Chang C G, Van Way C W, Dhar A, Helling T, Hahn Y
Department of Surgery, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, 64111, USA.
J Surg Res. 2000 Aug;92(2):171-6. doi: 10.1006/jsre.2000.5857.
Hemorrhagic shock produces a marked decrease in hepatic ATP, adenylate energy charge, and total adenosine nucleotides. This is followed by slow recovery to normal levels after resuscitation. Nucleotide metabolites are increased following shock and resuscitation. Previous experimental work has shown that supraphysiologic doses of insulin have salutary effects in animals with hemorrhagic shock and in cardiac patients. It appears that insulin causes increased availability of glucose and energy-producing substrates. This study examined whether resuscitation with glucose and insulin after hemorrhagic shock would alter the changes previously seen to occur in hepatic ATP levels, adenylate energy charge, or nucleotide metabolites.
Male Sprague-Dawley rats were bled to a mean arterial blood pressure of 40 mm Hg for 30 min. They were then resuscitated with the shed blood and one of three fluids: (1) lactated Ringer's, (2) lactated Ringer's with 10% glucose, (3) lactated Ringer's with 10% glucose + 6 units/kg regular insulin. Liver biopsies were obtained prior to shock (baseline), after 30 min of shock (shock), and 90 min after resuscitation (90 min). Tissue levels of ATP, ADP, AMP, adenosine, inosine, hypoxanthine, and xanthine were measured. Serum at 90 min was evaluated for potassium, glucose, and tumor necrosis factor alpha (TNF-alpha).
The insulin-treated group had significantly increased hepatic ATP and energy charge following resuscitation compared with the other two groups. The insulin group also exhibited significant hypoglycemia. Total adenine nucleotides (ATP, ADP, and AMP) were significantly elevated 90 min postresuscitation in the insulin group. Mean blood pressures throughout the experiment were not significantly different among groups. TNF-alpha was highest in the insulin-treated group, but this was not significant.
Resuscitation with insulin and dextrose significantly increased hepatic ATP and adenylate energy charge after hemorrhagic shock in rats. Total nucleotide pool levels were not different between groups, indicating that there was a shift of the equilibrium away from the metabolites toward ATP and ADP in the insulin-treated group. Insulin treatment had no significant effect on blood pressure or TNF-alpha. However, it caused significant hypoglycemia and hypokalemia.
失血性休克会导致肝脏三磷酸腺苷（ATP）、腺苷酸能量荷及总腺苷核苷酸显著减少。复苏后这些指标会缓慢恢复至正常水平。休克及复苏后核苷酸代谢产物会增加。此前的实验研究表明，超生理剂量的胰岛素对失血性休克动物及心脏病患者有益。胰岛素似乎能增加葡萄糖及产能量底物的可利用性。本研究旨在探究失血性休克后用葡萄糖和胰岛素进行复苏是否会改变之前观察到的肝脏ATP水平、腺苷酸能量荷或核苷酸代谢产物的变化。
将雄性Sprague-Dawley大鼠放血，使平均动脉血压降至40mmHg并维持30分钟。然后用放出的血液及以下三种液体之一进行复苏：（1）乳酸林格氏液；（2）含10%葡萄糖的乳酸林格氏液；（3）含10%葡萄糖+6单位/千克正规胰岛素的乳酸林格氏液。在休克前（基线）、休克30分钟后（休克）及复苏后90分钟（90分钟）获取肝脏活检样本。测量组织中ATP、二磷酸腺苷（ADP）、一磷酸腺苷（AMP）、腺苷、肌苷、次黄嘌呤和黄嘌呤的水平。评估复苏后90分钟时血清中的钾、葡萄糖及肿瘤坏死因子α（TNF-α）水平。
与其他两组相比，胰岛素治疗组复苏后肝脏ATP及能量荷显著增加。胰岛素组还出现显著低血糖。胰岛素组复苏后90分钟时总腺嘌呤核苷酸（ATP、ADP和AMP）显著升高。整个实验过程中各组平均血压无显著差异。胰岛素治疗组TNF-α水平最高，但差异不显著。
失血性休克后用胰岛素和葡萄糖进行复苏可显著增加大鼠肝脏ATP及腺苷酸能量荷。各组总核苷酸池水平无差异，表明胰岛素治疗组的平衡从代谢产物向ATP和ADP转移。胰岛素治疗对血压或TNF-α无显著影响。然而，它导致了显著的低血糖和低钾血症。
