Department of Intensive Care Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
Crit Care Med. 2010 Feb;38(2):602-11. doi: 10.1097/CCM.0b013e3181c03f65.
Endocrine disturbances and a feeding-resistant wasting syndrome, characterized by a negative protein balance, promote delayed recovery and poor outcome of critical illness. Parenteral nutrition alone cannot counteract the hypercatabolic state, possibly in part as a result of aggravation of the hyperglycemic response to illness. In critically ill rabbits, we investigated the impact of varying amounts of intravenous glucose while maintaining normoglycemia on mortality, organ damage, and markers of catabolism/anabolism.
Prospective, randomized laboratory investigation.
University animal and molecular laboratory.
Three-month-old male rabbits.
Critically ill rabbits were randomized into a fasting group, a standard parenteral nutrition group, and two groups receiving either intermediate or high additional physiological amounts of intravenous glucose while maintained normoglycemic with insulin. These groups were compared with a hyperglycemic group and healthy rabbits. Protein and lipid load was equal for all fed groups.
Varying intravenous glucose load did not affect mortality or organ damage provided hyperglycemia was prevented. Fasted critically ill rabbits lost weight, which was attenuated by increasing intravenous glucose load. As compared with healthy rabbits, mRNA expression and/or activity of several ubiquitin-proteasome pathway components, cathepsin-L and calpain-1, was elevated in skeletal muscle of fasted critically ill rabbits. Intravenous feeding was able to counteract this response. Excessive glucose load and/or hyperglycemia, however, reduced the protective effect of feeding. Genes investigated in the diaphragm and myocardium revealed roughly a similar response. Except in the normoglycemic group with intermediate glucose load, circulating thyroid hormone and insulin-like growth factor-1 levels decreased, most pronounced in hyperglycemic rabbits.
Increasing intravenous glucose infusion within the physiological range, while maintaining normoglycemia, was safe for organ function and survival of critically ill rabbits. Concomitantly, it reduced the catabolic responses as compared with fasting. Whether this has a beneficial effect on muscle function and mass remains to be investigated.
内分泌紊乱和以蛋白质负平衡为特征的摄食抵抗性消耗综合征会促进危重病的恢复延迟和预后不良。单纯肠外营养无法对抗分解代谢亢进状态，部分原因可能是加重了疾病对血糖的反应。在危重病兔中，我们研究了在维持血糖正常的情况下，给予不同量的静脉葡萄糖对死亡率、器官损伤和分解代谢/合成代谢标志物的影响。
前瞻性、随机实验室研究。
大学动物和分子实验室。
3 月龄雄性兔。
危重病兔随机分为禁食组、标准肠外营养组和两组，在胰岛素维持血糖正常的情况下，分别给予中等或高生理量的静脉葡萄糖。这些组与高血糖组和健康兔进行比较。所有喂养组的蛋白质和脂肪负荷相同。
只要预防高血糖，静脉葡萄糖负荷的变化就不会影响死亡率或器官损伤。禁食的危重病兔体重减轻，增加静脉葡萄糖负荷可减轻体重减轻。与健康兔相比，禁食的危重病兔骨骼肌中几种泛素-蛋白酶体途径成分、组织蛋白酶-L 和钙蛋白酶-1 的 mRNA 表达和/或活性升高。静脉喂养能够抵消这种反应。然而，过多的葡萄糖负荷和/或高血糖会降低喂养的保护作用。在膈肌和心肌中研究的基因也揭示了大致相似的反应。除了血糖正常且葡萄糖负荷适中的组外，循环甲状腺激素和胰岛素样生长因子-1 水平下降，高血糖兔下降最明显。
在维持血糖正常的情况下，将静脉葡萄糖输注增加到生理范围内对危重病兔的器官功能和生存是安全的。同时，与禁食相比，它降低了分解代谢反应。这是否对肌肉功能和质量有有益的影响仍有待研究。
