Graft survival is improved by hepatic denervation before organ harvesting.
BACKGROUND
In a recent study, disturbances of hepatic microcirculation at harvesting caused by in situ organ manipulation dramatically reduced survival after a liver transplant. Because hepatic innervation is involved in the regulation of liver hemodynamics, the effect of denervation before harvesting was assessed here.


METHODS
The livers were harvested from female Lewis rats (200-230 g) within 25 min. Briefly, after minimal dissection during the first 12 min, the livers were either manipulated gently or left alone for 13 min. Subsequently, an orthotopic liver transplant was performed after 1 hr of storage in cold UW solution. Some donors livers underwent microsurgical denervation before harvesting or rats were given hexamethonium (10 mg/kg, i.v.), a ganglionic blocking agent.


RESULTS
In the nonmanipulated group, survival was 100% after the transplant; however, gentle manipulation decreased survival by about 50%. Furthermore, manipulation elevated serum transaminases and bilirubin 6- to 8-fold 8 hr after the transplant and caused necrosis of about 25% of hepatocytes. After organ harvesting, the rate of entry and exit of fluorescein dextran, a dye confined to the vascular space, was decreased 2- to 4-fold, and the maximal increase of surface fluorescence was blunted about 2-fold. Pimonidazole binding, which reflects tissue hypoxia, was increased 2-fold by manipulation. Denervation of the liver before organ harvesting or treatment with hexamethonium prevented the effects of organ manipulation on all parameters studied.


CONCLUSIONS
These data indicate for the first time that hepatic denervation before organ harvesting prevents detrimental effects of brief, gentle manipulation of the liver during harvesting on survival after the transplant. This is consistent with the hypothesis that organ manipulation disturbs the hepatic microcirculation and causes hypoxia at harvesting using mechanisms dependent on innervation.
Schemmer
P
P
Department of Pharmacology, University of North Carolina at Chapel Hill, 27599-7365, USA.
Bunzendahl
H
H
Raleigh
J A
JA
Thurman
R G
RG
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D003714:Denervation; D005260:Female; D006085:Graft Survival; D006499:Hepatic Artery / Q000294:innervation*; D018738:Hexamethonium / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology / Q000517:prevention & control; D008099:Liver / Q000098:blood supply*; D016031:Liver Transplantation / Q000276:immunology*; D008833:Microcirculation; D009593:Nitroimidazoles / Q000378:metabolism; D011838:Radiation-Sensitizing Agents / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000209:etiology; D009927:Tissue and Organ Procurement
D000959:Antihypertensive Agents; D009593:Nitroimidazoles; D011838:Radiation-Sensitizing Agents; D018738:Hexamethonium; C033815:pimonidazole