Department of General and Visceral Surgery, University Hospital of Muenster, Muenster, Germany.
J Surg Res. 2013 Jan;179(1):e167-75. doi: 10.1016/j.jss.2012.01.042. Epub 2012 Apr 1.
Sepsis and systemic inflammatory response syndrome (SIRS) continue to represent critical conditions with persistently high mortality and continue to need experimental and clinical research. We developed a rat model of gram-positive and gram-negative SIRS/sepsis with in vivo visualization of the pulmonary microcirculation to evaluate the optimal dosage and application path for SIRS/sepsis-inducing agents.
Male Sprague-Dawley rats (n = 8 per group) were assigned to control, lipopolysaccharide (LPS), alphatoxin, or living Staphylococcus aureus (strain 68/50) groups. SIRS/sepsis was induced by intraperitoneal injection of the differing agents. The onset of SIRS was determined through human sepsis parameters and fluorescence video microscopy-based measurement of platelet and leukocyte velocity within the pulmonary vascular system (injection of 5 × 10(6) calcein AM-labeled nonactivated platelets; leukocytes labeled in vivo by rhodamine).
The optimal dosage to induce SIRS was 30 mg/250 g body weight for LPS (bolus injection) and 60 μg/250 g body weight for alphatoxin (2 h continuous perfusion). Sepsis was not achieved by injection of living S. aureus. The onset of SIRS was seen after 2-5 h for LPS and after 2-4 h for alphatoxin after intraperitoneal administration with a significantly increased heart rate, breathing rate, and body temperature (P < 0.05) and significantly decreased cell velocity (P < 0.05).
Our study represents an effective approach for a gram-negative (LPS) and gram-positive (alphatoxin) SIRS model to mimic human sepsis. Human sepsis-based criteria were used to define SIRS in our rats to achieve an optimal analogy for the human system. In our model, higher dosages were needed for SIRS induction than have been previously reported. The resulting, considerable heterogeneity of current SIRS-inducing models suggests that additional studies in this field are required to define standard procedures.
脓毒症和全身炎症反应综合征（SIRS）仍然是死亡率持续居高不下的危急情况，需要进行实验和临床研究。我们建立了一种革兰氏阳性和革兰氏阴性 SIRS/脓毒症大鼠模型，通过对肺微循环的体内可视化来评估 SIRS/脓毒症诱导剂的最佳剂量和应用途径。
雄性 Sprague-Dawley 大鼠（每组 n = 8）分为对照组、脂多糖（LPS）组、α-毒素组或活金黄色葡萄球菌（菌株 68/50）组。通过腹腔注射不同的试剂诱导 SIRS/脓毒症。通过人类脓毒症参数和基于荧光视频显微镜测量肺血管系统中血小板和白细胞速度来确定 SIRS 的发作（注射 5×10^6 个 calcein AM 标记的非激活血小板；白细胞在体内用 rhodamine 标记）。
诱导 SIRS 的最佳剂量为 LPS 30 mg/250 g 体重（推注）和α-毒素 60 μg/250 g 体重（2 小时连续灌注）。活金黄色葡萄球菌注射不能引起脓毒症。腹腔注射 LPS 后 2-5 小时，α-毒素后 2-4 小时出现 SIRS 发作，心率、呼吸频率和体温明显升高（P < 0.05），细胞速度明显降低（P < 0.05）。
我们的研究代表了一种有效的革兰氏阴性（LPS）和革兰氏阳性（α-毒素）SIRS 模型，可模拟人类脓毒症。我们在大鼠中使用基于人类脓毒症的标准来定义 SIRS，以实现对人类系统的最佳模拟。在我们的模型中，诱导 SIRS 所需的剂量高于以前报道的剂量。目前 SIRS 诱导模型的这种相当大的异质性表明，需要在该领域进行更多的研究来定义标准程序。
