Zurek-Leffers Finnja Marie, Lehmann Florian, Brabenec Laura, Kintrup Sebastian, Hellenthal Katharina E M, Mersjann Kira, Kneifel Felicia, Hessler Michael, Arnemann Philip-Helge, Kampmeier Tim-Gerald, Ertmer Christian, Kellner Patrick, Wagner Nana-Maria
Department for Anaesthesiology, Intensive Care and Pain Medicine, University Hospital Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.
Department of General, Visceral and Transplant Surgery, University Hospital Münster, Münster, Germany.
Intensive Care Med Exp. 2023 Jun 2;11(1):31. doi: 10.1186/s40635-023-00513-7.
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Mortality of patients with sepsis is high and largely unchanged throughout the past decades. Animal models have been widely used for the study of sepsis and septic shock, but translation into effective treatment regimes in the clinic have mostly failed. Pigs are considered as suitable research models for human diseases due to their high comparability and similarity to human anatomy, genetics, and the immune system. We here evaluated the previously reported models of septic shock in pigs and established a novel model of polymicrobial sepsis that meets the clinical criteria of septic shock in pigs.
The literature search was performed using the keywords "pig", "sepsis" and "septic shock". For the establishment of septic shock in n = 10 German landrace pigs, mechanical ventilation was initiated, central venous and arterial lines and invasive hemodynamic monitoring via pulse contour cardiac output measurement (PiCCO) established. Peritoneal polymicrobial faecal sepsis was induced by application of 3 g/kg body weight faeces into the abdominal cavity. Septic shock was defined according to the third international consensus definitions (Sepsis-3). Upon shock, pigs underwent the 1-h bundle for the treatment of human sepsis. Cytokine levels were measured by ELISA.
Published porcine sepsis models exhibited high methodological variability and did not meet the clinical criteria of septic shock. In our model, septic shock developed after an average of 4.8 ± 0.29 h and was associated with a reproducible drop in blood pressure (mean arterial pressure 54 ± 1 mmHg) and significant hyperlactatemia (3.76 ± 0.65 mmol/L). Septic shock was associated with elevated levels of interleukin-6 (IL6) and initial cardiac depression followed by a hyperdynamic phase with significant loss of systemic vascular resistance index after initial resuscitation. In addition, organ dysfunction (acute kidney injury) occurred.
We here established a model of septic shock in pigs that meets the clinical criteria of septic shock utilized in human patients. Our model may thus serve as a reference for clinically relevant sepsis research in pigs.
脓毒症是由宿主对感染的反应失调引起的危及生命的器官功能障碍。脓毒症患者的死亡率很高，在过去几十年中基本没有变化。动物模型已被广泛用于脓毒症和脓毒性休克的研究，但转化为临床有效的治疗方案大多失败。由于猪在解剖学、遗传学和免疫系统方面与人类具有高度的可比性和相似性，因此被认为是研究人类疾病的合适模型。我们在此评估了先前报道的猪脓毒性休克模型，并建立了一种符合猪脓毒性休克临床标准的新型多微生物脓毒症模型。
使用关键词“猪”、“脓毒症”和“脓毒性休克”进行文献检索。为了在n = 10头德国长白猪中建立脓毒性休克模型，开始机械通气，建立中心静脉和动脉导管，并通过脉搏轮廓心输出量测量（PiCCO）进行有创血流动力学监测。通过向腹腔内注入3 g/kg体重的粪便诱导腹腔多微生物粪便脓毒症。根据第三次国际共识定义（脓毒症-3）定义脓毒性休克。休克发生后，猪接受了为期1小时的人类脓毒症治疗方案。通过酶联免疫吸附测定法测量细胞因子水平。
已发表的猪脓毒症模型表现出高度的方法学变异性，不符合脓毒性休克的临床标准。在我们的模型中，脓毒性休克平均在4.8±0.29小时后发生，与血压可重复下降（平均动脉压54±1 mmHg）和明显的高乳酸血症（3.76±0.65 mmol/L）相关。脓毒性休克与白细胞介素-6（IL6）水平升高以及最初的心脏抑制有关，随后是高动力阶段，在初始复苏后全身血管阻力指数显著下降。此外，还发生了器官功能障碍（急性肾损伤）。
我们在此建立了一种符合人类患者使用的脓毒性休克临床标准的猪脓毒性休克模型。因此，我们的模型可为猪的临床相关脓毒症研究提供参考。
