From the Department of Anesthesia, University of Texas, Houston, Texas (Z.P.); Blood Systems Research Institute, San Francisco, California (S.P.); Department of Pathology, University of Maryland, Baltimore, Maryland (M.J.F.); Mahtomedi, Minnesota (K.H.); Shock Trauma Center, University of Maryland, Baltimore, Maryland (A.V.H., R.A.K.).
J Trauma Acute Care Surg. 2016 Nov;81(5 Suppl 2 Proceedings of the 2015 Military Health System Research Symposium):S171-S176. doi: 10.1097/TA.0000000000001221.
Clinical studies have demonstrated that the early and empiric use of plasma improves survival after hemorrhagic shock. We have demonstrated in rodent models of hemorrhagic shock that resuscitation with plasma is protective to the lungs compared with lactated Ringer's solution. As our long-term objective is to determine the molecular mechanisms that modulate plasma's protective effects in injured bleeding patients, we have used human plasma in a mouse model of hemorrhagic shock. The goal of the current experiments is to determine if there are significant adverse effects on lung injury when using human versus mouse plasma in an established murine model of hemorrhagic shock and laparotomy.
Mice underwent laparotomy and 90 minutes of hemorrhagic shock to a mean arterial pressure (MAP) of 35 ± 5 mm Hg followed by resuscitation at 1× shed blood using either mouse fresh frozen plasma (FFP), human FFP, or human lyophilized plasma. Mean arterial pressure was recorded during shock and for the first 30 minutes of resuscitation. After 3 hours, animals were killed, and lungs collected for analysis.
There was a significant increase in early MAP when mouse FFP was used to resuscitate animals compared with human FFP or human lyophilized plasma. However, despite these differences, analysis of the mouse lungs revealed no significant differences in pulmonary histopathology, lung permeability, or lung edema between all three plasma groups. Analysis of neutrophil infiltration in the lungs revealed that mouse FFP decreased neutrophil influx as measured by neutrophil staining; however, myeloperoxidase immunostaining revealed no significant differences in between groups.
The study of human plasma in a mouse model of hemorrhagic shock is feasible but does reveal some differences compared with mouse plasma-based resuscitation in physiologic measures such as MAP postresuscitation. Measures of end organ function such as lung injury appear to be comparable in this acute model of hemorrhagic shock and resuscitation.
临床研究表明，早期和经验性地使用血浆可提高失血性休克后的存活率。我们在失血性休克的啮齿动物模型中证明，与乳酸林格氏液相比，用血浆复苏对肺部具有保护作用。由于我们的长期目标是确定调节受伤出血患者血浆保护作用的分子机制，因此我们在失血性休克的小鼠模型中使用了人类血浆。当前实验的目的是确定在既定的失血性休克和剖腹手术的小鼠模型中，使用人源血浆与鼠源血浆相比是否对肺损伤有重大不利影响。
小鼠接受剖腹手术和 90 分钟的失血性休克，平均动脉压（MAP）降至 35±5mmHg，然后使用 1×失血容量的鼠新鲜冷冻血浆（FFP）、人 FFP 或人冻干血浆进行复苏。休克期间和复苏的前 30 分钟记录平均动脉压。3 小时后，处死动物并收集肺部进行分析。
与使用人 FFP 或人冻干血浆相比，使用鼠 FFP 复苏动物可显著增加早期 MAP。然而，尽管存在这些差异，对小鼠肺脏的分析并未显示三种血浆组之间在肺组织病理学、肺通透性或肺水肿方面有显著差异。对肺部中性粒细胞浸润的分析表明，鼠 FFP 减少了中性粒细胞染色所测量的中性粒细胞浸润；但是，髓过氧化物酶免疫染色未显示各组之间有显著差异。
在失血性休克的小鼠模型中研究人血浆是可行的，但与基于鼠血浆的复苏相比，在生理测量方面（如复苏后的 MAP）确实存在一些差异。在这种急性失血性休克和复苏模型中，终末器官功能（如肺损伤）的测量似乎是可比的。
