EFFECT OF FASTING ON HEPATOCYTES COLD-STORED IN UNIVERSITY-OF-WISCONSIN SOLUTION FOR 24 HOURS

Although there have been improvements in liver preservation, liver dys function still remains a serious consequence of liver transplantation. This may be related to cold ischemic injury since the incidence of dy sfunction increases with longer preservation times. However, even some livers preserved for short periods of time (less than 15 hr) develop liver dysfunction. One possible cause may be the lack of adequate nutr itional support, and the donor may be exposed to prolonged periods of hyponutrition. In this study, we have compared the effects of fasting on functions of hepatocytes isolated from the rat. Hepatocytes were co ld stored in University of Wisconsin solution for 24 hr and analyzed a t the end of preservation as well as at the end of rewarming in Krebs- Henseleit buffer for 120 min. The glycogen content of fed cells was 1. 57 mu mol/mg protein and this was reduced by 95% in cells from fasted rats. After cold storage and rewarming, hepatocytes from fasted rats l ost 84.2+/-2.5% of the total cellular lactate dehydrogenase versus onl y 32.7+/-3.8% (P<0.001) in cells from fed rats. Also, ATP and reduced glutathione content of fasted cells were significantly reduced, free f atty acids were higher (P=0.0154), and protein synthesis was reduced t o 41% of controls (versus only 88% in fed cells), although there were no differences in phospholipid content. When hepatocytes from fasted r ats were rewarmed in Krebs-Henseleit buffer containing fructose (10 mM ), lactate dehydrogenase release was reduced from 80% to 34.4+/-0.2% a nd ATP content was significantly higher with fructose than without. He patocytes from fasted rats, therefore, are more sensitive to cold isch emic injury than cells from fed rats. The increased sensitivity appear s related to the lack of glycogen as a source of substrates for metabo lism during rewarming. This is supported by the fact that addition of fructose, which is metabolized readily by hepatocytes through glycolys is, suppressed rewarming injury to cells from fasted rats. The nutriti onal status of the donor, therefore, may play a pivotal role in the re sults of liver preservation and transplantation. Effective donor nutri tional management may reduce the incidence of liver dysfunction after transplantation.