p.61 OXIDATION OF FAT AND GLUCOSE DURING INFUSION OF HEPARIN AND LOW MOLECULAR WEIGHT HEPARIN E. Persson, J. Nordenstrom, J. Wahren, Dept of Anaesthesiology, Karolinska Hospital and Depts of Surgery and Clinical Physiology, Huddinge Univ. Hospital, Stockholm, Sweden

Heparin activates lipoprotein (LPL), which leads to an increased hydrolysis of trigly- ceride-rich particles and increased free fatty acid (FFA) concentration in plasma. Therefore, addition of heparin to fat emulsions has been recommended on the assumption that oxidation of fat in various organs would be augmented by increasing the availabi- lity of FFA. This study examines the effect of heparin and low molecular weight heparin (LMWH), respectively on energy substrate oxidation in healthy male subjects. Methods. Indirect calorimetry was performed continuously for 5 hours in 9 healthy male subjects. After 60 min of baseline measurements an infusion of Intralipid (0.2 g/min) and glucose (0.8 g/min) was given for 4 hours. At 120 min, a 1 hour infusion of either of heparin, LMWH (100 U/kg/h) or saline was added. Results. The metabolic rate (MR) increased linearly during the entire fat/glucose infu- -period. The mean respiratroy quotient (RQ) and MR increased by 4-8% and 18% respec- tively. The average increase in glucose oxidation was 40-55%, fat oxidation decreased by lo-30%. Neither infusion of heparin (n=3), LMWH (n=3) or saline (n=3) influenced RQ or MR. The decrease in Intralipid cont. was more pronounced with heparin (1.52-0.45 mmol/l) than with LMWH (1.15-1.05). The FFA cont. during fat/glucose infusion was 0.27kO.02 (SEM) mmol/l and increased to 1.35kO.36 with heparin and to 0.91tO.16 with LMWH. No changes were seen with saline. Plasma levels of glucose and insulin increased similarly in all three groups.

Conclusions. Infusion of heparin results in a pronounced increase in FFA availability, whereas LMWH exerts a less marked lipolytic effect. Fat oxidation did not rise in re- sponse to augmented FFA availability. When fat emulsion and glucose are given to healthy subjects, glucose seems to be the preferred oxidative substrate. The rationale for add- ing heparin to fat emulsions to promote fat oxidation is not apparent.

p.62 DRUG-NUTRIENT INTERACTIONS IN THE ISOLATED PERFUSED RAT LIVER (IPRL).

J. di Costanzo JF. Tizon, B. Richard, H. Lafont, J. di Costanzo-Dufetel, --------------' G. Fabre, JP. Cano. INSERM U 278, Faculte de Pharmacie, Marseilles, France.

1PRL is a valuable model for the investigation of nutrient and drug meta- bolism. The aim of this work was to assess the interactions between nutri- ent supply and drug biotransformation in the liver.

Livers were perfused via the portal vein in a single pass mode for 3 hours. 5 groups of 3 animals were studied. The perfusate was : in group 1 (Gl) Krebs-Henseleit buffer ; in group 2 (G2) nutritive mixture (NM) containing

amino acids (AA), fatty acid (FA), insuline, glucagon, serum albumin, tau- rocholate, glucose, vitamins and electrolytes ; in group 3 (G3) FA was withdrawn ; in group 4 (G4), hormones were removed ; in group 5 (G5) hor- mones and FA were suppressed. Diazepam (5 mg, 14C 1abelled)was simultane- ously infused for 50 mn. The amounts of radioactivity of unchanged Diaze- pam and of metabolites were determined by HPLC both in the outflow and in bile.

Comparison between Gl and other groups showed : 1/ in the outflow : a) higher overall metabolite production in Gl (1.81~0.27 pg/ml) than in G2 to G5 (1.5620.21 pg/ml) mainly due to high amounts of N.Methyl oxazepam (0.57~0.06 pg/ml) VS (0.19+0.03 pg/ml) (pcO.Olj. b j a conjugated metabo- lite only present in G2 to G5 (0.3O~O.06 &g/ml). 2/in bile : no difference in metabolite secretion. Comparison between groups G2 to G5 showed a/ no difference in metabolite production. b/ higher Diazepam extraction coeffi- cient in G5 (0.621~16) than in G2 to G4 (0.480~12).c / in bile more impor- tant amounts of Diazepam metabolites in G5 (4.6220.3 ug/ml) than in G2 to G4 (2.8~0.2 pg/ml) (~~0.05).

Presence of nutrients in the portal vein changes the hepatic drug biotrans- formation.AA,FA and hormones interact with drug uptake or elimination.

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