School of Medicine and Health Sciences Poster Presentations

Title

Exposure to Di-2-Ethylhexylphthalate Affects Blood Pressure and Electrocardiograms in Mice.

Poster Number

116

Document Type

Poster

Publication Date

3-2016

Abstract

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is used in the manufacturing of FDA approved medical devices and consumer products that employ polyvinyl chloride (PVC) (1). DEHP can comprise up to 40% of the total weight of intravenous bags, and up to 80% of medical tubing. DEHP concentrations can reach 200-300 μg/mL in blood storage bags. Previous studies have identified a link between DEHP exposure and alterations in cardiomyocyte function in vitro; this study aimed to determine the adverse effects of DEHP in an in vivo model using a clinically relevant exposure.

Radiotelemetry transmitters (DSI) were surgically implanted into male C57/BL/6 mice (n=8) to record blood pressure and electrocardiograms in freely moving animals. Briefly, the transmitter catheter was placed in the carotid artery to measure blood pressure and biopotential leads were routed subcutaneously to collect an ECG signal. After post-surgical recovery, animals were placed on a control diet or exposed to 200 mg/kg/day DEHP for 4-8 weeks via drinking water. Blood pressure and ECG signals were collected continuously via receivers positioned underneath the animal cages. Data was collected via DSI Dataquest A.R.T., and ECG parameters were analyzed via Ponemah software. Data analysis was performed using Graphpad (Student’s t-test) with significance determined at p<0.05.

No significant changes were noted in animal weight, heart weight, water consumption or behavior. A significant increase in systolic blood pressure was observed in the DEHP-treated animals (145± 3 mmHg) compared to the control animals (136 ± 1 mmHg). In the DEHP-treated animals there were notable increases in diastolic pressure (119 ± 5 mmHg) and mean arterial pressure (132 ± 3 mmHg). The control animals had diastolic and mean arterial pressures of 107 ± 2 and 121 ± 2mmHg respectively. We also observed significant slowing in electrical conduction between the atria and ventricle, as determined by ECG PR interval time, in DEHP-treated animals. PR interval time was 42.6 ± 0.4 ms in DEHP-treated animals versus 39.3 ± 1.1 ms in controls. However, no significant changes to QRS complex were observed. Previous reports have demonstrated that DEHP has a diminishing affect on cardiac contractility, suggesting these changes in blood pressure are possibly caused by alterations in sympathetic tone and/or increased vascular resistance. Results of comprehensive in vivo studies are necessary to guide the regulation and utilization of DEHP in medical devices.

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Open Access

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Presented at: GW Research Days 2016

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Exposure to Di-2-Ethylhexylphthalate Affects Blood Pressure and Electrocardiograms in Mice.

Di(2-ethylhexyl) phthalate (DEHP) is a plasticizer that is used in the manufacturing of FDA approved medical devices and consumer products that employ polyvinyl chloride (PVC) (1). DEHP can comprise up to 40% of the total weight of intravenous bags, and up to 80% of medical tubing. DEHP concentrations can reach 200-300 μg/mL in blood storage bags. Previous studies have identified a link between DEHP exposure and alterations in cardiomyocyte function in vitro; this study aimed to determine the adverse effects of DEHP in an in vivo model using a clinically relevant exposure.

Radiotelemetry transmitters (DSI) were surgically implanted into male C57/BL/6 mice (n=8) to record blood pressure and electrocardiograms in freely moving animals. Briefly, the transmitter catheter was placed in the carotid artery to measure blood pressure and biopotential leads were routed subcutaneously to collect an ECG signal. After post-surgical recovery, animals were placed on a control diet or exposed to 200 mg/kg/day DEHP for 4-8 weeks via drinking water. Blood pressure and ECG signals were collected continuously via receivers positioned underneath the animal cages. Data was collected via DSI Dataquest A.R.T., and ECG parameters were analyzed via Ponemah software. Data analysis was performed using Graphpad (Student’s t-test) with significance determined at p<0.05.

No significant changes were noted in animal weight, heart weight, water consumption or behavior. A significant increase in systolic blood pressure was observed in the DEHP-treated animals (145± 3 mmHg) compared to the control animals (136 ± 1 mmHg). In the DEHP-treated animals there were notable increases in diastolic pressure (119 ± 5 mmHg) and mean arterial pressure (132 ± 3 mmHg). The control animals had diastolic and mean arterial pressures of 107 ± 2 and 121 ± 2mmHg respectively. We also observed significant slowing in electrical conduction between the atria and ventricle, as determined by ECG PR interval time, in DEHP-treated animals. PR interval time was 42.6 ± 0.4 ms in DEHP-treated animals versus 39.3 ± 1.1 ms in controls. However, no significant changes to QRS complex were observed. Previous reports have demonstrated that DEHP has a diminishing affect on cardiac contractility, suggesting these changes in blood pressure are possibly caused by alterations in sympathetic tone and/or increased vascular resistance. Results of comprehensive in vivo studies are necessary to guide the regulation and utilization of DEHP in medical devices.