Plastics have revolutionized medical device technology, transformed hematological care, and facilitated modern cardiology procedures. Despite these advances, studies have shown that phthalate chemicals migrate out of plastic products and that these chemicals are bioactive. Recent epidemiological and research studies have suggested that phthalate exposure adversely affects cardiovascular function. Our objective was to assess the safety and biocompatibility of phthalate chemicals and resolve the impact on cardiovascular and autonomic physiology. Adult mice were implanted with radiofrequency transmitters to monitor heart rate variability, blood pressure, and autonomic regulation in response to di-2-ethylhexyl-phthalate (DEHP) exposure. DEHP-treated animals displayed a decrease in heart rate variability (-17% SD of normal beat-to-beat intervals and -36% high-frequency power) and an exaggerated mean arterial pressure response to ganglionic blockade (31.5% via chlorisondamine). In response to a conditioned stressor, DEHP-treated animals displayed enhanced cardiovascular reactivity (-56% SD major axis Poincarè plot) and prolonged blood pressure recovery. Alterations in cardiac gene expression of endothelin-1, angiotensin-converting enzyme, and nitric oxide synthase may partly explain these cardiovascular alterations. This is the first study to show an association between phthalate chemicals that are used in medical devices with alterations in autonomic regulation, heart rate variability, and cardiovascular reactivity. Because changes in autonomic balance often precede clinical manifestations of hypertension, atherosclerosis, and conduction abnormalities, future studies are warranted to assess the downstream impact of plastic chemical exposure on end-organ function in sensitive patient populations. This study also highlights the importance of adopting safer biomaterials, chemicals, and/or surface coatings for use in medical devices. Phthalates are widely used in the manufacturing of consumer and medical products. In the present study, di-2-ethylhexyl-phthalate exposure was associated with alterations in heart rate variability and cardiovascular reactivity. This highlights the importance of investigating the impact of phthalates on health and identifying suitable alternatives for medical device manufacturing.

Bisphenol chemicals are commonly used in the manufacturing of polycarbonate plastics, polyvinyl chloride plastics, resins, and thermal printing applications. Humans are inadvertently exposed to bisphenols through contact with consumer products and/or medical devices. Recent reports have shown a link between bisphenol-a (BPA) exposure and adverse cardiovascular outcomes; although these studies have been limited to adult subjects and models. Since cardiac physiology differs significantly between the developing and adult heart, we aimed to assess the impact of BPA exposure on cardiac function, using a neonatal cardiomyocyte model. Neonatal rat ventricular myocytes were monitored to assess cell viability, spontaneous beating rate, beat rate variability, and calcium-handling parameters in the presence of control or bisphenol-supplemented media. A range of doses were tested to mimic environmental exposure (10−9–10−8M), maximum clinical exposure (10−5M), and supraphysiological exposure levels (10−4M). Acute BPA exposure altered cardiomyocyte functionality, resulting in a slowed spontaneous beating rate and increased beat rate variability. BPA exposure also impaired intracellular calcium handling, resulting in diminished calcium transient amplitudes, prolonged calcium transient upstroke and duration time. Alterations in calcium handling also increased the propensity for alternans and skipped beats. Notably, the effect of BPA-treatment on calcium handling was partially reversible. Our data suggest that acute BPA exposure could precipitate secondary adverse effects on contractile performance and/or electrical alternans, both of which are dependent on intracellular calcium homeostasis.

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Di-2-ethylhexyl phthalate (DEHP) is a plasticizer that is used to impart flexibility to polyvinyl chloride products. Patients have an increased exposure to phthalates through contact with DEHP-containing medical devices, including: storage bags containing blood, plasma, intravenous fluids, total parenteral nutrition, tubing associated with their administration, nasogastric tubes, enteral feeding tubes, catheters, extracorporeal membrane oxygenation (ECMO) circuits, hemodialysis tubing, respiratory masks and endotracheal tubes. Human health concerns pertaining to DEHP exposure are linked to its endocrine-disrupting properties. Accordingly, increased exposure has been associated with cancer, metabolic disturbances, reproductive and neurological disorders, and cardiovascular disease. As an example, epidemiological studies have shown a link between DEHP exposure and elevated systolic blood pressure in adolescents. Despite bans and restrictions on the use of DEHP-containing medical devices in other countries, there is currently no mandate from the Food & Drug Administration for the use of DEHP-free devices and storage containers. The objective of this study was to quantify the impact of in vivo DEHP exposure on cardiovascular function; thereby, providing additional information for regulatory decisions by the scientific, medical and regulatory community. Healthy C57BL/6 male mice were implanted with radiotelemetry transmitters; briefly, the transmitter catheter was placed in the carotid artery and biopotential leads were routed subcutaneously to collect electrocardiogram (ECG) signals. After surgical recovery, pre-exposure data was collected, and thereafter, animals were exposed to 0.2 mg/g DEHP or control diet. We observed a significant increase in systolic pressure in DEHP-treated (145 + 3 mmHg) vs control animals (136 + 1 mmHg). We also detected an increase in diastolic and mean arterial pressure in DEHP-treated (119 + 5 and 132 + 3 mmHg, respectively) vs control animals (107 + 2 and 121 + 2 mmHg). Our previous reports have shown that DEHP diminishes cardiac contractility, which suggests that these effects on blood pressure are likely attributed to alterations in sympathetic tone and/or an increase in vascular resistance.