Hepatic Adenine Nucleotides and DNA Synthesis during the Regenerative and Atrophic Process of the Liver Lobes after Selective Portal Vein Ligation

Abstract

Selective portal vein occlusion prior to aggressive hepatic resection is now an alternative way to decrease postoperative morbidity and mortality rates. However, the detailed changes in the hepatic energy status and DNA synthesis rate in both portal vein ligated (PVL) and nonligated (PVNL) lobes of the liver are not clear. In rats, the portal branch that supplies 70% of the liver volume was ligated, and changes in arterial ketone body ratio (AKBR), liver weight, histology, DNA synthesis rate and adenine nucleotides of the PVL and PVNL liver lobes were determined before and 1, 2, 4 and 7 days after portal vein ligation, and compared with those in sham-operated rats. The weight of the PVL lobes decreased, while that of the PVNL lobes increased depending on time. The DNA synthesis rates of the PVNL lobes were significantly higher than those in sham-operated control liver during the first 4 days with the maximal value on the 2nd day, while those of PVL lobes were essentially similar to the control values. Energy charge (EC) in both PVL and PVNL lobes significantly decreased on day 1 and recovered gradually, but with less extent in the regenerating PVNL lobes. The concentrations of total adenine nucleotides (TAN) in both the PVL and PVNL lobes were essentially similar during the first 2 days, but became significantly lower in PVL lobes after day 4. A decrease in EC preceded an increase in DNA synthesis only in the PVNL lobes, in contrast to the PVL lobes. Mitosis of hepatocytes on day 2 and subsequently enlarged lobules with an increased number of hepatocytes were histologic features in the PVNL liver. The AKBR was not correlated with hepatic energy charge of the liver. In conclusion, PVNL liver regenerates preceded by a decrease in EC and a subsequent increase in DNA synthesis keeping TAN constant, while PVL liver becomes atrophic, with a similar change in EC of the PVNL liver but ultimately decreased TAN without any change in DNA synthesis. AKBR is not a parameter reflecting the hepatic EC after portal branch ligation.

Alterations in hepatic lobar function in regenerating rat liver

“…Considering that the cytoplasmic transport (microtubules) and canalicular excretion (multidrug resistance-associated protein 2) of ICG are ATP dependent, the previously mentioned alterations may indicate a decrease in the hepatic energy status of the PVNL lobes. This observation is in accordance with the results of Kameoka et al [30] and Kucuktulu et al [31], who demonstrated that the ATP concentration and metabolically available energy pool (energy charge) of PVNL lobes significantly decreased in the early phase of liver regeneration, caused by the enormous energy consumption of cell proliferation. In the present study, mitotic activity reached its peak on the second day, when T max and C max were the most impaired.…”

Effect of Preoperative Portal Vein Embolization on Liver Volume and Hepatic Energy Status of the Nonembolized Liver Lobe in Humans

“…The liver volume changes observed in our study confirmed previous observations that PVE induces an increase in the volume of the nonembolized lobe, counterbalancing the total liver volume [1][2][3][4][5]. The volume gain of the left lobe 11 days after right PVE has been recently reported to be 136 cm 3 on average in humans [4].…”

“…The well-known effect is the hypertrophy of the portal-vein (PV)-nonembolized lobe with concomitant atrophy of the PV-deprived lobe, keeping the total liver volume essentially constant, in animals and human beings [4,5]. At the time of surgery after PVE, the PV embolized lobe is excised, which enables the remnant liver volume to be greater after hepatectomy.…”

Triggered Liver Regeneration: From Experimental Model to Clinical Implications

“…After cessation of the portal inflow, the hepatic artery - despite the HABR - cannot maintain an optimal nutritional microvascular supply and oxygen delivery to the hepatocytes [35]. As a result, in the pericentral region - the region farthest away from the portal triad -, severe hypoxia (ischemia) occurs, leading to an impairment of the mitochondrial ATP production and consequently to necrosis [36]. In parallel, the incidence of apoptotic cell death also increases, mainly at the boundary between the necrotic and intact areas (intermediate zone) [37].…”

“…Nevertheless, the energy charge of the regenerating lobes also decreases drastically due to the enormous energy consumption of cell division. The decrease in the metabolically available energy pool (energy charge) results in the inhibition of energy-consuming processes, such as the function and synthesis of CYP enzymes [36,72]. While the function of atrophying lobes remains persistently suppressed, the drug-metabolizing activity of the regenerating lobes recovers rapidly after the active phase of cell proliferation.…”