LIVER-TRANSPLANTATION IS ASSOCIATED WITH INCREASED MET-ENKEPHALIN LEVELS IN THE PIG

Background: It has been reported that less postoperative morphine is r equired following liver transplantation than is required following ope n cholecystectomy. This may be attributable to endogenous factors rath er than to altered morphine pharmacokinetics. We measured the plasma c oncentrations of two endogenous neuropeptides associated with pain mod ulation, substance P(SP) and met-enkephalin (ME), in pigs undergoing l iver transplantation and in control pigs undergoing laparotomy. Method s: With the approval of the institutional Animal Care Committee, pigs were anaesthetized with ketamine (30 mg/kg,IM), atropine (0.05 mg/kg,I M) and acetylpromazine (0.1 mg/kg,IM). Anesthesia was maintained with isoflurane in oxygen. Pigs in the transplantation group (n=10) underwe nt liver transplantation and control pigs (n=10) underwent laparotomy. Blood samples for SP and ME measurement were collected pre-incision ( Pre-In), pre-emergence (Pre-Em) from anesthesia, 6-12 hours, 18 hours, and 24 hours after surgery. SP and ME levels were determined by radio immunoassay. Results are expressed as mean+/-SEM (in pg/ml of plasma f or both peptides) and were compared by the non-parametric Mann-Whitney U test. Statistical significance was inferred if P<0.05. Results: Pla sma ME levels were significantly increased in the transplanted pigs at Pre-Em, 6-12 hours and 18 hours after surgery. No statistically signi ficant difference was observed for plasma SP level between the control and transplant pigs. Conclusions: Liver transplantation in the pig mo del is associated with increased concentrations of endogenous ME (but not SP) in plasma for at least 18 hours after surgery as compared to a nimals undergoing laparotomy.