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Plasticizer Interaction With the Heart: Chemicals Used in Plastic Medical Devices Can Interfere With Cardiac Electrophysiology
BACKGROUND: Phthalates are used as plasticizers in the manufacturing of flexible, plastic medical products. Patients can be subjected to high phthalate exposure through contact with plastic medical devices. We aimed to investigate the cardiac safety and biocompatibility of mono-2-ethylhexyl phthalat...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Lippincott Williams & Wilkins
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693678/ https://www.ncbi.nlm.nih.gov/pubmed/31248280 http://dx.doi.org/10.1161/CIRCEP.119.007294 |
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author | Jaimes, Rafael McCullough, Damon Siegel, Bryan Swift, Luther McInerney, Daniel Hiebert, James Perez-Alday, Erick A. Trenor, Beatriz Sheng, Jiansong Saiz, Javier Tereshchenko, Larisa G Posnack, Nikki Gillum |
author_facet | Jaimes, Rafael McCullough, Damon Siegel, Bryan Swift, Luther McInerney, Daniel Hiebert, James Perez-Alday, Erick A. Trenor, Beatriz Sheng, Jiansong Saiz, Javier Tereshchenko, Larisa G Posnack, Nikki Gillum |
author_sort | Jaimes, Rafael |
collection | PubMed |
description | BACKGROUND: Phthalates are used as plasticizers in the manufacturing of flexible, plastic medical products. Patients can be subjected to high phthalate exposure through contact with plastic medical devices. We aimed to investigate the cardiac safety and biocompatibility of mono-2-ethylhexyl phthalate (MEHP), a phthalate with documented exposure in intensive care patients. METHODS: Optical mapping of transmembrane voltage and pacing studies were performed on isolated, Langendorff-perfused rat hearts to assess cardiac electrophysiology after MEHP exposure compared with controls. MEHP dose was chosen based on reported blood concentrations after an exchange transfusion procedure. RESULTS: Thirty-minute exposure to MEHP increased the atrioventricular node (147 versus 107 ms) and ventricular (117 versus 77.5 ms) effective refractory periods, compared with controls. Optical mapping revealed prolonged action potential duration at slower pacing cycle lengths, akin to reverse use dependence. The plateau phase of the action potential duration restitution curve steepened and became monophasic in MEHP-exposed hearts (0.18 versus 0.06 slope). Action potential duration lengthening occurred during late-phase repolarization resulting in triangulation (70.3 versus 56.6 ms). MEHP exposure also slowed epicardial conduction velocity (35 versus 60 cm/s), which may be partly explained by inhibition of Na(v)1.5 (874 and 231 µmol/L half-maximal inhibitory concentration, fast and late sodium current). CONCLUSIONS: This study highlights the impact of acute MEHP exposure, using a clinically relevant dose, on cardiac electrophysiology in the intact heart. Heightened clinical exposure to plasticized medical products may have cardiac safety implications—given that action potential triangulation and electrical restitution modifications are a risk factor for early after depolarizations and cardiac arrhythmias. |
format | Online Article Text |
id | pubmed-6693678 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Lippincott Williams & Wilkins |
record_format | MEDLINE/PubMed |
spelling | pubmed-66936782020-07-01 Plasticizer Interaction With the Heart: Chemicals Used in Plastic Medical Devices Can Interfere With Cardiac Electrophysiology Jaimes, Rafael McCullough, Damon Siegel, Bryan Swift, Luther McInerney, Daniel Hiebert, James Perez-Alday, Erick A. Trenor, Beatriz Sheng, Jiansong Saiz, Javier Tereshchenko, Larisa G Posnack, Nikki Gillum Circ Arrhythm Electrophysiol Original Articles BACKGROUND: Phthalates are used as plasticizers in the manufacturing of flexible, plastic medical products. Patients can be subjected to high phthalate exposure through contact with plastic medical devices. We aimed to investigate the cardiac safety and biocompatibility of mono-2-ethylhexyl phthalate (MEHP), a phthalate with documented exposure in intensive care patients. METHODS: Optical mapping of transmembrane voltage and pacing studies were performed on isolated, Langendorff-perfused rat hearts to assess cardiac electrophysiology after MEHP exposure compared with controls. MEHP dose was chosen based on reported blood concentrations after an exchange transfusion procedure. RESULTS: Thirty-minute exposure to MEHP increased the atrioventricular node (147 versus 107 ms) and ventricular (117 versus 77.5 ms) effective refractory periods, compared with controls. Optical mapping revealed prolonged action potential duration at slower pacing cycle lengths, akin to reverse use dependence. The plateau phase of the action potential duration restitution curve steepened and became monophasic in MEHP-exposed hearts (0.18 versus 0.06 slope). Action potential duration lengthening occurred during late-phase repolarization resulting in triangulation (70.3 versus 56.6 ms). MEHP exposure also slowed epicardial conduction velocity (35 versus 60 cm/s), which may be partly explained by inhibition of Na(v)1.5 (874 and 231 µmol/L half-maximal inhibitory concentration, fast and late sodium current). CONCLUSIONS: This study highlights the impact of acute MEHP exposure, using a clinically relevant dose, on cardiac electrophysiology in the intact heart. Heightened clinical exposure to plasticized medical products may have cardiac safety implications—given that action potential triangulation and electrical restitution modifications are a risk factor for early after depolarizations and cardiac arrhythmias. Lippincott Williams & Wilkins 2019-07 2019-06-28 /pmc/articles/PMC6693678/ /pubmed/31248280 http://dx.doi.org/10.1161/CIRCEP.119.007294 Text en © 2019 The Authors. Circulation: Arrhythmia and Electrophysiology is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited, the use is noncommercial, and no modifications or adaptations are made. |
spellingShingle | Original Articles Jaimes, Rafael McCullough, Damon Siegel, Bryan Swift, Luther McInerney, Daniel Hiebert, James Perez-Alday, Erick A. Trenor, Beatriz Sheng, Jiansong Saiz, Javier Tereshchenko, Larisa G Posnack, Nikki Gillum Plasticizer Interaction With the Heart: Chemicals Used in Plastic Medical Devices Can Interfere With Cardiac Electrophysiology |
title | Plasticizer Interaction With the Heart: Chemicals Used in Plastic Medical Devices Can Interfere With Cardiac Electrophysiology |
title_full | Plasticizer Interaction With the Heart: Chemicals Used in Plastic Medical Devices Can Interfere With Cardiac Electrophysiology |
title_fullStr | Plasticizer Interaction With the Heart: Chemicals Used in Plastic Medical Devices Can Interfere With Cardiac Electrophysiology |
title_full_unstemmed | Plasticizer Interaction With the Heart: Chemicals Used in Plastic Medical Devices Can Interfere With Cardiac Electrophysiology |
title_short | Plasticizer Interaction With the Heart: Chemicals Used in Plastic Medical Devices Can Interfere With Cardiac Electrophysiology |
title_sort | plasticizer interaction with the heart: chemicals used in plastic medical devices can interfere with cardiac electrophysiology |
topic | Original Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693678/ https://www.ncbi.nlm.nih.gov/pubmed/31248280 http://dx.doi.org/10.1161/CIRCEP.119.007294 |
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