Abstract 581: Protective Effects Of Bilirubin Administration On Placental Ischemia-induced Hypertension
Preeclampsia is one of the most common complications of pregnancy in humans, and is a leading cause of premature birth and fetal perinatal morbidity and mortality. The hallmark of the disorder is the manifestation of new-onset hypertension-typically after the 20th week of gestation. While the underlying cause of the disorder remains obscure, it is widely held that failure of the maternal vasculature to adequately remodel and supply the developing placenta with adequate blood flow leads to placental insufficiency and resulting ischemia. In response placental derived factors, namely the anti-angiogenic protein sFlt-1 and reactive oxygen species- are released into the maternal circulation resulting in the symptomatic phase of the. We have recently demonstrated that induction of heme oxygenase in a rodent model of placental ischemia attenuates the associated hypertension by blocking both of these pathways, presumably through byproducts carbon monoxide and bilirubin. Here, we have investigated the in vivo effects of exogenous bilirubin administration on a rodent model of placental ischemia-induced hypertension, the reduced uterine perfusion pressure (RUPP) model. RUPP animals exhibited significant increases in MAP when compared to sham animals (109 ± 3 vs 120 ± 4 mmHg, p<0.05). Exogenous administration of bilirubin (30mg/kg/q 48h, i.p.) had no significant effect on MAP in sham animals (101 ± 2 mmHg), but significantly decreased MAP in RUPP animals (107 ± 2 mmHg, p<0.05), returning pressure to sham control levels. Promisingly, bilirubin administration had no detrimental effect on fetal weight (2.5 ± 0.14 vs 2.2 ± .28 g) or incidence of fetal loss (6 ±2% shams vs 3 ± 2% treated). In RUPP animals, which have significantly increased incidence of fetal loss compared to controls (69 ± 6%, p<0.005), bilirubin tended to decrease fetal loss (43 ± 13%), however, this did not meet statistical significance. In summary, bilirubin administration attenuated the hypertension associated with placental ischemia, and moderately increased bilirubin is a potential mechanism to explain the therapeutic effects of heme oxygenase induction in this clinically relevant model for the study of preeclampsia.
Author Disclosures: E.M. George: None. D.E. Stec: None. J.P. Granger: None.
- © 2014 by American Heart Association, Inc.