Large Intravenous Loads of Bilirubin Photoconversion Products, in Contrast to Bilirubin, Do Not Cause Cholestasis in Bile Acid-Depleted Pigs
Bjørn Atle Bjørnbeth, Olaug Villanger, Terje Christensen, Torstein Lyberg, Morten G. Ræder
Abstract
Bjørn Atle Bjørnbeth, Olaug Villanger, Terje Christensen, Torstein Lyberg, Morten G. Ræder
Abstract
BACKGROUND: Large intravenous bilirubin infusions in bile acid-depleted pigs (BADP) destroy hepatocyte canalicular membrane microvilli (CMV) and cause cholestasis. This study examines whether bilirubin photoconversion product infusions do the same. METHODS: The effects of systemic infusion of 135 mumol.kg-1 body weight bilirubin photoconversion products on CMV density and choleretic response to intraportal bile acid infusion were studied in BADP. Furthermore, the effects of 135 mumol.kg-1 b.w. bilirubin infusion, either through an arteriovenous bilirubin photoconversion shunt device (PCD) or intravenously, were measured in PCD-connected BADP. RESULTS: Intravenous bilirubin photoconversion product infusions affected neither the CMV density nor the choleretic response to cholic acid infusion, and neither did bilirubin infusion through the PCD. In contrast, intravenous bilirubin infusion caused canalicular injury and cholestasis in four of six PCD-connected BADP. CONCLUSION: Bilirubin photoconversion products do not destroy CMV or cause cholestasis in BADP. A bilirubin photoconversion shunt device can confer cholestasis protection to bilirubin-loaded BADP.
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BACKGROUND: Large intravenous bilirubin infusions in bile acid-depleted pigs (BADP) destroy hepatocyte canalicular membrane microvilli (CMV) and cause cholestasis. This study examines whether bilirubin photoconversion product infusions do the same. METHODS: The effects of systemic infusion of 135 mumol.kg-1 body weight bilirubin photoconversion products on CMV density and choleretic response to intraportal bile acid infusion were studied in BADP. Furthermore, the effects of 135 mumol.kg-1 b.w. bilirubin infusion, either through an arteriovenous bilirubin photoconversion shunt device (PCD) or intravenously, were measured in PCD-connected BADP. RESULTS: Intravenous bilirubin photoconversion product infusions affected neither the CMV density nor the choleretic response to cholic acid infusion, and neither did bilirubin infusion through the PCD. In contrast, intravenous bilirubin infusion caused canalicular injury and cholestasis in four of six PCD-connected BADP. CONCLUSION: Bilirubin photoconversion products do not destroy CMV or cause cholestasis in BADP. A bilirubin photoconversion shunt device can confer cholestasis protection to bilirubin-loaded BADP.
Key concepts: Cholestasis, Bilirubin, Bile acid, Medicine, Gastroenterology, Internal medicine, Chemistry