Ten Have Gabriella A M, Deutz Renske C I, Engelen Mariëlle P K J, Wolfe Robert R, Deutz Nicolaas E P
1 Center for Translational Research in Aging and Longevity, Department of Health and Kinesiology, Texas A&M University, College Station, Texas, USA.
2 Donald W Reynolds Institute on Aging, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
Lab Anim. 2018 Apr;52(2):163-175. doi: 10.1177/0023677217718003. Epub 2017 Jul 5.
Survival of sepsis is related to loss of muscle mass. Therefore, it is imperative to further define and understand the basic alterations in nutrient metabolism in order to improve targeted sepsis nutritional therapies. We developed and evaluated a controlled hyperdynamic severe sepsis pig model that can be used for in vivo multi-organ metabolic studies in a conscious state. In this catheterized pig model, bacteremia was induced intravenously with 10 CFU/h Pseudomonas aeruginosa (PA) in 13 pigs for 18 h. Both the PA and control (nine) animals received fluid resuscitation and were continuously monitored. We examined in detail their hemodynamics, blood gases, clinical chemistry, inflammation, histopathology and organ plasma flows. The systemic inflammatory response (SIRS) diagnostic scoring system was used to determine the clinical septic state. Within 6 h from the start of PA infusion, a septic state developed, as was reflected by hyperthermia and cardiovascular changes. After 12 h of PA infusion, severe sepsis was diagnosed. Disturbed cardiovascular function, decreased portal drained viscera plasma flow (control: 37.6 ± 4.6 mL/kg body weight (bw)/min; PA 20.3 ± 2.6 mL/kg bw/min, P < 0.001), as well as moderate villous injury in the small intestines were observed. No lung, kidney or liver failure was observed. Acute phase C-reactive protein (CRP) and interleukin-6 (IL-6) levels did not change in the PA group. However, significant metabolic changes such as enhanced protein breakdown, hypocalcemia and hypocholesterolemia were found. In conclusion, PA-induced bacteremia in a catheterized pig is a clinically relevant model for acute severe sepsis and enables the study of complex multi-organ metabolisms.
脓毒症的存活与肌肉量的减少有关。因此，进一步明确和了解营养代谢的基本改变对于改善脓毒症的靶向营养治疗至关重要。我们开发并评估了一种可控的高动力性严重脓毒症猪模型，该模型可用于清醒状态下的体内多器官代谢研究。在这个插管猪模型中，13头猪通过静脉注射每小时10 CFU的铜绿假单胞菌（PA）诱导菌血症，持续18小时。PA组和对照组（9头）动物均接受液体复苏并持续监测。我们详细检查了它们的血流动力学、血气、临床化学、炎症、组织病理学和器官血浆流量。采用全身炎症反应（SIRS）诊断评分系统来确定临床脓毒症状态。从PA输注开始后6小时内，出现了脓毒症状态，表现为体温升高和心血管变化。PA输注12小时后，诊断为严重脓毒症。观察到心血管功能紊乱、门静脉引流内脏血浆流量减少（对照组：37.6±4.6 mL/kg体重（bw）/分钟；PA组：20.3±2.6 mL/kg bw/分钟，P<0.001），以及小肠中度绒毛损伤。未观察到肺、肾或肝功能衰竭。PA组急性期C反应蛋白（CRP）和白细胞介素-6（IL-6）水平未发生变化。然而，发现了显著的代谢变化，如蛋白质分解增强、低钙血症和低胆固醇血症。总之，插管猪中PA诱导的菌血症是急性严重脓毒症的一个临床相关模型，能够用于研究复杂的多器官代谢。
