Evidence for the cardiodepressive effects of the plasticizer di-2-ethylhexylphthalate (DEHP)

Authors

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

Document Type

Journal Article

Publication Date

10-9-2023

Journal

Toxicological sciences : an official journal of the Society of Toxicology

DOI

10.1093/toxsci/kfad105

Keywords

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

Abstract

Di-2-ethylhexylphthalate (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 (RBC) units stored between 7-42 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 prolonged by 56.5% following 30-minute 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, and increased incidence of atrioventricular uncoupling. Pretreatment with doxycycline partially rescued the effects of DEHP on sinus activity, but did not ameliorate the effects on atrioventricular 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 (hiPSC-CM) confirmed that DEHP slows electrical conduction in a time (15 min-3 hours) 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-ethylhexyl phthalate (MEHP). 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-ethylhexylphthalate (DEHP)" (2023). GW Authored Works. Paper 3625.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/3625

Department

Pediatrics