Plasticizer Interaction With the Heart

Rafael Jaimes, Damon McCullough, Bryan Siegel, Luther Swift, Daniel McInerney, James Hiebert, Erick A. Perez-Alday, Beatriz Trenor, Jiansong Sheng, Javier Saiz, Larisa Tereshchenko, Nikki Gillum Posnack

    Research output: Contribution to journalArticle

    1 Citation (Scopus)

    Abstract

    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 Nav1.5 (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.

    Original languageEnglish (US)
    Pages (from-to)e007294
    JournalCirculation. Arrhythmia and electrophysiology
    Volume12
    Issue number7
    DOIs
    StatePublished - Jul 1 2019

    Fingerprint

    Plasticizers
    Action Potentials
    Cardiac Electrophysiology
    Plastics
    Safety
    Atrioventricular Node
    Critical Care
    mono-(2-ethylhexyl)phthalate
    Cardiac Arrhythmias
    Sodium
    Equipment and Supplies

    Keywords

    • action potentials
    • electrophysiology
    • heart
    • plasticizer
    • plastics

    ASJC Scopus subject areas

    • Cardiology and Cardiovascular Medicine
    • Physiology (medical)

    Cite this

    Jaimes, R., McCullough, D., Siegel, B., Swift, L., McInerney, D., Hiebert, J., ... Posnack, N. G. (2019). Plasticizer Interaction With the Heart. Circulation. Arrhythmia and electrophysiology, 12(7), e007294. https://doi.org/10.1161/CIRCEP.119.007294

    Plasticizer Interaction With the Heart. / Jaimes, Rafael; McCullough, Damon; Siegel, Bryan; Swift, Luther; McInerney, Daniel; Hiebert, James; Perez-Alday, Erick A.; Trenor, Beatriz; Sheng, Jiansong; Saiz, Javier; Tereshchenko, Larisa; Posnack, Nikki Gillum.

    In: Circulation. Arrhythmia and electrophysiology, Vol. 12, No. 7, 01.07.2019, p. e007294.

    Research output: Contribution to journalArticle

    Jaimes, R, McCullough, D, Siegel, B, Swift, L, McInerney, D, Hiebert, J, Perez-Alday, EA, Trenor, B, Sheng, J, Saiz, J, Tereshchenko, L & Posnack, NG 2019, 'Plasticizer Interaction With the Heart', Circulation. Arrhythmia and electrophysiology, vol. 12, no. 7, pp. e007294. https://doi.org/10.1161/CIRCEP.119.007294
    Jaimes R, McCullough D, Siegel B, Swift L, McInerney D, Hiebert J et al. Plasticizer Interaction With the Heart. Circulation. Arrhythmia and electrophysiology. 2019 Jul 1;12(7):e007294. https://doi.org/10.1161/CIRCEP.119.007294
    Jaimes, Rafael ; McCullough, Damon ; Siegel, Bryan ; Swift, Luther ; McInerney, Daniel ; Hiebert, James ; Perez-Alday, Erick A. ; Trenor, Beatriz ; Sheng, Jiansong ; Saiz, Javier ; Tereshchenko, Larisa ; Posnack, Nikki Gillum. / Plasticizer Interaction With the Heart. In: Circulation. Arrhythmia and electrophysiology. 2019 ; Vol. 12, No. 7. pp. e007294.
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    abstract = "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 Nav1.5 (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.",
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    AU - Jaimes, Rafael

    AU - McCullough, Damon

    AU - Siegel, Bryan

    AU - Swift, Luther

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    AU - Hiebert, James

    AU - Perez-Alday, Erick A.

    AU - Trenor, Beatriz

    AU - Sheng, Jiansong

    AU - Saiz, Javier

    AU - Tereshchenko, Larisa

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    N2 - 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 Nav1.5 (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.

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