Evidence for the cardiodepressive effects of the plasticizer di-2-ethylhexyl phthalate.
Level 5 - mechanism / opinion, no new human data
Bench research using ex vivo Langendorff-perfused rat hearts and in vitro human iPSC-derived cardiomyocytes.
PubMed 37812252 · doi:10.1093/toxsci/kfad105
What was done
DEHP concentrations were measured in clinical red blood cell units stored for 7 to 42 days (range 17–119 µg/ml). Langendorff-perfused rat hearts were acutely exposed to DEHP (25–100 µg/ml) to assess sinus activity, atrioventricular (AV) conduction, ventricular action potentials, effective refractory period, and intracellular calcium transients, with or without doxycycline pretreatment. Follow-up electrophysiological testing was conducted in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exposed to 10–100 µg/ml DEHP for 15 minutes to 3 hours.
What was found
In rat hearts, exposure to 100 µg/ml DEHP for 30 minutes reduced sinus rate by 43% and prolonged sinus node recovery time by 56.5% (25–50 µg/ml had stable sinus activity). A 60-minute exposure prolonged the PR interval by 69.4%, lengthened the Wenckebach cycle length by 108.5%, and increased AV uncoupling. Doxycycline partially rescued sinus activity but did not improve AV conduction. DEHP lengthened ventricular action potential duration and effective refractory period without altering calcium transient duration. In hiPSC-CMs, DEHP caused time- and dose-dependent slowing of electrical conduction across 10–100 µg/ml.
Why it matters
Plasticizer toxicity is often attributed to downstream metabolites, but this study shows that the parent compound DEHP directly impairs cardiac electrophysiology at concentrations found in routinely stored blood products.
Limits
The abstract does not state the sample sizes for rat hearts or cell culture replicates. Findings are derived entirely from isolated animal tissue and in vitro human cells, lacking intact in vivo hemodynamics, autonomic regulation, and systemic metabolic clearance.
Cited by
- context In rodent studies, exposure to the phthalate metabolite DBP decreases coronary flow, reduces cardiac contractility, slows heart rate, and slows electrical signal propagation in the heart.