The effect of mono(2-ethylhexyl)phthalate on an isolated perfused rat heart-lung preparation.
Di(2-ethylhexyl)phthalate (DEHP), the plasticizer used in the biomedical production of blood storage bags, hemodialysis systems, cardiopulmonary bypass (CPB) circuitry, and intubation tubes, is extracted from the plastic material when it comes into contact with biological fluids and is converted to its principal metabolite, mono(2-ethylhexyl)phthalate (MEHP). We have shown that MEHP causes cardiac and respiratory arrest, as well as hypotension, when infused into anesthetized rats. Using a well-ventilated in vitro rat heart-lung preparation, we investigated the effect of MEHP on pulmonary artery pressure (PAP) and found that MEHP had a hypertensive effect on the pulmonary vasculature ending in constriction and edema. There was a significant increase of 0.58 mm Hg/min in the PAP of isolated rat lungs when perfused with MEHP dissolved in Krebs-Henseleit (K-H) buffer (p = 0.0003). The rat lungs that were perfused with K-H buffer only increased 0.094 mm Hg/min during the same perfusion time of 20 min. The water gained during this time was 0.22 g/min with MEHP in the buffer compared to 0.04 g/min with buffer alone. The pO2 in the effluent did not decrease during the perfusion time. The concentration of MEHP in the rat lungs after perfusion varied from 20 to 40 micrograms/g. Although the mechanism of action of MEHP on PAP is too complex to be fully elucidated by this model, the increase in PAP which we have demonstrated is significant and adds yet another toxic effect of this major metabolite of the ubiquitous plasticizer, DEHP.
Labow
R S
RS
University of Ottawa Heart Institute, Ottawa Civic Hospital, Ontario, Canada.
Barry
Y A
YA
Tocchi
M
M
Keon
W J
WJ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001834:Body Water / Q000187:drug effects / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000633:toxicity* / Q000031:analogs & derivatives; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D010477:Perfusion; D010968:Plasticizers / Q000633:toxicity; D011651:Pulmonary Artery / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D010968:Plasticizers; D004051:Diethylhexyl Phthalate; C016599:mono-(2-ethylhexyl)phthalate