Energy deficit in surgery on the examples of cholestasis and massive liver resection

E. I. Galperin
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Abstract

The paper is dedicated to the energy processes associated with diseases in living organisms. Experiments involved 151 rats. Liver tissue was taken to determine its energy state in cholestasis (common bile duct ligation) and after resection of 60% and 80% of the parenchyma (without cholestasis). Adenine nucleotides (ATP, ADP, and AMP) and activity of gluconeogenesis enzymes were studied in cholestasis every 3 days for 15 days and after liver resection – every 6 hours for 3 days. Particular attention was paid to the energy deficit in liver tissue. A certain level of energy deficit n agent of metabolic stress. The experiments revealed that the energy deficit in the liver tissue increased by 15% by day 6 of cholestasis and by 48–50% of the initial energy level by days 12–15. The increase in energy deficit in liver tissue inversely correlated with the decrease in the activity of gluconeogenesis enzymes – by day 15 glucose-6- phosphate dehydrogenase reduced by 44% and isocitrate dehydrogenase – by 48% of the initial energy level. Decompression after 15 days from the onset of cholestasis was followed by an increase in energy deficit by 15%, as compared to the initial energy level, within 3–5 days. No development of metabolic stress was evidenced by a decrease in the activity of gluconeogenesis enzymes. After 12 hours after resection of 60% and 80% of the liver parenchyma, the liver energy deficit in both groups accounted for 50% of the initial energy level. After resection of 60% of the liver parenchyma, the energy deficit decreased rapidly: after 24 hours to 30%, after 72 hours to 11%; 2 rats out of 30 died during this period. After 12 hours after resection of 80% of the liver parenchyma, the energy deficit rose sharply: after 24 hours to 70% of the initial energy level. This led to the death of 26 animals out of 31. Both groups of animals demonstrated an inverse relationship between the decreased amount of energy used for hepatocyte function and the increased activity of key enzymes of gluconeogenesis. The obtained results suggest that in both groups of animals, metabolic stress developed after liver resection, however, after resection of 80% of the organ parenchyma, it “choked” due to the deficit of remnant hepatocytes. Most of the energy was spent for the development of regeneration. Metabolic stress and regeneration develop simultaneously. A deficit of 50% of energy in liver tissue with a further increase may indicate a critical condition, both in cholestasis and after a massive resection. The research into energy changes in cholestasis and after massive liver resections reveals new patterns of internal processes of the body.
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以胆汁淤积症和大块肝脏切除术为例说明外科手术中的能量不足问题
该论文致力于研究与生物体疾病相关的能量过程。实验涉及 151 只大鼠。在胆汁淤积(胆总管结扎)和切除 60% 和 80% 的肝实质(无胆汁淤积)后,取肝脏组织测定其能量状态。在胆汁淤积的15天内,每3天对腺嘌呤核苷酸(ATP、ADP和AMP)和葡萄糖生成酶的活性进行了研究;在肝切除的3天内,每6小时对腺嘌呤核苷酸(ATP、ADP和AMP)和葡萄糖生成酶的活性进行了研究。研究特别关注肝组织的能量缺失情况。一定程度的能量不足是新陈代谢压力的表现。实验表明,胆汁淤积第 6 天时,肝组织的能量不足增加了 15%,第 12-15 天时,增加了初始能量水平的 48-50%。肝组织能量不足的增加与葡萄糖生成酶活性的降低成反比--到第15天,葡萄糖-6-磷酸脱氢酶的活性降低了44%,异柠檬酸脱氢酶的活性降低了初始能量水平的48%。胆汁淤积症发生 15 天后,能量下降,随后在 3-5 天内,能量缺口比初始能量水平增加 15%。葡萄糖生成酶活性的降低并不能证明出现了新陈代谢压力。切除 60% 和 80% 的肝实质 12 小时后,两组的肝脏能量缺失均占初始能量水平的 50%。切除 60% 的肝实质后,能量不足迅速下降:24 小时后降至 30%,72 小时后降至 11%;在此期间,30 只大鼠中有 2 只死亡。切除 80% 的肝实质 12 小时后,能量不足急剧上升:24 小时后上升到初始能量水平的 70%。这导致 31 只动物中有 26 只死亡。两组动物都显示,肝细胞功能所需的能量减少与葡萄糖生成关键酶的活性增加之间存在反比关系。结果表明,两组动物在肝脏切除后都出现了新陈代谢压力,但在切除 80% 的器官实质后,由于残余肝细胞的缺乏,肝脏出现了 "窒息"。大部分能量被用于发展再生。代谢压力和再生是同时发生的。肝脏组织能量不足 50%,并进一步增加,这可能预示着胆汁淤积症和大规模切除术后的危急情况。对胆汁淤积症和肝脏大面积切除术后能量变化的研究揭示了人体内部过程的新模式。
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