title: Intraportal hepatocyte transplantation in the pig: hemodynamic and histopathological study.
abstract: BACKGROUND
  Hepatocyte transplantation is an attractive treatment for various liver diseases. The intraportal route of transplantation is favored, but little information is available on the possible adverse effects in this technique. We investigated the influence of intraportal loads of hepatocytes on portal, pulmonary, and systemic hemodynamics in 13 pigs.
  
  
  METHODS
  Under general anesthesia, pigs were provided with an arterial line, a Swan-Ganz catheter, and two intraportal catheters, one for cell infusion and one for heparin infusion and portal pressure measurement. Pig hepatocytes were infused at a rate of 25 million cells/min.
  
  
  RESULTS
  The first six animals were used to develop the infusion technique. In the last seven animals, portal pressure increased linearly with cell load upon infusion of 400-2400 x 10(6) hepatocytes (r(2)=0.704;P<0.05). Portal flow measured by Doppler sonography decreased by 23-66% below basal values. An inverse linear relationship was found between portal pressure and portal flow (r(2)=0.679; P<0.05), portal flow approaching zero for portal pressure >40 mmHg. Pulmonary arterial pressure increased by 11-62%. AST increased up to 10-fold, and platelets decreased by 22-58%. Hepatocytes-containing thrombi were present in segmental and in smaller portal branches. Hepatocytes were always identified in lung sinusoids 48 hr after infusion, and a small basal pulmonary infarction was found in one animal.
  
  
  CONCLUSIONS
  . These data suggest that up to 2.4% of total hepatocyte mass can be infused in this large animal model. However, the risk of significant thrombotic complications should be considered for clinical applications.
authors.affiliation: Department of Medical and Surgical Sciences, University of Padova, Italy. muraca@ux1.unipd.it
authors.forename: Maurizio
authors.initials: M
authors.lastname: Muraca
authors.forename: Danielle
authors.initials: D
authors.lastname: Neri
authors.forename: Anna
authors.initials: A
authors.lastname: Parenti
authors.forename: Paolo
authors.initials: P
authors.lastname: Feltracco
authors.forename: Anna
authors.initials: A
authors.lastname: Granato
authors.forename: Maria Therese
authors.initials: MT
authors.lastname: Vilei
authors.forename: Chiara
authors.initials: C
authors.lastname: Ferraresso
authors.forename: Roberto
authors.initials: R
authors.lastname: Ballarin
authors.forename: Gian Eros
authors.initials: GE
authors.lastname: Zanusso
authors.forename: Gianpiero
authors.initials: G
authors.lastname: Giron
authors.forename: Jacek
authors.initials: J
authors.lastname: Rozga
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gerunda
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D017690:Cell Transplantation / Q000379:methods; D006400:Hematocrit; D006439:Hemodynamics / Q000502:physiology*; D022781:Hepatocytes / Q000637:transplantation*; D007958:Leukocyte Count; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation / Q000473:pathology / Q000502:physiology; D008168:Lung / Q000473:pathology; D011168:Portal System; D013552:Swine; D014184:Transplantation, Homologous / Q000473:pathology / Q000502:physiology*