Conner W C, Gallagher C M, Miner T J, Tavaf-Motamen H, Wolcott K M, Shea-Donohue T
Department of Surgery, Walter Reed Army Medical Center, Washington, DC,USA.
J Surg Res. 1999 Jun 1;84(1):24-30. doi: 10.1006/jsre.1999.5598.
Multiple organ failure after serious injury or illness is a major determinant of mortality. An initial insult is believed to "prime" circulating neutrophils and induce systemic inflammation. Thereafter, a second insult will precipitate distant organ injury. The aim of these studies was to evaluate circulating neutrophil function after mesenteric ischemia-reperfusion to determine the neutrophil "priming state," a quantitative and clinically useful predictor of multiple organ failure.
Anesthetized Sprague-Dawley rats underwent superior mesenteric artery occlusion for 30 min or sham operation and were euthanized after 2, 6, or 24 h of reperfusion. Control animals had blood taken without any intervention. To determine changes in lung capillary permeability, another group of rats received Evan's blue, a dye that binds albumin, 1 h before sacrifice. Flow cytometric analysis was performed on 5 million white blood cells after removal of red cells by lysis and centrifugation. Neutrophil number, oxidative burst, and CD18 expression were measured.
The number of circulating neutrophils was elevated similarly in rats subjected to sham operation or ischemia-reperfusion. Oxidative burst potential was increased at 2 h, maximum at 6 h, and normal at 24 h after reperfusion, but not in sham rats. CD18 expression was similar in all groups. There was a significant temporal correlation between the "priming state" of the circulating neutrophil, defined as the product of the neutrophil number times oxidative burst, and lung leak.
The neutrophil "priming state" may allow the clinician to better predict those patients at greatest risk for multiple organ failure.
严重创伤或疾病后的多器官功能衰竭是死亡率的主要决定因素。最初的损伤被认为会“激活”循环中的中性粒细胞并引发全身炎症。此后,第二次损伤将促使远处器官损伤。这些研究的目的是评估肠系膜缺血再灌注后循环中性粒细胞的功能,以确定中性粒细胞的“激活状态”,这是一种多器官功能衰竭的定量且具有临床实用性的预测指标。
将麻醉后的Sprague-Dawley大鼠进行肠系膜上动脉闭塞30分钟或假手术,并在再灌注2、6或24小时后实施安乐死。对照动物在未进行任何干预的情况下采血。为了确定肺毛细血管通透性的变化,另一组大鼠在处死前1小时注射伊文思蓝,一种可与白蛋白结合的染料。通过裂解和离心去除红细胞后,对500万个白细胞进行流式细胞术分析。测量中性粒细胞数量、氧化爆发和CD18表达。
假手术或缺血再灌注大鼠的循环中性粒细胞数量同样升高。再灌注后2小时氧化爆发潜能增加,6小时达到峰值,24小时恢复正常,但假手术大鼠未出现此情况。所有组的CD18表达相似。循环中性粒细胞的“激活状态”(定义为中性粒细胞数量乘以氧化爆发的乘积)与肺渗漏之间存在显著的时间相关性。
中性粒细胞“激活状态”可能使临床医生能够更好地预测那些发生多器官功能衰竭风险最高的患者。