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 and 31P 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 induced by deoxycholic acid (DCA), and sham- DCA (saline injection). Dysprosium-TTHA3 solution was used to separate the intracellular and extracellular sodium peaks. Results. In rat liver, 20 minutes of total inflow 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 after the induction of pancreatitis, the changes in hepatic intracellular ions and energetics began soon after such an insult. At 2 hours after the onset of pancreatitis, hepatocellular pHi and [NA +](i) were 6.99 ± 0.16 and 78.4 ± mmol/L, respectively (P<101, compared with sham animals). A similar pattern of changes in hepatic bioenergetics also occurred. After the onset of pancreatitis, the hepatic cytostolic phosphorylation potential decreased with time (y=0.654 - 0.004t, where t is time in minutes and r2 = 0. 967 and the rate of hepatic hydrolysis of adenosine triphosphate increased progressively (y = 0.702t + 91.363, where t is time in minutes and r2 = 0. 969. These changes correlated well with the accumulated [Na](i). Conclusions. Unresuscitated necrotizing pancreatitis caused severe hepatocellular acidosis, profound sodium accumulation, and bioenergy depletion early in its course. These effects were as severe as those induced by total liver ischemia. Liver dysfunction may be an early, not terminal, event of MOD in necrotizing pancreatitis.
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