Animal models of ventilator-associated pneumonia

Abstract

Animal models are an essential step between "in vitro" testing and clinical studies. Different animal models have been useful for the study of pathophysiology, diagnosis and therapy in ventilator-associated pneumonia (VAP). Aspiration has been studied in dog and cat models and bacteriological diagnosis has been evaluated in baboons. Pigs have been used for studying either spontaneous or induced VAP. Intubated piglets in prone position were administered analgesia and muscle paralysis was induced, and the intubated piglets underwent mechanical ventilation for several days. In this model, spontaneous VAP due to common bacterial pig colonisation develops within a few days. Pneumonia can also be induced by inoculating high concentrations of microorganisms (Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus). Different clinical, physiological, microbiological and pathological parameters of infection have been studied in this model. In addition, administration of antibiotics and inflammatory modulators and their consequences in microbiological eradication and local and systemic inflammation have been evaluated with interesting translational results. Although bronchial inoculation of healthy subjects does not resemble the common pathophysiological mechanisms, the experimental model of ventilator-associated pneumonia induced by the inoculation of high concentrations of microorganisms in mechanically ventilated piglets is useful for the study of the local and systemic responses of lung infection and for the determination of potential measures of prevention or therapeutic modulation.