Hirofumi Ando

Effects of Intra-abdominal Hypertension on Hepatic Energy Metabolism in a Rabbit Model

BACKGROUND Intra-abdominal hypertension is known to decrease hepatic blood flow, but its effect on hepatic energy level has not described. METHODS Fifty-three rabbits were mechanically ventilated and divided into five groups. Intra-abdominal hypertension was induced by saline infusion and maintained for 30 minutes. Hepatic sinusoidal functional blood flow was evaluated by means of indocyanine green disappearance rate (ICG-K), hepatic mitochondrial redox status was evaluated by arterial ketone body ratio, and tissue energy level was evaluated by energy charge (EC). RESULTS At an intra-abdominal pressure of 20 mm Hg, ICG-K was significantly decreased, with no decrease in EC. At 30 mm Hg, hypoxemia developed and the ICG-K decreased further, with significant decreases observed in arterial ketone body ratio and EC. The latter were not increased by administration of oxygen. CONCLUSION At an intra-abdominal pressure of 20 mm Hg, a slight decrease in sinusoidal flow did not affect hepatic energy level. At 30 mm Hg, a reduced hepatic mitochondrial redox status and a decreased energy level were attributed to a decrease in sinusoidal flow in this animal model.

Effects of Ringer's acetate solution during transient hepatic inflow occlusion in rabbits

This study aimed to clarify the difference in the effects of sodium acetate and sodium lactate administration on hepatic energy metabolism during hepatic warm ischemia and reperfusion. In the first experiment, Ringers acetate (AR) or Ringers lactate (LR) solutions were administered intravenously during 20 min of hepatic inflow occlusion in rabbits. Blood gas analyses and measurements of blood pressure, pyruvate, lactate, and ketone body concentrations in arterial blood were performed until 30 min of reperfusion. Hepatic tissue adenine nucleotide concentrations were determined at the end of the experiment. With AR administration, the plasma pyruvate level and the ratio of pyruvate to lactate were significantly elevated during reperfusion. Hepatic energy charge at 30 min of reperfusion improved significantly (P < 0.001) with AR compared with LR administration. Plasma ketone body concentrations decreased markedly with LR administration, but were maintained with AR administration. In the second experiment, intravenous administration of AR or LR, hepatic ischemia, and reperfusion were similarly performed in rabbits. Ketone body concentrations were determined in arterial and vena cava blood at 0 min, 20 min of inflow occlusion, and 30 min of reperfusion. With AR administration, a large arteriovenous difference in ketone body concentrations was observed, indicating utilization in the peripheral tissues. With LR administration, no arteriovenous difference was observed. Availability of energy substrate in peripheral tissues by administration of AR is thought to decrease the metabolic load to the liver and to improve hepatic energy status during reperfusion.

Bile and bilirubin excretion in relation to hepatic energy status during hemorrhagic shock and hypoxemia in rabbits

OBJECTIVE We investigated the relation between in vivo hepatocyte excretion of bile and bilirubin and hepatic energy status in rabbit models of hemorrhagic shock and hypoxemia. DESIGN Randomized animal study. MATERIALS AND METHODS After creation of a total biliary fistula, hemorrhagic shock with mean pressure of 50 mm Hg (10 rabbits) or hypoxemia with Pao2 at 35 mm Hg (8 rabbits) was induced for 60 minutes. We determined bile flow, excretion of bilirubin and total bile acids, the plasma level of bilirubin, and arterial ketone body ratio, which reflects hepatic mitochondrial function. MEASUREMENTS AND MAIN RESULTS Both the hemorrhagic shock and the hypoxemic models showed decreases in bile flow and excretion of bilirubin and total bile acids as well as increase in the plasma level of bilirubin in association with decreases in the hepatic energy charge and the arterial ketone body ratio. CONCLUSIONS Bile flow and the excretion of bilirubin were correlated with the hepatic energy status.

Enhanced ketogenesis in the kidney during hepatic inflow occlusion with the administration of Ringer's acetate solution

BACKGROUND The blood levels of ketone bodies, which are synthesized principally in the liver, were maintained even during hepatic inflow occlusion if Ringers acetate solution (AR) was administered, resulting in an improvement of hepatic energy level in the reperfusion phase, as reported in our previous experimental study. The current study was designed to prove that the kidneys are the organs that contribute to synthesize ketone bodies during hepatic inflow occlusion if AR is administered. METHODS The arterial, central venous, renal venous, and renal tissue ketone body concentrations were determined in rabbits administered AR or Ringers lactate solution (LR) at 20 minutes of hepatic ischemia and at 30 minutes of reperfusion. The concentrations were also compared in rabbits under AR infusion with or without hepatic ischemia for 20 minutes. Statistical analyses were performed by means of ANOVA: RESULTS With AR the renal venous ketone body concentration not only was higher than that with LR (p < 0.001) but also was higher than the arterial concentration (p = 0.05). The renal tissue ketone body concentration was higher than in those with LR (p < 0.001) and also than in those without occlusion (p < 0.001). CONCLUSIONS Ketogenesis is enhanced in the kidney and may compensate for hepatic loss of ketogenic function during hepatic inflow occlusion under AR administration.

Effects of platelet-activating factor antagonist E5880 on intrahepatic and systemic metabolic responses to transient hepatic inflow occlusion and reperfusion in the rabbit.

Abstract. We investigated the effects of pretreatment with a potent platelet-activating factor (PAF) receptor antagonist (E5880) on the changes in hepatic and systemic metabolism induced by transient hepatic ischemia and reperfusion. Sixty-five rabbits were assigned to four groups that either did or did not undergo a period of hepatic ischemia and reperfusion with or without pretreatment. E5880 was administered intraportally 1 minute prior to inflow occlusion. Twenty minutes of warm ischemia was followed by 30 minutes of reperfusion. Blood gas analyses and measurements of levels of arterial pyruvate, lactate, and ketone bodies, arterial and portal ammonia and endotoxin, and intrahepatic adenine nucleotide, pyruvate, and lactate were performed. Results were analyzed by either ANOVA or chi-square analysis. Hepatic tissue ATP and energy charge levels were significantly increased and the AMP level was significantly decreased after 30 minutes of reperfusion in the pretreatment group compared to those without pretreatment. At the same time, parameters reflecting hepatic mitochondrial function, such as the arterial ketone body ratio and arterial ammonia level, improved, although they were not statistically significant. No difference was observed for parameters reflecting systemic changes, such as arterial blood gas values and pyruvate and lactate levels. PAF is thought to mediate metabolic changes after hepatic ischemia and reperfusion. PAF released in the liver may exert local effects, which appear to be attenuated by pretreatment with E5880. Systemic metabolic changes seen after hepatic ischemia and reperfusion may be mediated by factors other than PAF.