Pathophysiological Response of Cytokines and Vasoactive Agents in Patients Undergoing Total Gastrectomy Masaya Shito, Masakazu Ueda, Go Wakabayashi, Masao Endo and Masaki Kitajima From the Department of Surgery, Keio University School of Medicine, Tokyo, Japan Eur J Surg 1998; 164: 115–118 ABSTRACT Objective: To investigate the involvement of vasoactive agents, endothelin (ET)-1, and atrial natriuretic peptide (ANP), and the responses of cytokines in patients undergoing total gastrectomy. Design: Prospective study. Setting: University hospital, Japan. Subjects: 20 patients with advanced gastric cancer who had undergone total gastrectomy with lymph node dissection. Interventions: Serum or plasma samples collected on the day before the operation, at the time of skin closure, and on postoperative days 1, 3, 5, and 7. Main outcome measures: Concentrations of acute phase reactants, cytokines (interleukin (IL)-1, tumour necrosis factor (TNF) and interleukin (IL)-6), and vasoactive agents (ET-1 and ANP). Results: There were significant increases in concentrations of IL-6 and acute phase reactants postoperatively. ET-1 and ANP concentrations did not change significantly. Conclusion: There was no correlation between concentrations of the vasoactive agents ET-1 and ANP, and those of acute phase reactants or cytokines in serum or plasma in patients undergoing total gastrectomy. Key words: IL-1, IL-6, TNF, ET-1, ANP. INTRODUCTION Many mediators and hormones act synergistically to maintain homeostasis in patients undergoing surgical stress, and the acute phase reaction is mediated by cytokines and hormones (2, 7, 12). In our experience the clinical features of various types of surgical stress differ; these differences were thought to depend on mediators, but their role in patients undergoing abdominal operations is controversial. We have previously reported that vasoactive agents, endothelin (ET)-1 and atrial natriuretic peptide (ANP), have an important role in various types of surgical stress (1, 9, 17, 19, 20). Serum or plasma concentra- tions of cytokines and vasoactive agents increase after a major operation (6, 8, 13, 18). Although they have been reported to stimulate each other’s production in vitro and in vivo (16, 22, 23), their correlations and interactions in abdominal operations remain to be clarified. To investigate the involvement and interaction between cytokines and vasoactive agents in the physiological response to surgical operations, we analysed the postoperative concentrations of acute phase reactants, cytokines, endothelin (ET)-1 and atrial natriuretic peptide (ANP) in 20 patients undergoing total gastrectomy with lymph node dissection. PATIENTS AND METHODS The study was approved by the Human Subjects Committee of Keio University Hospital, and informed consent was obtained from the patients or their nearest relatives. Twenty patients (14 men and 6 women, mean (SD) age 57.5 (10.4) years, duration of operation 295 (54) minutes, blood loss 572 (239) g) with advanced gastric cancer who were admitted to the department of surgery, Keio University Hospital and underwent total gastrectomy with lymph node dissection were selected for this study. No patient had any apparent inflamma- tory conditions before the operation and there were no serious postoperative complications. Venous blood samples were collected on the day before the operation, at the time of skin closure, and on postoperative days 1, 3, 5, and 7. Until they were analysed for concentrations of interleukin (IL)-1 , tumour necrosis factor (TNF) , interleukin (IL)-6, C- reactive protein (CRP), and pancreatic secretory trypsin inhibitor (PSTI), samples were immediately centrifuged (at 1500 g for 10 minutes at 4°C) and the serum was stored at 20°C. Until they were analysed for polymorphonuclear leucocyte (PMN)-elastase, ET- 1, and ANP, the collected blood was placed in chilled glass tubes containing EDTA (0.1 mg/ml) and apro- tinin (500 KIU/ml), and stored at 70°C. 1998 Scandinavian University Press. ISSN 1102–4151 Eur J Surg 164 ORIGINAL ARTICLE