Evaluation of lung injury and respiratory mechanics in a rat model of acute pancreatitis complicated with endotoxin

Background: Acute lung injury (ALI) is a common complication of acute pancreatitis (AP) and contributes to the majority of AP-associated deaths, particularly in the setting of secondary infection. This 'two-hit' model mimics clinical cases where the presentation of AP is associated with mild lung injury that, following a secondary direct lung infection, can result in respiratory dysfunction and death.We therefore aimed to characterize lung injury in a clinically-relevant 'two-hit' rat model of caerulein-induced AP combined with intratracheal endotoxin. Methods: Rats received 7 hourly intraperitoneal injections of caerulein (50 mg/kg). Twenty four hours following the first caerulein injection, rats were anaesthetised and LPS (15 mg/kg) was instilled intratracheally. Following LPS instillation, rats were ventilated for a total of 2 h. Results: In the present study, AP results in mild pulmonary injury indicated by increased lung myeloperoxidase (MPO) activity and edema, but with no alteration of respiratory function, while intratracheal instillation of LPS results in more substantial pulmonary injury. The induction of AP challenged with secondary intratracheal LPS results in an exacerbation of lung damage indicated by further increased lung edema, plasma and bronchoalveolar (BAL) CINC-1 concentration, lung damage histology score, and lung tissue resistance and elastance, compared with LPS alone. Conclusions: In conclusion, the addition of instilled LPS acted as a "second-hit" and exacerbated caerulein-induced AP, compared with the induction of AP alone or the instillation of LPS alone. Given its clinical relevance, this model could prove useful for examination of therapeutic interventions for ALI following secondary infection.