Establishment of the critical period of severe acute pancreatitis-associated lung injury.
BACKGROUND
Since respiratory dysfunction is the main cause of death in patients with severe acute pancreatitis (SAP), elucidating the critical period of acute pancreatitis-associated lung injury (APALI) is of important clinical value. This study aimed to define the risk period of APALI by a series of studies including a dynamic analysis of total water content, ultrastructure and number of type II alveolar epithelial cells, and reactive oxygen metabolites (ROMs) of lung tissue in a mouse model of SAP, and a clinical analysis of APALI patients.


METHODS
ICR mice were selected to establish a SAP model. They were given 7 intraperitoneal injections of cerulein (50 microg/kg body weight) at hourly intervals, followed by an intraperitoneal injection of lipopolysaccharide (15 mg/kg body weight). The total water content, ultrastructure, and number of type II alveolar epithelial cells, and ROMs of lung tissue were assessed before (0 hour) and after the establishment of SAP model (6 hours, 12 hours, 1 day, 4 days, and 7 days). In addition, we analyzed the data from 215 patients with APALI (PaO(2) <60 mmHg) treated at our hospital between January 1998 and December 2006. Statistical analyses were made using the F test. P values less than 0.05 were regarded as statistically significant.


RESULTS
The total water content and ultrastructure of type II alveolar epithelial cells (mitochondria and lamellar bodies) of the lung in the SAP mice were significantly altered at 12 hours after the establishment of SAP model, and reached a maximum at 1 to 4 days. The number of type II alveolar epithelial cells and ROMs increased maximally at 1 day after the establishment of the model. Furthermore, clinical results showed that lung injury occurred at a mean of 3.1435+/-1.0199 days in patients with SAP. These clinical data were almost consistent with the results of the SAP model.


CONCLUSIONS
The risk period for APALI is between the first and fourth day during the course of SAP.
Chen
Yi-Peng
YP
Department of Gastroenterology, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China. yipeng_chen@sina.com.cn.
Ning
Jian-Wen
JW
Ji
Feng
F
D055371:Acute Lung Injury / Q000453:epidemiology* / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D002108:Ceruletide / Q000009:adverse effects; D004195:Disease Models, Animal; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D008070:Lipopolysaccharides / Q000009:adverse effects; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D010195:Pancreatitis / Q000139:chemically induced / Q000150:complications*; D011650:Pulmonary Alveoli / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D017382:Reactive Oxygen Species / Q000378:metabolism; D012307:Risk Factors; D013997:Time Factors; D014867:Water / Q000378:metabolism
D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D014867:Water; D008315:Malondialdehyde; D002108:Ceruletide