An Ovine Model of Hyperdynamic Endotoxemia and Vital Organ Metabolism.
An Ovine Model of Hyperdynamic Endotoxemia and Vital Organ Metabolism.
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DOI：
10.1097/shk.0000000000000904
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发表时间：
2018-01
期刊：
影响因子：
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通讯作者：
Fraser JF
中科院分区：
文献类型：
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作者：
Byrne L;Obonyo NG;Diab S;Dunster K;Passmore M;Boon AC;Hoe LS;Hay K;Van Haren F;Tung JP;Cullen L;Shekar K;Maitland K;Fraser JF
内毒素血症的动物模型经常被用来了解脓毒症的病理生理和测试新的治疗方法。然而，常用的内毒素血症实验模型与临床败血症之间存在重要差异。与临床的高动力休克相比，内毒素血症的动物模型经常产生低动力休克。这种差异可能夸大了灌注不足作为器官功能障碍的一个致病因素的重要性。本研究旨在建立高动力内毒素血症的绵羊模型，并评估是否有证据表明重要器官的氧化代谢受损。在8只羊的大脑、心脏、肝脏、肾脏和动脉循环中植入了微透析导管。用递增剂量的内毒素输注4小时诱导休克。3小时后给予去甲肾上腺素和抗利尿激素支持。动物内毒素血症后监测12小时。采集血样检测血红蛋白、白细胞计数、肌酐和促炎细胞因子（il -1 β、IL-6和IL-8）。内毒素输注成功地引起了分布性休克，平均动脉压由84.5±12.8mmHg降至49±8.03 mmHg（p<0.001）。心脏指数由3.33±0.56 l/min/m2降至2.89l±0.36 l/min/m2，维持在正常范围内（p=0.0845）。乳酸/丙酮酸比值在心脏、脑、肾和动脉循环中均无明显异常。肝脏微透析样品显示持续高乳酸/丙酮酸比值（平均37.9±3.3）。递增剂量的内毒素输注成功地产生了高动力休克。有证据表明肝脏氧化代谢受损，表明内脏灌注受损。这可能是导致多器官功能障碍和死亡的一个可改变的因素。
Animal models of endotoxemia are frequently used to understand the pathophysiology of sepsis and test new therapies. However, important differences exist between commonly used experimental models of endotoxemia and clinical sepsis. Animal models of endotoxemia frequently produce hypodynamic shock in contrast to clinical hyperdynamic shock. This difference may exaggerate the importance of hypoperfusion as a causative factor in organ dysfunction. This study sought to develop an ovine model of hyperdynamic endotoxemia and assess if there is evidence of impaired oxidative metabolism in the vital organs. Eight sheep had microdialysis catheters implanted into the brain, heart, liver, kidney and arterial circulation. Shock was induced with a 4hr escalating dose infusion of endotoxin. After 3hrs vasopressor support was initiated with noradrenaline and vasopressin. Animals were monitored for 12hrs after endotoxemia. Blood samples were recovered for haemoglobin, white blood cell count, creatinine and proinflammatory cytokines (IL-1Beta, IL-6 & IL-8). The endotoxin infusion was successful in producing distributive shock with the mean arterial pressure decreasing from 84.5 ± 12.8mmHg to 49 ± 8.03 mmHg(p<0.001). Cardiac index remained within the normal range decreasing from 3.33 ± 0.56 l/min/m2 to 2.89l ± 0.36 l/min/m2 (p=0.0845). Lactate/pyruvate ratios were not significantly abnormal in the heart, brain, kidney or arterial circulation. Liver microdialysis samples demonstrated persistently high lactate/pyruvate ratios (mean 37.9±3.3). An escalating dose endotoxin infusion was successful in producing hyperdynamic shock. There was evidence of impaired oxidative metabolism in the liver suggesting impaired splanchnic perfusion. This may be a modifiable factor in the progression to multiple organ dysfunction and death.