THE IMPACTS OF EXPERIMENTAL NECROTIZING PANCREATITIS ON HEPATOCELLULAR ION HOMEOSTASIS AND ENERGETICS - AN IN-VIVO NUCLEAR-MAGNETIC-RESONANCE STUDY

Background. Liver dysfunction may be an early event or the end result of multiple organ dysfunction (MOD) in necrotizing pancreatitis. This study measured the early changes in hepatocellular ions and energetics associated with such conditions. Methods. Twenty-five rats, prepared with a Na-23 and P-31 double-tuned nuclear magnetic resonance surface coil secured over the dome of the liver, were randomized into 5 groups : Control, 10 and 20 minutes of total inflow ischemia, pancreatitis in duced by deoxycholic acid (DCA), and sham-DCA (saline injection). Dysp osium-TTHA(3-) solution was used to separate the intracellular and ext racellular sodium leaks. Results. In rat liver, 20 minutes of total in flow occlusion caused irreversible depletion of high-energy phosphates . Changes at 2 hours after the onset of DCA-pancreatitis are compared with changes after 20 minutes of ischemia (mean +/- SEM). Although the DCA-pancreatitis animals did not become hypotensive until 1 hour afte r the induction of pancreatitis, the changes in hepatic intracellular ions and energetics began soon after such all insult. At 2 hours after the onset of pancreatitis, hepatocellular pH(i) and [NA(+)](i) were 6 .99 +/- 0.16 and 78.4 +/- mmol/L, respectively (P<.01, compared with s ham animals). A similar pattern of changes in hepatic bioenergetics al so occurred. After the onset of pancreatis, the hepatic cytostolic pho sphorylation potential decreased with time (y = 0.654 - 0.004t, where t is time in minutes and r(2) = 0.967 and the rate of hepatic hydrolys is of adenosine triphosphate increased progressively (y = 0.702t + 91. 363, where t is time in minutes and r(2) = 0.969. These changes correl ated well with the accumulated [Na](i). Conclusions. Unresuscitated ne crotizing pancreatitis caused severe hepatocellular acidosis, profound sodium accumulation and bioenergy depletion early in its course. Thes e effects were as severe as those induced by total liver ischemia. Liv er dysfunction may be an early, not terminal, event MOD in necrotizing pancreatitis.