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Vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow

Vagal nerve stimulation (VNS) started prior to, or during, ischemia has been shown to reduce infarct size. Here, we investigated the effect of VNS when started just prior to, and continued during early, reperfusion on infarct size and no-reflow and studied the underlying mechanisms. For this purpose...

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Autores principales: Uitterdijk, André, Yetgin, Tuncay, te Lintel Hekkert, Maaike, Sneep, Stefan, Krabbendam-Peters, Ilona, van Beusekom, Heleen M. M., Fischer, Trent M., Cornelussen, Richard N., Manintveld, Olivier C., Merkus, Daphne, Duncker, Dirk J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549380/
https://www.ncbi.nlm.nih.gov/pubmed/26306761
http://dx.doi.org/10.1007/s00395-015-0508-3
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author Uitterdijk, André
Yetgin, Tuncay
te Lintel Hekkert, Maaike
Sneep, Stefan
Krabbendam-Peters, Ilona
van Beusekom, Heleen M. M.
Fischer, Trent M.
Cornelussen, Richard N.
Manintveld, Olivier C.
Merkus, Daphne
Duncker, Dirk J.
author_facet Uitterdijk, André
Yetgin, Tuncay
te Lintel Hekkert, Maaike
Sneep, Stefan
Krabbendam-Peters, Ilona
van Beusekom, Heleen M. M.
Fischer, Trent M.
Cornelussen, Richard N.
Manintveld, Olivier C.
Merkus, Daphne
Duncker, Dirk J.
author_sort Uitterdijk, André
collection PubMed
description Vagal nerve stimulation (VNS) started prior to, or during, ischemia has been shown to reduce infarct size. Here, we investigated the effect of VNS when started just prior to, and continued during early, reperfusion on infarct size and no-reflow and studied the underlying mechanisms. For this purpose, swine (13 VNS, 10 sham) underwent 45 min mid-LAD occlusion followed by 120 min of reperfusion. VNS was started 5 min prior to reperfusion and continued until 15 min of reperfusion. Area at risk, area of no-reflow (% of infarct area) and infarct size (% of area at risk), circulating cytokines, and regional myocardial leukocyte influx were assessed after 120 min of reperfusion. VNS significantly reduced infarct size from 67 ± 2 % in sham to 54 ± 5 % and area of no-reflow from 54 ± 6 % in sham to 32 ± 6 %. These effects were accompanied by reductions in neutrophil (~40 %) and macrophage (~60 %) infiltration in the infarct area (all p < 0.05), whereas systemic circulating plasma levels of TNFα and IL6 were not affected. The degree of cardioprotection could not be explained by the VNS-induced bradycardia or the VNS-induced decrease in the double product of heart rate and left ventricular systolic pressure. In the presence of NO-synthase inhibitor LNNA, VNS no longer attenuated infarct size and area of no-reflow, which was paralleled by similarly unaffected regional leukocyte infiltration. In conclusion, VNS is a promising novel adjunctive therapy that limits reperfusion injury in a large animal model of acute myocardial infarction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00395-015-0508-3) contains supplementary material, which is available to authorized users.
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spelling pubmed-45493802015-08-27 Vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow Uitterdijk, André Yetgin, Tuncay te Lintel Hekkert, Maaike Sneep, Stefan Krabbendam-Peters, Ilona van Beusekom, Heleen M. M. Fischer, Trent M. Cornelussen, Richard N. Manintveld, Olivier C. Merkus, Daphne Duncker, Dirk J. Basic Res Cardiol Original Contribution Vagal nerve stimulation (VNS) started prior to, or during, ischemia has been shown to reduce infarct size. Here, we investigated the effect of VNS when started just prior to, and continued during early, reperfusion on infarct size and no-reflow and studied the underlying mechanisms. For this purpose, swine (13 VNS, 10 sham) underwent 45 min mid-LAD occlusion followed by 120 min of reperfusion. VNS was started 5 min prior to reperfusion and continued until 15 min of reperfusion. Area at risk, area of no-reflow (% of infarct area) and infarct size (% of area at risk), circulating cytokines, and regional myocardial leukocyte influx were assessed after 120 min of reperfusion. VNS significantly reduced infarct size from 67 ± 2 % in sham to 54 ± 5 % and area of no-reflow from 54 ± 6 % in sham to 32 ± 6 %. These effects were accompanied by reductions in neutrophil (~40 %) and macrophage (~60 %) infiltration in the infarct area (all p < 0.05), whereas systemic circulating plasma levels of TNFα and IL6 were not affected. The degree of cardioprotection could not be explained by the VNS-induced bradycardia or the VNS-induced decrease in the double product of heart rate and left ventricular systolic pressure. In the presence of NO-synthase inhibitor LNNA, VNS no longer attenuated infarct size and area of no-reflow, which was paralleled by similarly unaffected regional leukocyte infiltration. In conclusion, VNS is a promising novel adjunctive therapy that limits reperfusion injury in a large animal model of acute myocardial infarction. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00395-015-0508-3) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2015-08-26 2015 /pmc/articles/PMC4549380/ /pubmed/26306761 http://dx.doi.org/10.1007/s00395-015-0508-3 Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Contribution
Uitterdijk, André
Yetgin, Tuncay
te Lintel Hekkert, Maaike
Sneep, Stefan
Krabbendam-Peters, Ilona
van Beusekom, Heleen M. M.
Fischer, Trent M.
Cornelussen, Richard N.
Manintveld, Olivier C.
Merkus, Daphne
Duncker, Dirk J.
Vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow
title Vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow
title_full Vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow
title_fullStr Vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow
title_full_unstemmed Vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow
title_short Vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow
title_sort vagal nerve stimulation started just prior to reperfusion limits infarct size and no-reflow
topic Original Contribution
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4549380/
https://www.ncbi.nlm.nih.gov/pubmed/26306761
http://dx.doi.org/10.1007/s00395-015-0508-3
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