Influence of Glucose Infusion on Levels of Phosphomonoesters and Adenosine Triphosphate as Detected by Magnetic Resonance Spectroscopy in a New Model of Core-Cooling of the Rat Liver In Situ

Abstract

This preliminary study was undertaken to ascertain whether our newly developed model of the cold ischemic rat liver in situ is applicable to studies designed to assess the metabolism of nutrients. Ischemia of the whole liver of 12 Wistar rats was induced by clamping all supply and drainage vessels. The ischemic liver was perfused in situ. The duration of ischemia of the liver was 20 minutes. Saline was infused into six rats throughout the experiment (group A). An intravenous infusion of glucose at a rate of 0.75 g/h per rat was begun immediately after the induction of blood-reflow to the liver (group B, n = 6). Six rats (group C) did not undergo the procedure for induction of hepatic ischemia and received glucose at the same rate as rats in group B. Changes in hepatic levels of sugar phosphates (phosphomonoesters [PMEs]), inorganic phosphorus, and β-positioned phosphorus in adenosine triphosphate (β-ATP) were monitored by ³¹P magnetic resonance spectroscopy. Ischemia caused a significant increase in levels of PMEs and a decrease in levels of β-ATP. The infusion of glucose caused a further increase in levels of PMEs and a further decrease in levels of β-ATP in group B. In contrast, in group C such infusion did not induce any changes in levels of PMEs or β-ATP. In group A, PMEs and β-ATP returned to basal levels 5 hours after the induction of blood-reflow to the liver. The changes in levels of PMEs were similar to those in levels of inorganic phosphorus in all groups. All rats in groups A and C regained consciousness and survived, whereas all rats in group B died 4 or 5 hours after the induction of blood-reflow to the liver. Thus, it was demonstrated that the early supply of large amounts of glucose induces the accumulation of sugar phosphates and inhibits restoration of hepatic levels of ATP. The results suggest that our newly developed model of cold ischemia of the rat liver in situ can be applied to studies designed to elucidate appropriate nutrients for the liver recovering from cold ischemia. (Journal of Parenteral and Enteral Nutrition 17:77-81, 1993)