Vertrees R A, Tao W, Kramer G C, Nutt L, McDaniel L B, DeVine S D, Jesmok G, Zwischenberger J B
Department of Surgery, University of Texas Medical Branch, Galveston 77555-0528, USA.
ASAIO J. 1994 Jul-Sep;40(3):M554-9. doi: 10.1097/00002480-199407000-00060.
Tumor necrosis factor-alpha (TNF-alpha) has been implicated as causing the systemic inflammatory response to cardiopulmonary bypass (CPB) that contributes to the postoperative sequelae of coagulopathy, increased capillary permeability, leukocytosis, fever, and multiple organ dysfunction. To define the role of TNF-alpha on leukocyte populations during CPB, pigs (n = 6) were pretreated with 20 mg TNF-alpha monoclonal murine antibody before normothermic CPB (2 hr) in a blinded prospective randomized study with saline used as a control (n = 6). The leukocyte response to CPB was measured at 10, 30, 60, and 120 min during CPB and at 60 and 120 min after CPB. Repeated measures analysis of variance was performed and the null hypothesis was discarded at the 5% level. The control group displayed the typical leukocyte profile associated with CPB: and initial leukopenia (36% reduction) followed by leukocytosis (11% increase, P = 0.0001). The initial leukopenia was due to a fall in both polymorphonuclear neutrophils (33% reduced, P < 0.05) and monocytes (37% reduced, P < 0.05). In the TNF-alpha monoclonal murine antibody group the total leukocyte profile did not change significantly from baseline, (8.7% reduction to a 16% increase, P = 0.24) nor were there significant changes in populations including neutrophils and lymphocytes. In the treatment group the initial reduction in monocytes was prevented and total circulating monocytes increased during bypass. The experimental data suggest that TNF-alpha may play an important role in the early alterations in leukocyte populations associated with CPB, and TNF-alpha monoclonal murine antibody pretreatment ameliorates the leukocyte response.
肿瘤坏死因子-α（TNF-α）被认为是导致体外循环（CPB）全身炎症反应的原因，这种反应会导致术后凝血功能障碍、毛细血管通透性增加、白细胞增多、发热和多器官功能障碍等后遗症。为了确定TNF-α在CPB期间对白细胞群体的作用，在一项前瞻性随机双盲研究中，对6头猪在常温CPB（2小时）前用20毫克TNF-α单克隆鼠抗体进行预处理，以生理盐水作为对照（6头猪）。在CPB期间的10、30、60和120分钟以及CPB后60和120分钟测量白细胞对CPB的反应。进行了重复测量方差分析，原假设在5%水平被摒弃。对照组显示出与CPB相关的典型白细胞谱：最初白细胞减少（减少36%），随后白细胞增多（增加11%，P = 0.0001）。最初的白细胞减少是由于多形核中性粒细胞（减少33%，P < 0.05）和单核细胞（减少37%，P < 0.05）均下降所致。在TNF-α单克隆鼠抗体组中，白细胞总数与基线相比无显著变化（从减少8.7%到增加16%，P = 0.24），包括中性粒细胞和淋巴细胞在内的细胞群体也无显著变化。在治疗组中，单核细胞的最初减少得到预防，且在体外循环期间循环单核细胞总数增加。实验数据表明，TNF-α可能在与CPB相关的白细胞群体早期变化中起重要作用，且TNF-α单克隆鼠抗体预处理可改善白细胞反应。
