February 24th, 2021

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Effect of Taurocholic Acid on Fetoplacental Arterial Pressures in a Dual Perfusion Placental Cotyledon Model: A Novel Approach to Intrahepatic Cholestasis of Pregnancy
Authors:  Brad M. Dolinsky, M.D., Craig M. Zelig, M.D., Damian J. Paonessa, M.D., Nathan J. Hoeldtke, M.D., and Peter G. Napolitano, M.D.
  OBJECTIVE: To determine if continuous infusion of taurocholic acid into the fetoplacental and intervillous circulation of a placental cotyledon affects the fetal arterial pressure response after injection of the thromboxane mimetic U44619. Taurine conjugated bile acid is one bile acid putatively mediating intrahepatic cholestasis of pregnancy (ICP).

STUDY DESIGN: We selected 5 placentas from normal, unlabored patients. Two cotyledons from each placenta were isolated and dually perfused. Taurocholic acid was continuously infused into the fetoplacental and intervillous circulation of the test cotyledon. After 30 minutes U44619 was injected into both the test and control cotyledon vascular circuits. Pressure excursions were measured and compared to baseline pressures using a paired Studentís t test.

RESULTS: There was significant attenuation of the pressure excursion in the cotyledons perfused with taurocholic acid as compared to controls after injection of U44619. The difference from baseline in the taurocholic cotyledon compared with controls was 44.2 mmHg vs. 71.8 mmHg (p=0.009).

CONCLUSION: The perfusion of taurocholic acid attenuated the pressure response to thromboxane mimetic U44619 in the fetoplacental arterial circulation of a placental cotyledon as compared to control. This finding in our ex-vivo model may represent changes that occur in the placental vasculature with intrahepatic cholestasis of pregnancy. These placentas may have dysregulated vascular tone, which could contribute to the adverse fetal effects observed in ICP.
Keywords:  bile acid, intrahepatic cholestasis, intrahepatic cholestasis of pregnancy, liver, pregnancy complications, taurocholic acid, thromboxane mimetic U44619
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