Background. Multiple organ failure (MOF) is the most serious complication i
n severe acute pancreatitis, contributing to its high mortality. It has bee
n suggested that changes of high-energy phosphates, intracellular pH, and i
ntracellular cation homeostasis are closely related to hepatocellular injur
y associated with MOF.
Methods. Phosphorus metabolites, intracellular pH (pH(i)), and intracellula
r Na+ concentration ([Na+](i)) were measured in rat livers in vivo using P-
31 and Na-23 NMR spectroscopy after deoxycholic acid (DCA)-induced pancreat
itis or intraperitoneal injection (ip) of pancreatitis-induced ascitic flui
d (PAF).
Results. Two hours after induction of DCA-pancreatitis, the liver experienc
ed significant intracellular acidosis (pH(i) = 6.99 +/- 0.16) and sodium lo
ading (75 +/- 9 mM) and a reduction in its energy state (beta-ATP/P-i = 0.2
+/- 0.03 and P-i = 164 +/- 12). Although ip injection of PAF into healthy
rats did not induce systemic hypotension, the livers under these conditions
also developed severe disturbances in hepatocellular ion homeostasis and d
epletion of its bioenergetics. The longer the abdomen was exposed to the PA
F, the worse the changes were. At 3 h after ip injection of PAF, hepatic [N
a+](i) significantly increased (42 +/- 3 mM) along with a significant decre
ase in pH(i) (7.30 +/- 0.03). At 6 h after ip injection of PAF, the hepatic
beta-ATP/P-i ratio decreased to 0.34 +/- 0.05 and P-i increased to 97 +/-
27.
Conclusions. PAF induced severe hepatocellular acidosis, rapid accumulation
of hepatic intracellular sodium, impaired hepatic cytosolic phosphorylatio
n potential, and increased hepatic utilization of ATP. These effects may ac
count for the eventual development of liver dysfunction associated with nec
rotizing pancreatitis. (C) 1999 Academic Press.