Department of Surgery, Laboratory of Anti-inflammatory Signaling and Surgical Immunology, Center of Immunity and Infection, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.
J Surg Res. 2011 Aug;169(2):257-66. doi: 10.1016/j.jss.2009.11.712. Epub 2009 Dec 9.
Alternative experimental models of hemorrhage mimic particular conditions of clinical settings and provide advantages to analyze novel resuscitation treatments. Here, we compared alternative models of hemorrhage and analyzed the effects of resuscitation with Hextend.
Adult male Sprague-Dawley rats underwent alternative models of hemorrhage: anesthetized without trauma, anesthetized with trauma, or conscious (unanesthetized) hemorrhage. Each model of hemorrhage includes three experimental groups: (C) control without hemorrhage or resuscitation treatment; (NR) animals with hemorrhage but without resuscitation; and (HX) animals with hemorrhage and resuscitation treatment with Hextend.
Conscious animals required the highest hemorrhagic volume, whereas hemorrhage with trauma required the lowest blood volume withdrawal to achieve the same arterial pressure. Conscious hemorrhage exhibited the fastest mortality, but anesthetized animals with or without trauma had similar mortality kinetic. These survival rates did not correlate with blood chemistry, hemodynamic responses, or serum TNF and HMGB1 levels. Hemorrhage in conscious animals or anesthetized animals with trauma increased serum TNF levels by approximately 2-fold compared with hemorrhage in anesthetized animals without trauma. Animals in conscious hemorrhage had similar TNF increases in all the organs, but trauma induced a specific TNF overproduction in the spleen. Resuscitation with Hextend improved survival in all the experimental models, yet its survival benefits were statistically greater in anesthetized animals with trauma. The only two markers similar to the survival benefits of Hextend were the TNF levels in the lung and liver. Hextend significantly improved survival and inhibited pulmonary and hepatic TNF levels in all the experimental models.
The survival benefits of resuscitation with Hextend depended on the experimental models and did not correlate with blood chemistry, hemodynamic, or serum cytokine levels. However, resuscitation with Hextend inhibited TNF levels in the lung and the liver with a pattern that resembled the survival benefits.
替代的出血实验模型模拟了临床环境的特定条件，并提供了分析新型复苏治疗的优势。在这里，我们比较了替代的出血模型，并分析了使用 Hextend 进行复苏的效果。
成年雄性 Sprague-Dawley 大鼠经历了替代的出血模型：未受伤的麻醉、受伤的麻醉或清醒（未麻醉）出血。每个出血模型包括三个实验组：（C）无出血或复苏治疗的对照；（NR）有出血但无复苏的动物；和（HX）有出血且用 Hextend 进行复苏治疗的动物。
清醒的动物需要最高的出血量，而创伤性出血需要最低的血液抽取量来达到相同的动脉压。清醒的出血动物表现出最快的死亡率，但有或没有创伤的麻醉动物的死亡率动力学相似。这些存活率与血液化学、血流动力学反应或血清 TNF 和 HMGB1 水平无关。与未受伤的麻醉动物相比，清醒的出血动物或有创伤的麻醉动物的出血增加了大约 2 倍的血清 TNF 水平。在所有器官中，清醒出血动物的 TNF 增加相似，但创伤诱导了脾脏中特定的 TNF 过度产生。使用 Hextend 复苏提高了所有实验模型的存活率，但在有创伤的麻醉动物中，其生存获益在统计学上更大。与 Hextend 的生存获益相似的唯一两个标志物是肺和肝脏中的 TNF 水平。Hextend 显著提高了所有实验模型的存活率，并抑制了肺和肝中的 TNF 水平。
使用 Hextend 复苏的生存获益取决于实验模型，与血液化学、血流动力学或血清细胞因子水平无关。然而，Hextend 复苏抑制了肺和肝中的 TNF 水平，其模式与生存获益相似。
