Experimental models of sepsis and septic shock: an overview

Abstract

Sepsis remains a major cause of morbidity and mortality in surgical patients and trauma victims, mainly due to sepsis-induced multiple organ dysfunction. In contrast to preclinical studies, most clinical trials of promising new treatment strategies for sepsis have fails to demonstrate efficacy. Although many reasons could account for this discrepancy, the misinterpretation of preclinical data obtained from experimental studies, and especially the use of animal models that do not adequately mimic human sepsis may have been contributing factors. In this review, the benefits and limitations of various animal models of sepsis are discussed to clarify the extend to which findings are relevant to human sepsis, particularly with respect to the subsequent design and execution of clinical trials. Such models include intravascular infusion of endotoxin or live bacteria, bacterial peritonitis, cecal ligation and perforation, soft tissue infection, pneumonia or meningitis models, using different animal species including rats, mice, rabbits, dogs, pigs, sheep and nonhuman primates. Despite several limitations, animal models remain essential in the development of all new therapies for sepsis and septic shock, because they provide fundamental information about the pharmacokinetics, toxicity, and mechanism of drug action that cannot be duplicated by other methods. New therapeutic agents should be studies in infection models, even after the initiation of the septic process. Furthermore, debility conditions need to be reproduced to avoid the exclusive use of healthy animals, which often do not represent the human septic patient.

Uso de animais em cirurgia experimental

“…Apesar de simples não há como se prever o impacto da agressão séptica. A evolução para o óbito se instala de forma muito mais precoce nos animais de laboratório do que aquela observada na espécie humana 31,32 . Ratos com freqüência são selecionados para o uso em pesquisas que abordam aspectos nutricionais, choque, sepse, câncer e cicatrização Os coelhos são muito aproveitados em estudos oftalmológicos, de plástica ou de cirurgia vascular.…”

Histological features of peritoneal lavage with ropivacaine in rats with fecal peritonitis

“…Such a response is characterized by the activation of several systems, including complement, coagulation, kinins and fibrinolysis, cells (endothelial, leucocytes, monocytes, macrophages and mastocytes), and the release of mediators (free oxygen radicals, histamine, eicosanoids, coagulation factors, and cytokines) 2,3 .…”

Median lethal needle caliber in two models of experimental sepsis

“…The advantage of puncturing the cecum is to create a more predictable onset than waiting for spontaneous rupture of the residual cecum 14 .…”

“…Three general models are usually employed to produce experimental sepsis 14 The most utilized model in pre-clinical studies is cecal ligation and puncture because it reflects the complexity of human sepsis 15 . This model satisfies many criteria essential for an experimental model.…”