism.
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spelling pubmed-94110952022-08-27 Sympathetic nerve innervation and metabolism in ischemic myocardium in response to remote ischemic perconditioning Kiss, Attila Wu, Ping Schlederer, Michaela Pilz, Patrick M. Szabo, Petra Lujza Li, Jingle Weber, Lukas Vraka, Chrysoula Pichler, Verena Mitterhauser, Markus Zhang, Xiaoli Zins, Karin Abraham, Dietmar Li, Sijin Podesser, Bruno K. Hacker, Marcus Li, Xiang Basic Res Cardiol Original Contribution Sympathetic nerve denervation after myocardial infarction (MI) predicts risk of sudden cardiac death. Therefore, therapeutic approaches limit infarct size, improving adverse remodeling and restores sympathetic innervation have a great clinical potential. Remote ischemic perconditioning (RIPerc) could markedly attenuate MI-reperfusion (MIR) injury. In this study, we aimed to assess its effects on cardiac sympathetic innervation and metabolism. Transient myocardial ischemia is induced by ligature of the left anterior descending coronary artery (LAD) in male Sprague–Dawley rats, and in vivo cardiac 2-[(18)F]FDG and [(11)C]mHED PET scans were performed at 14–15 days after ischemia. RIPerc was induced by three cycles of 5-min-long unilateral hind limb ischemia and intermittent 5 min of reperfusion during LAD occlusion period. The PET quantitative parameters were quantified in parametric polar maps. This standardized format facilitates the regional radioactive quantification in deficit regions to remote areas. The ex vivo radionuclide distribution was additionally identified using autoradiography. Myocardial neuron density (tyrosine hydroxylase positive staining) and chondroitin sulfate proteoglycans (CSPG, inhibiting neuron regeneration) expression were assessed by immunohistochemistry. There was no significant difference in the mean hypometabolism 2-[(18)F]FDG uptake ratio (44.6 ± 4.8% vs. 45.4 ± 4.4%) between MIR rats and MIR + RIPerc rats (P > 0.05). However, the mean [(11)C]mHED nervous activity of denervated myocardium was significantly elevated in MIR + RIPerc rats compared to the MIR rats (35.9 ± 7.1% vs. 28.9 ± 2.3%, P < 0.05), coupled with reduced denervated myocardium area (19.5 ± 5.3% vs. 27.8 ± 6.6%, P < 0.05), which were associated with preserved left-ventricular systolic function, a less reduction in neuron density, and a significant reduction in CSPG and CD68 expression in the myocardium. RIPerc presented a positive effect on cardiac sympathetic-nerve innervation following ischemia, but showed no significant effect on myocardial metabolism. Springer Berlin Heidelberg 2022-08-25 2022 /pmc/articles/PMC9411095/ /pubmed/36008727 http://dx.doi.org/10.1007/s00395-022-00946-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Contribution
Kiss, Attila
Wu, Ping
Schlederer, Michaela
Pilz, Patrick M.
Szabo, Petra Lujza
Li, Jingle
Weber, Lukas
Vraka, Chrysoula
Pichler, Verena
Mitterhauser, Markus
Zhang, Xiaoli
Zins, Karin
Abraham, Dietmar
Li, Sijin
Podesser, Bruno K.
Hacker, Marcus
Li, Xiang
Sympathetic nerve innervation and metabolism in ischemic myocardium in response to remote ischemic perconditioning
title Sympathetic nerve innervation and metabolism in ischemic myocardium in response to remote ischemic perconditioning
title_full Sympathetic nerve innervation and metabolism in ischemic myocardium in response to remote ischemic perconditioning
title_fullStr Sympathetic nerve innervation and metabolism in ischemic myocardium in response to remote ischemic perconditioning
title_full_unstemmed Sympathetic nerve innervation and metabolism in ischemic myocardium in response to remote ischemic perconditioning
title_short Sympathetic nerve innervation and metabolism in ischemic myocardium in response to remote ischemic perconditioning
title_sort sympathetic nerve innervation and metabolism in ischemic myocardium in response to remote ischemic perconditioning
topic Original Contribution
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9411095/
https://www.ncbi.nlm.nih.gov/pubmed/36008727
http://dx.doi.org/10.1007/s00395-022-00946-3
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