What have we learned from animal models of ventilator-induced lung injury?
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What have we learned from animal models of ventilator‑induced lung injury? Patricia Rieken Macedo Rocco1* and John J. Marini2 © 2020 Springer-Verlag GmbH Germany, part of Springer Nature
Despite its obvious benefits, mechanical ventilation can inflict pulmonary structural damage [1] and destabilize hemodynamics [2]. Deleterious effects of mechanical ventilation—collectively known as ventilator-induced lung injury (VILI)—include inflammatory infiltration and vascular permeability, hyaline membrane formation, and pulmonary edema [3]. Interactive mechanical forces prompt biophysical, biochemical, and biomolecular alterations that ultimately lead to VILI [4]. Repeated nonphysiological stretching of lung tissue can release inflammatory mediators, alter gene expression, and either upregulate or downregulate synthesis of several extracellular matrix proteins [5]. Therefore, understanding the physiological and biological consequences of mechanical ventilation and becoming familiar with logical clinical strategies intended to prevent and minimize lung damage are important clinical goals. These cannot be studied directly at the bedside for obvious ethical and logistical reasons. Yet, over the past two decades, the experimental laboratory has provided the needed guidance to develop approaches and equipment modifications essential to VILI prevention. Animal models continue to elucidate mechanisms underlying the complex pathophysiology of VILI, aiding immeasurably in developing preventative and therapeutic approaches. Important factors upon which to focus when selecting an animal model of VILI include availability, cost, public opinion regarding the conduct of animal research (e.g., feelings toward dogs or primates compared to rodents), the number of animals that should be used, *Correspondence: [email protected] 1 Laboratory of Pulmonary Investigation, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro Centro de Ciências da Saúde, Av. Carlos Chagas Filho, 373, Bloco G‑014, Ilha do Fundão, Rio de Janeiro, RJ 21941‑902, Brazil Full author information is available at the end of the article
and the availability of species-specific reagents to measure inflammatory mediators, receptors, or other proteins [6]. Different species are best suited to different study objectives; if survival is the primary outcome of interest, rodents provide an ideal option, since large numbers are required. Mouse models of injury have specific reagents available and can be genetically modified. Conversely, if invasive monitoring or multiple blood samples are required, large animals share similarities of chest anatomy and mechanical properties with humans and provide easier anatomic access and adequate blood volumes. So far, no available animal model perfectly mimics certain key aspects of human VILI, limiting the breadth of our understanding and impeding rapid extrapolation of findings to the clinical setting. For example, the intensity and evolution of VILI differ between experimental and
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