Evidence for the cardiodepressive effects of the plasticizer di-2-ethylhexyl phthalate

Authors

Luther M. Swift, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, District of Columbia 20010, USA.
Anysja Roberts, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, District of Columbia 20010, USA.
Jenna Pressman, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, District of Columbia 20010, USA.
Devon Guerrelli, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, District of Columbia 20010, USA.
Samuel Allen, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, District of Columbia 20010, USA.
Kazi T. Haq, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, District of Columbia 20010, USA.
Julie A. Reisz, Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, USA.
Angelo D'Alessandro, Department of Biochemistry and Molecular Genetics, University of Colorado, Anschutz Medical Campus, Aurora, Colorado 80045, USA.
Nikki Gillum Posnack, Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, District of Columbia 20010, USA.

Document Type

Journal Article

Publication Date

12-21-2023

Journal

Toxicological sciences : an official journal of the Society of Toxicology

Volume

197

Issue

1

DOI

10.1093/toxsci/kfad105

Keywords

DEHP; Langendorff; cardiac electrophysiology; hiPSC-CM; phthalate

Abstract

Di-2-ethylhexyl phthalate (DEHP) is commonly used in the manufacturing of plastic materials, including intravenous bags, blood storage bags, and medical-grade tubing. DEHP can leach from plastic medical products, which can result in inadvertent patient exposure. DEHP concentrations were measured in red blood cell units stored between 7 and 42 days (17-119 μg/ml). Using these concentrations as a guide, Langendorff-perfused rat heart preparations were acutely exposed to DEHP. Sinus activity remained stable with lower doses of DEHP (25-50 μg/ml), but sinus rate declined by 43% and sinus node recovery time (SNRT) prolonged by 56.5% following 30-min exposure to 100 μg/ml DEHP. DEHP exposure also exerted a negative dromotropic response, as indicated by a 69.4% longer PR interval, 108.5% longer Wenckebach cycle length (WBCL), and increased incidence of atrioventricular (AV) uncoupling (60-min exposure). Pretreatment with doxycycline partially rescued the effects of DEHP on sinus activity, but did not ameliorate the effects on AV conduction. DEHP exposure also prolonged the ventricular action potential and effective refractory period, but had no measurable effect on intracellular calcium transient duration. Follow-up studies using human-induced pluripotent stem cell-derived cardiomyocytes confirmed that DEHP slows electrical conduction in a time (15 min-3 h) and dose-dependent manner (10-100 μg/ml). Previous studies have suggested that phthalate toxicity is specifically attributed to metabolites of DEHP, including mono-2-ethylhexylphthalate. This study demonstrates that DEHP exposure also contributes to cardiac dysfunction in a dose- and time-dependent manner. Future work is warranted to investigate the impact of DEHP (and its metabolites) on human health, with special consideration for clinical procedures that employ plastic materials.

APA Citation

Swift, Luther M.; Roberts, Anysja; Pressman, Jenna; Guerrelli, Devon; Allen, Samuel; Haq, Kazi T.; Reisz, Julie A.; D'Alessandro, Angelo; and Posnack, Nikki Gillum, "Evidence for the cardiodepressive effects of the plasticizer di-2-ethylhexyl phthalate" (2023). GW Authored Works. Paper 3933.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3933

Department

Pediatrics