LIVER-REGENERATION AFTER PARTIAL-HEPATECTOMY IN THE RAT - SEQUENTIAL EVENTS MONITORED BY P-31-NUCLEAR MAGNETIC-RESONANCE SPECTROSCOPY AND BIOCHEMICAL-STUDIES

BACKGROUND: Little data exist wherein both the P-31 nuclear magnetic r esonance (NMR) signals and biochemical changes associated with hepatic regeneration after a 70% hepatic resection have been assessed simulta neously. EXPERIMENTAL DESIGN: Two groups of rats were used: one group underwent a 70% partial hepatectomy and the second underwent a sham op eration. Both groups were followed sequentially for 199 hours by in vi vo serial P-31-NMR spectroscopy of the liver and its phospholipid extr acts. Liver injury and function were assessed by biochemical means. RE SULTS: After surgery, a significant reduction in ATP and an increase i n the phosphomonoester signal for the hepatectomized animals were note d as compared with the controls (p < 0.05). The phosphodiester content of the liver in the hepatectomized rats declined to nonmeasurable amo unts in vivo. The nadir of ATP occurred 72 hours after surgery. The ar ea of the phosphomonoester relative to an external reference of methyl enediphosphonic acid peak increased steadily over the first 96 hours, whereas that of the area ratio of the inorganic phosphate/methylenedip hosphonic increased over the first 72 hours posthepatectomy. The intra cellular pH declined sharply in the first 3 days, followed by a gradua l recovery over the next 5 days. Little change in the intracellular pH was observed for the control animals. A significant increase in the a rea of the phosphorylethanolamine relative to an internal reference of methylenediphosphonic and a reduction in the glycerophosphorylethanol amine and glycerophosphorylcholine peaks were noted during the first f our post-hepatectomy days as measured by P-31-NMR of perchloric acid l iver extracts (p < 0.05). CONCLUSIONS: It has been found that a concer ted reduction in the intracellular ATP and intracellular pH coupled wi th an increase in inorganic phosphate and high levels bf phosphoryleth anolamine occur as a result of hepatic regeneration and the physiologi c changes induced. These data demonstrated that a coordinated pattern of biochemical changes occur with: and after hepatic regeneration. Mor eover, NMR spectroscopy demonstrates an increase in phosphomonoesters and a decline in phosphodiesters during hepatic regeneration. These me asures and, more specifically, the ratio of these two lipid classes ma y provide a biochemical snapshot of the regeneration status of the liv er.