The concentrations of acetoacetate, beta-hydroxybutyrate, and adenine nucleotides, and the mitochondrial phosphorylative activities, induced by cecal ligation and punctured in the liver of septic rats, were determined. The concentrations of glucose, free fatty acids (FFA), and free amino acids in arterial blood were also studied along with ketone body concentrations. Hepatic energy charge levels decreased from 0.84 to 0.77 at 12h after the induction of sepsis (P less than 0.01) and to 0.60 at 18h (P less than 0.001). Mitochondrial phosphorylative activity was enhanced at 6h (P less than 0.001) and decreased at 18h later. Ketone body concentrations in the liver and the arterial blood decreased concomitant with the decrease in hepatic energy charge. The mitochondrial redox state increased significantly at 12 and 18h after the induction of sepsis (P less than 0.01) concomitant with a marked decrease in the concentrations of ketone bodies (P less than 0.01). Blood glucose levels remained within normal limits except for a transient increase at 6h, but plasma FFA levels decreased (P less than 0.01). The plasma concentrations of aromatic amino acids (P less than 0.001), proline, and alanine (P less than 0.05) increased slightly at 18h. It is suggested that the ketogenic capacity of the liver is inhibited during sepsis, but that the liver maintains gluconeogenesis at relatively normal levels until a more advanced stage of sepsis.

Liver mitochondrial membrane potential was assessed during regeneration following partial hepatectomy in rabbits. Absorbance change of safranine O per milligram of mitochondrial protein was used to evaluate mitochondrial membrane potential. Absorbance change was calibrated to the membrane potential in millivolts produced by valinomycin-induced potassium diffusion potential. At 24 hr after hepatectomy, absorbance change of safranine O per milligram of mitochondrial protein increased from 15.0 +/- 2.2 X 10(-3) to 37.4 +/- 3.3 X 10(-3) per mg (p less than 0.005). This represents a mitochondrial membrane potential increase from 77.0 +/- 4.6 to 124.4 +/- 6.7 mV. Phosphorylative activity increased from 59.9 +/- 5.0 to 106.1 +/- 7.4 nmoles ATP synthesized per mg per min (p less than 0.005). The enhancement of phosphorylative activity was closely linked to the elevation in liver mitochondrial membrane potential (r = 0.77, p less than 0.005). We suggest that elevation of mitochondrial membrane potential, coupled with enhanced oxidative and phosphorylative activities, plays an important role in the regeneration process following hepatectomy.

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To clarify the effects of partial ischemia and reflow on the mitochondrial metabolism of the rat liver, the afferent vessels supplying the left lateral and left half of medial lobes were occluded and then reperfused after given time periods of ischemia (30, 60, 90 and 120 min, groups A, B, C and D, respectively). Samplings were taken at 0, 10 and 60 min after reperfusion. The energy charge levels of ischemic lobes decreased rapidly from 0.85 ± 0.01 in the sham group to 0.38 ± 0.11, 0.35 ± 0.07 and 0.34 ± 0.06 in groups B, C and D, respectively. The phosphorylative activities of mitochondria isolated from ischemic lobes decreased gradually along with the time of ischemia. The reversal of mitochondrial function and energy charge levels following reperfusion was noted in groups A and B. In nonischemic lobes, the phosphorylation rate (nmol ATP/mg/min) increased from 90 ± 6 in sham group to 125 ± 12 and 130 ± 9; 131 ± 5 and 130 ± 6; 123 ± 6 and 122 ± 17, and 138 ± 6 and 138 ± 13 at 10 and 60 min after reflow in groups A, B, C and D, respectively (p < 0.05). The energy charge level of nonischemic lobes decreased from 0.85 ± 0.01 of sham group to 0.80 ± 0.03 in group D (p < 0.05). From these results, it is concluded that the transitional zone for the reversal of mitochondrial function and energy metabolism following prolonged liver ischemia appears at around 60 min. It is suggested that there exist some mechanism(s) which lead to an enhancement of mitochondrial function in nonischemic lobe after reflow.