Does animal model on ventilator-associated pneumonia reflect physiopathology of sepsis mechanisms in humans?

Abstract

Ventilator-associated pneumonia (VAP) is the leading cause of death in critically ill patients in intensive care units. In the last 20 years, different animal models have been a valuable tool for the study of pathophysiology and phenotypic characteristics of different lung infections observed in humans, becoming an essential link between ''in vitro'' testing and clinical studies. Different animal models have been used to study the mechanism of a deregulated inflammatory response and host tissue damage of sepsis in VAP, as well as different infection parameters such as clinical, physiological, microbiological and pathological facts in several large and small mammals. In addition, the dosage of inflammatory modulators and their consequences in local and systemic inflammation, or even the administration of antibiotics, have been evaluated with very interesting results. Although some bronchial inoculation ways do not resemble the common pathophysiologic mechanisms, the experimental model of VAP induced by the inoculation of high concentrations of pathogens in mechanically ventilated animals is useful for studying the local and systemic responses of sepsis in VAP and it reproduces biological mechanisms such as acute lung injury, distress response, cardiac events and immune modulation comparable with clinical studies.

Keywords: Animal model; antimicrobial therapy; inflammatory markers; sepsis mechanisms; ventilator-associated pneumonia (VAP).

Figure 1

Temperature, PaO₂/FiO₂, airway pressures and compliance variations in piglets. (A) (a) After inoculation the temperature rose steeply, being 36.6±1.0 °C, at baseline and rising to 39.4±1.4 °C at 24 hours (*), P=0.0002 and 38.1±1.8 °C at 48 hours (*), P=0.021. (b) body temperature tended to be higher in piglets not receiving ABT, beginning 24 hours after inoculation. This difference became significant at the last measurement before death or sacrifice (*) P=0.018. (B) PaO₂/FiO₂ decreased over time, becoming significant 24 hours after inoculation, basal =386 and at 24 hours =242 mmHg (*), P=0.034. (C) Peak and plateau pressures and compliance in the overall population at the different time points from the time of inoculation to the time of sacrifice. A continuous increase in airway pressures was obvious from the beginning of the experiment achieving significance at 2 hours, P=0.003 for peak (*) and P=0.007 for plateau (§) pressures. Static compliance reduction became significant at 72 hours (ǂ), P=0.009. These changes may be attributed to pneumonia and to acute lung injury. According with Luna et al. (25).

Figure 2

Confluent pneumonia. Micro-photograph showing alveolar spaces with polymorphonuclear leukocytes infiltration. It also shows the alveolar epithelium covered by hyaline membranes. Hematoxylin-eosin 250×. According with Luna et al. (25).

Figure 3

Abscess pneumonia. Consolidation; infiltration of polymorphonuclear leukocytes, fibrinous exudates, and cellular necrosis with disruption of cellular architecture. Hematoxylin-eosin 250×. According with Luna et al. (25).