title: Hepatic insufficiency after portacaval shunting is prevented by prior intraportal pancreatic islet autotransplantation.
abstract: The extrahepatic diversion of essential splanchnic hepatotrophic factors may cause the liver atrophy and insufficiency that follows portacaval shunting. To investigate this, control dogs with end-to-side portacaval shunts (control-PCS, n = 6) were compared with dogs shunted 1 month after intraportal pancreatic islet autotransplantation (islet-Tx-PCS, n = 5). From the distal pancreas of each experimental dog, 1.95 +/- 0.49 X 10(5) islets were isolated by collagenase digestion and retransplanted within 3 hours. Assays of hepatocellular function (caffeine clearance) and hepatic blood flow (indocyanine green), conventional biochemical liver function tests, and glucose, insulin, and glucagon responses to intravenous glucose challenge were measured monthly and when dogs were killed. Four of six control-PCS dogs were killed 32 +/- 9 days after shunting because of more than 20% body weight loss; one control-PCS dog lost only 7% of body weight by day 56 and stabilized. No significant loss of body weight occurred in islet-Tx-PCS dogs (n = 5). Liver function test abnormalities seen in control-PCS dogs were absent in islet-Tx-PCS dogs. Both control-PCS and islet-Tx-PCS indocyanine green half-life measurements were significantly (p less than 0.05) prolonged at all times, indicating equally reduced hepatic blood flow after shunting for both groups. In contrast, islet-Tx-PCS caffeine half-life periods were significantly (p less than 0.05) shorter than in control-PCS dogs and were similar to those in normal dogs, indicating a protective effect of the transplanted islets on hepatocellular function. We conclude that intraportal pancreatic islet autotransplants prevent, by the local release of hepatotrophic factors within the liver, the metabolic abnormalities and loss of hepatic function after PCS.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110.
authors.forename: M P
authors.initials: MP
authors.lastname: Callery
authors.forename: C
authors.initials: C
authors.lastname: Ricordi
authors.forename: D W
authors.initials: DW
authors.lastname: Scharp
authors.forename: T
authors.initials: T
authors.lastname: Kamei
authors.forename: C J
authors.initials: CJ
authors.lastname: Swanson
authors.forename: P E
authors.initials: PE
authors.lastname: Lacy
authors.forename: M W
authors.initials: MW
authors.lastname: Flye
mesh_terms: D000818:Animals; D002110:Caffeine / Q000378:metabolism; D004285:Dogs; D005260:Female; D005951:Glucose Tolerance Test; D007208:Indocyanine Green; D016381:Islets of Langerhans Transplantation; D008099:Liver / Q000378:metabolism; D008102:Liver Circulation; D008107:Liver Diseases / Q000209:etiology / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D011167:Portacaval Shunt, Surgical / Q000009:adverse effects*; D011168:Portal System / Q000502:physiology*; D014182:Transplantation, Autologous
chemical_list: D002110:Caffeine; D007208:Indocyanine Green