Nearly 15 million transfusions are performed in the United States each year, with approximately 425,000 units transfused to pediatric patients alone. Despite the frequency ? transfusion procedures are not without risk. Blood transfusion complications may be attributed to heavy exposure to plastic devices, which are fabricated with chemicals that exert endocrine disrupting properties. The proposal's main hypothesis is that plastic devices are not universally biocompatible ? and that local and systemic reactions to chemical contaminants contribute to transfusion-related complications. The proposal's objective is to assess whether medical device biocompatibility and chemical exposures are underlying contributors to cardiovascular and autonomic dysfunction. The proposal also aims to identify safer biomaterials, chemicals and/or surface coatings for transfusion devices and blood banking. In this proposal, we will build upon our preliminary studies to address three specific aims: 1) To define the extent to which biomaterial leaching and chemical exposure alters cardiovascular and autonomic function, using in vivo and whole heart models. 2) To determine if biocompatibility and incidental chemical exposures are correlated with cardiovascular and autonomic abnormalities in transfused pediatric patients. 3) To compare and contrast alternative biomaterials, chemicals and fabrication techniques in order to identify safer replacements for transfusion-related devices. The proposed application will quantify the role of biocompatibility and chemical leaching on cardiovascular and autonomic function ? two targets that are highly susceptible to xenobiotic toxicity. If adverse outcomes are observed in the proposed study, it will pinpoint additional variables to monitor in future clinical investigations and epidemiological studies. Finally, this proposal aims to provide the foundation for objective decision making regarding the use of chemical additives with endocrine disrupting properties in medical device manufacturing by scientific, medical and regulatory communities. Results of the proposed studies can incentivize and accelerate the development and clinical adoption of alternative biomaterials, additives and/or fabrication techniques to improve transfusion patient safety.

Public Health Relevance

Blood transfusion complications may be attributed to heavy exposure to plastic devices, which are fabricated with chemicals that exert endocrine-disrupting effects. The proposal's objective is to investigate the safety and biocompatibility of transfusion devices and the impact of incidental chemical exposures on vulnerable patient populations. The proposal also aims to identify safer biomaterials, chemicals and/or surface coatings for transfusion devices and blood banking.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL139472-02
Application #
9624455
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mondoro, Traci
Project Start
2018-01-15
Project End
2022-12-31
Budget Start
2019-01-01
Budget End
2019-12-31
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Children's Research Institute
Department
Type
DUNS #
143983562
City
Washington
State
DC
Country
United States
Zip Code
20010
Tereshchenko, Larisa G; Posnack, Nikki G (2018) Does plastic chemical exposure contribute to sudden death of patients on dialysis? Heart Rhythm :
Ramadan, Manelle; Sherman, Meredith; Jaimes 3rd, Rafael et al. (2018) Disruption of neonatal cardiomyocyte physiology following exposure to bisphenol-a. Sci Rep 8:7356