81

DIFFERENT LEVELS OF HYPOTHERMIA AND FUNCTION AND MORPHOLOGY OF THE RAT LIVER; BILE PRODUCTION AS A PARAMETER FOR LIVER FUNCTION.

G.N. de Ruijter, H.J. Houthoff**, R.A.F. Krom, P.A. Klok***, C.H. Gips*. Depts. of Surgery, *Medicine and **Pathology, University Hospital, and ***Central Animal Laboratory, University of Groningen, The Netherlands.

To study the function and morphology of the liver in hypothermia, and to assess the value of bile production a a parameter of liver function, 64 rat livers, half of which pretreated by one hour normothermic nonflow anoxia, were perfused with Eagle's medium for three hours in normothermia (37°C) and cooled (30, 20, IO°C). To determine whether cooling depresses bile production only or causes more severe damage, the livers were rewarmed and perfused normother- mieally during a fourth hour. Oxygenation, acid base balance and temperature were monitored frequently. PO~ was kept high (70 kPa at 37°C) and the perfusion pressure was fixed (.13 kPa). Taurocholate was infused continuously (.025 ~M/min). Bile production was measured every 30 minutes. P~ and PC02 , from which oxygenconsumption and respiratory quotient (RQ) were calcu- lated, were measured every hour. At the end of the experiments the livers were processed for light microscopy. In the unpretreated livers, bile production, V02and RQ were lower in the 20 and i0 ° groups than in the 37 and 30 ° groups (Wilcoxon: P .002, P .001 and P .001 resp.). There were no differences between 37 and 30 ° groups, nor between the 20 and i0 ° groups. After rewarming all differences disappeared. The livers of the 30, 20 and iO ° groups showed minor morphological changes, whereas the livers of the normothermic group showed steatosis and necrosis. In the livers, treated by normothermic nonflow anoxia, bile production was lower in all experiments at all temperatures (P .05). Oxygenconsumption and RQ showed no differences. All anoxic treated livers showed mild to marked steatosis and necrosis. Conclusions: l.Drastic alterations in metabolism and synthetic activity occur between 20 and 30°C. 2.Bile production is a good parameter for liver function at all temperatures studied. 3.37°C is not a tempera- ture that guarantees good preservation of structure of livers, perfused with Eagle's medium.

82

INFLUENCE OF FLUNARIZINE ON ANOXIC COMPROMIZED LIVERS: PRELIMINARY RESULTS.

G.N. de Ruijter, R.A.F. Krom, P. Metternich. Department of Surgery, University Hospital, Groningen, The Netherlands.

The cell protective effect of the calcium overload blocker flunarizine (Janssen Farmaca, Belgium) was studied in rat. Thirty two rat livers, half of which treated with flunarizine (flu) during flushing (500 ~g per liver), were subjected to one hour normothermic nonflow anoxia immediately before they were single pass perfused with Eagle's medium at 30 or I0 ° C during three hours, followed by one hour perfusion in normothermia (37°C). During perfusion oxygenation, acid base balance, temperature and perfusion pressure were monitored frequently and adjusted if necessary. Taurocholate was infused continuously. Determinations comprized metabolic parameters (oxygen consumption; carbondioxide production; respriatory quotient, RQ), perfusion characteristics (perfusate's flow, QP; vascular resistance), a synthetic parameter (bile production) and parameters for parenchymal integrity (SGOT; SGPT; dry/wet ratio). At I0 ° C flu treated livers had a lower vascular resistance during the first three hours of perfusion (Wilcoxon: P W~.OI), whereas the flu treated livers of the 30 ° group showed only a lower vascular resistance after rewarming (P <.05). SGPT and SGOT release war higher in all flu treated livers (P<.02). Furthermore, flu treated livers perfused at 30 ° C had a depres- sion of bile production, starting after two hours, lasting also after rewarming (P<.05). The other parameters showed no differences. Conclusions: i. Flunarizine exerts contradictory effects on isolated rat livers, subjected to normo~hermic nonflow anoxia, lower vascular resistance, depression of bile production, higher SGPT and SGOT release. 2. Therefore, in this model the cell protective effect of flunarizine on anoxic compromized livers remains inconclusive.

S219