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Intracoronary Poloxamer 188 Prevents Reperfusion Injury in a Porcine Model of ST-Segment Elevation Myocardial Infarction
Poloxamer 188 (P188) is a nonionic triblock copolymer believed to prevent cellular injury after ischemia and reperfusion. This study compared intracoronary (IC) infusion of P188 immediately after reperfusion with delayed infusion through a peripheral intravenous catheter in a porcine model of ST-seg...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042154/ https://www.ncbi.nlm.nih.gov/pubmed/27695713 http://dx.doi.org/10.1016/j.jacbts.2016.04.001 |
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author | Bartos, Jason A. Matsuura, Timothy R. Tsangaris, Adamantios Olson, Matthew McKnite, Scott H. Rees, Jennifer N. Haman, Karen Shekar, Kadambari Chandra Riess, Matthias L. Bates, Frank S. Metzger, Joseph M. Yannopoulos, Demetris |
author_facet | Bartos, Jason A. Matsuura, Timothy R. Tsangaris, Adamantios Olson, Matthew McKnite, Scott H. Rees, Jennifer N. Haman, Karen Shekar, Kadambari Chandra Riess, Matthias L. Bates, Frank S. Metzger, Joseph M. Yannopoulos, Demetris |
author_sort | Bartos, Jason A. |
collection | PubMed |
description | Poloxamer 188 (P188) is a nonionic triblock copolymer believed to prevent cellular injury after ischemia and reperfusion. This study compared intracoronary (IC) infusion of P188 immediately after reperfusion with delayed infusion through a peripheral intravenous catheter in a porcine model of ST-segment elevation myocardial infarction (STEMI). STEMI was induced in 55 pigs using 45 min of endovascular coronary artery occlusion. Pigs were then randomized to 4 groups: control, immediate IC P188, delayed peripheral P188, and polyethylene glycol infusion. Heart tissue was collected after 4 h of reperfusion. Assessment of mitochondrial function or infarct size was performed. Mitochondrial yield improved significantly with IC P188 treatment compared with control animals (0.25% vs. 0.13%), suggesting improved mitochondrial morphology and survival. Mitochondrial respiration and calcium retention were also significantly improved with immediate IC P188 compared with control animals (complex I respiratory control index: 7.4 vs. 3.7; calcium retention: 1,152 nmol vs. 386 nmol). This benefit was only observed with activation of complex I of the mitochondrial respiratory chain, suggesting a specific effect from ischemia and reperfusion on this complex. Infarct size and serum troponin I were significantly reduced by immediate IC P188 infusion (infarct size: 13.9% vs. 41.1%; troponin I: 19.2 μg/l vs. 77.4 μg/l). Delayed P188 and polyethylene glycol infusion did not provide a significant benefit. These results demonstrate that intracoronary infusion of P188 immediately upon reperfusion significantly reduces cellular and mitochondrial injury after ischemia and reperfusion in this clinically relevant porcine model of STEMI. The timing and route of delivery were critical to achieve the benefit. |
format | Online Article Text |
id | pubmed-5042154 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-50421542016-09-29 Intracoronary Poloxamer 188 Prevents Reperfusion Injury in a Porcine Model of ST-Segment Elevation Myocardial Infarction Bartos, Jason A. Matsuura, Timothy R. Tsangaris, Adamantios Olson, Matthew McKnite, Scott H. Rees, Jennifer N. Haman, Karen Shekar, Kadambari Chandra Riess, Matthias L. Bates, Frank S. Metzger, Joseph M. Yannopoulos, Demetris JACC Basic Transl Sci PRE-CLINICAL RESEARCH Poloxamer 188 (P188) is a nonionic triblock copolymer believed to prevent cellular injury after ischemia and reperfusion. This study compared intracoronary (IC) infusion of P188 immediately after reperfusion with delayed infusion through a peripheral intravenous catheter in a porcine model of ST-segment elevation myocardial infarction (STEMI). STEMI was induced in 55 pigs using 45 min of endovascular coronary artery occlusion. Pigs were then randomized to 4 groups: control, immediate IC P188, delayed peripheral P188, and polyethylene glycol infusion. Heart tissue was collected after 4 h of reperfusion. Assessment of mitochondrial function or infarct size was performed. Mitochondrial yield improved significantly with IC P188 treatment compared with control animals (0.25% vs. 0.13%), suggesting improved mitochondrial morphology and survival. Mitochondrial respiration and calcium retention were also significantly improved with immediate IC P188 compared with control animals (complex I respiratory control index: 7.4 vs. 3.7; calcium retention: 1,152 nmol vs. 386 nmol). This benefit was only observed with activation of complex I of the mitochondrial respiratory chain, suggesting a specific effect from ischemia and reperfusion on this complex. Infarct size and serum troponin I were significantly reduced by immediate IC P188 infusion (infarct size: 13.9% vs. 41.1%; troponin I: 19.2 μg/l vs. 77.4 μg/l). Delayed P188 and polyethylene glycol infusion did not provide a significant benefit. These results demonstrate that intracoronary infusion of P188 immediately upon reperfusion significantly reduces cellular and mitochondrial injury after ischemia and reperfusion in this clinically relevant porcine model of STEMI. The timing and route of delivery were critical to achieve the benefit. Elsevier 2016-05-13 /pmc/articles/PMC5042154/ /pubmed/27695713 http://dx.doi.org/10.1016/j.jacbts.2016.04.001 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | PRE-CLINICAL RESEARCH Bartos, Jason A. Matsuura, Timothy R. Tsangaris, Adamantios Olson, Matthew McKnite, Scott H. Rees, Jennifer N. Haman, Karen Shekar, Kadambari Chandra Riess, Matthias L. Bates, Frank S. Metzger, Joseph M. Yannopoulos, Demetris Intracoronary Poloxamer 188 Prevents Reperfusion Injury in a Porcine Model of ST-Segment Elevation Myocardial Infarction |
title | Intracoronary Poloxamer 188 Prevents Reperfusion Injury in a Porcine Model of ST-Segment Elevation Myocardial Infarction |
title_full | Intracoronary Poloxamer 188 Prevents Reperfusion Injury in a Porcine Model of ST-Segment Elevation Myocardial Infarction |
title_fullStr | Intracoronary Poloxamer 188 Prevents Reperfusion Injury in a Porcine Model of ST-Segment Elevation Myocardial Infarction |
title_full_unstemmed | Intracoronary Poloxamer 188 Prevents Reperfusion Injury in a Porcine Model of ST-Segment Elevation Myocardial Infarction |
title_short | Intracoronary Poloxamer 188 Prevents Reperfusion Injury in a Porcine Model of ST-Segment Elevation Myocardial Infarction |
title_sort | intracoronary poloxamer 188 prevents reperfusion injury in a porcine model of st-segment elevation myocardial infarction |
topic | PRE-CLINICAL RESEARCH |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5042154/ https://www.ncbi.nlm.nih.gov/pubmed/27695713 http://dx.doi.org/10.1016/j.jacbts.2016.04.001 |
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