ABSTRACT
I. Introduction Acute respiratory distress syndrome (ARDS) represents a devastating clinical condition for which there exist few treatment options. While great scientific strides have been made in the last decades in terms of defining molecular pathways, applicability of these discoveries to tangible treatments for human disease has been limited. A major challenge in generating effective therapeutics has been the ability to develop reliable animal models of critical illness that allow generation and testing of novel hypotheses and, ultimately, translatability of the findings to the human condition. While there exist larger animal models of critical illness, the expense and complexity of these studies have limited widespread use of these systems for basic experimentation. Murine models of ARDS are appealing for experimental design for many reasons, including the ability to rapidly breed large numbers of animals that can be carefully studied with appropriate controls and the capability of studying animals with complex genetic manipulations. However, disadvantages to the study of ARDS in mice include inherent differences in murine and human genetics and response to disease, as well as significant heterogeneity of the interaction of the human genome with a complex environment that is impossible to model. That being said, there exists a wealth of critical information that has yet to be gleaned from the study of mouse models of ARDS, and understanding of the methods of experimentation and their limitations are important for our ability to move forward with clinically relevant translational studies. The current understanding of ARDS pathophysiology and underlying mechanisms are reviewed elsewhere in detail in this book. We will therefore highlight how animal experimental studies have and can be applied toward discerning mechanisms of complex lung disease, through examining key pathophysiologic features of the development of ARDS.
