{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T05:31:41Z","timestamp":1784179901017,"version":"3.55.0"},"reference-count":77,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circ: Arrhythmia and Electrophysiology"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              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\n              <jats:sub>v<\/jats:sub>\n              1.5 (874 and 231 \u00b5mol\/L half-maximal inhibitory concentration, fast and late sodium current).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>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\u2014given that action potential triangulation and electrical restitution modifications are a risk factor for early after depolarizations and cardiac arrhythmias.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circep.119.007294","type":"journal-article","created":{"date-parts":[[2019,6,28]],"date-time":"2019-06-28T09:00:23Z","timestamp":1561712423000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":52,"title":["Plasticizer Interaction With the Heart"],"prefix":"10.1161","volume":"12","author":[{"suffix":"III","given":"Rafael","family":"Jaimes","sequence":"first","affiliation":[{"name":"Sheikh Zayed Institute for Pediatric Surgical Innovation (R.J., D. McCullough, L.S., D. McInerney, J.H., N.G.P.), Children\u2019s National Health System, Washington DC."},{"name":"Children\u2019s National Heart Institute (R.J., B.S., L.S., N.G.P.), Children\u2019s National Health System, Washington DC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Damon","family":"McCullough","sequence":"additional","affiliation":[{"name":"Sheikh Zayed Institute for Pediatric Surgical Innovation (R.J., D. McCullough, L.S., D. McInerney, J.H., N.G.P.), Children\u2019s National Health System, Washington DC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan","family":"Siegel","sequence":"additional","affiliation":[{"name":"Children\u2019s National Heart Institute (R.J., B.S., L.S., N.G.P.), Children\u2019s National Health System, Washington DC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luther","family":"Swift","sequence":"additional","affiliation":[{"name":"Sheikh Zayed Institute for Pediatric Surgical Innovation (R.J., D. McCullough, L.S., D. McInerney, J.H., N.G.P.), Children\u2019s National Health System, Washington DC."},{"name":"Children\u2019s National Heart Institute (R.J., B.S., L.S., N.G.P.), Children\u2019s National Health System, Washington DC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"McInerney","sequence":"additional","affiliation":[{"name":"Sheikh Zayed Institute for Pediatric Surgical Innovation (R.J., D. McCullough, L.S., D. McInerney, J.H., N.G.P.), Children\u2019s National Health System, Washington DC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Hiebert","sequence":"additional","affiliation":[{"name":"Sheikh Zayed Institute for Pediatric Surgical Innovation (R.J., D. McCullough, L.S., D. McInerney, J.H., N.G.P.), Children\u2019s National Health System, Washington DC."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick A.","family":"Perez-Alday","sequence":"additional","affiliation":[{"name":"Knight Cardiovascular Institute, Oregon Health and Science University, Portland (E.A.P.-A., L.G.T.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Trenor","sequence":"additional","affiliation":[{"name":"Ci2B-Universitat Polit\u00e8cnica de Val\u00e8ncia, Spain (B.T., F.J.S.R.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiansong","family":"Sheng","sequence":"additional","affiliation":[{"name":"CiPA Lab, LLC, Rockville, MD (J.S.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Saiz","sequence":"additional","affiliation":[{"name":"Sheikh Zayed Institute for Pediatric Surgical Innovation (R.J., D. McCullough, L.S., D. 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