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Intensive Care Medicine

, Volume 32, Issue 11, pp 1872–1880 | Cite as

Time course of lung injury in rat acute pancreatitis

  • Denis R. Morel
  • Jean-Louis Frossard
  • Banu Cikirikcioglu
  • Maxime Tapponnier
  • Catherine M. Pastor
Experimental

Abstract

Objective

Lung injury is a severe complication of acute pancreatitis that increases the mortality rate of the disease. The pathophysiology of acute pancreatitis has been studied in several experimental models, but the kinetics of pulmonary complications in relation to the pancreatic disease is not completely understood. We then studied the severity of acute pancreatitis-associated lung injury over 18 h in rats that had taurocholic acid injection in the pancreatic duct and determined whether blood collected from rats with pancreatitis is toxic enough to induce injury in normal lungs.

Design and setting

Prospective, randomized, and controlled animal study in an animal research laboratory in a university hospital.

Interventions

We isolated lungs from rats with acute pancreatitis 2, 6, and 18 h after taurocholic acid injection in the biliopancreatic duct and perfused them with blood collected from the same rats. Additionally, blood collected from rats with acute pancreatitis (time-points: 2 and 6 h) was perfused in normal lungs.

Measurements and results

Taurocholic acid injection induced a severe pancreatic injury that started as early as 2 h after the injection and persisted without recovery over the 18-h study period. In contrast, the pulmonary injury was transient, appearing at the 6-h time point with recovery by the end of the study. Pulmonary injury was moderate and evidenced mostly during lung reperfusion. Interestingly, blood collected at the 2-h time point in pancreatic rats induced pulmonary injury in normal lungs while blood collected at the 6-h time-point was not toxic.

Conclusions

While pancreatic injury persists over the full experimental period, pulmonary injury is transient in our experimental model. The recovery of lung injury by 18 h might be explained by a decrease in the overall toxicity of pancreatic blood over time.

Keywords

Rats Lung injury Perfused lungs Acute pancreatitis 

Notes

Acknowledgements

The authors thank Manuel Jorge-Costa, Sylvie Roulet, and Jean-Pierre Giliberto for excellent technical assistance.

Supplementary material

References

  1. 1.
    Bhatia M, Moochhala S (2004) Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol 202:145–156PubMedCrossRefGoogle Scholar
  2. 2.
    Frossard JL, Pastor CM (2002) Experimental acute pancreatitis: new insights into the pathophysiology. Front Biosci 7:275–287Google Scholar
  3. 3.
    Pastor CM, Matthay MA, Frossard JL (2003) Pancreatitis-associated lung injury. New insights. Chest 124:2341–2351PubMedCrossRefGoogle Scholar
  4. 4.
    Berry AR, Taylor TV, Davies GC (1981) Pulmonary function and fibrinogen metabolism in acute pancreatitis. Br J Surg 68:870–873PubMedGoogle Scholar
  5. 5.
    Jaffray C, Yang J, Carter G, Mendez C, Norman J (2000) Pancreatic elastase activates pulmonary nuclear factor kappa B and inhibitory kappa B, mimicking pancreatitis-associated adult respiratory distress syndrome. Surgery 128:225–231PubMedCrossRefGoogle Scholar
  6. 6.
    Hartwig W, Werner J, Jimenez RE, Z'graggen K, Weimann J, Lewandrowski KB, Warshaw AL, Fernandez-del Castillo C (1999) Trypsin and activation of circulating trypsinogen contribute to pancreatitis-associated lung injury. Am J Physiol 277:G1008–G1016PubMedGoogle Scholar
  7. 7.
    Hartwig W, Jimenez RE, Fernandez-del Castillo C, Kelliher A, Jones R, Warshaw AL (2001) Expression of the adhesion molecules Mac-1 and L-selectin on neutrophils in acute pancreatitis is protease- and complement-dependent. Ann Surg 233:371–378PubMedCrossRefGoogle Scholar
  8. 8.
    Denham W, Yang J, Norman J (1997) Evidence for an unknown component of pancreatic ascites that induces adult respiratory distress syndrome through an interleukin-1 and tumor necrosis factor-dependent mechanism. Surgery 122:295–302PubMedCrossRefGoogle Scholar
  9. 9.
    Denham W, Yang J, Wang H, Botchkina G, Tracey K, Norman J (2000) Inhibition of p38 mitogen activate kinase attenuates the severity of pancreatitis-induced adult respiratory distress syndrome. Crit Care Med 28:2567–2572PubMedCrossRefGoogle Scholar
  10. 10.
    Lampel M, Kern H (1989) Acute pancreatitis in the rat induced by excessive doses of a pancreatic secretagogue. Virchows Arch A Pathol Anat Histolpathol 373:1007–1117Google Scholar
  11. 11.
    Lombardi B, Estes L, Longnecker D (1975) Acute hemorrhagic pancreatitis (massive necrosis) with fat necrosis induced in mice by DL-ethionine fed with a choline-deficient diet. J Pathol 79:465–480PubMedGoogle Scholar
  12. 12.
    Lichtenstein A, Milani RJ, Fernezlian SM, Leme AS, Capelozzi VL, Martins MA (2000) Acute lung injury in two experimental models of acute pancreatitis: infusion of saline or sodium taurocholate into the pancreatic duct. Crit Care Med 28:1497–1502PubMedCrossRefGoogle Scholar
  13. 13.
    Pereda J, Sabater L, Cassinello N, Gomez-Cambronero L, Closa D, Folch-Puy E, Aparisi L, Calvete J, Cerda M, Lledo S, Vina J, Sastre J (2004) Effect of simultaneous inhibition of TNF-alpha production and xanthine oxidase in experimental acute pancreatitis: the role of mitogen activated protein kinases. Ann Surg 240:108–116PubMedCrossRefGoogle Scholar
  14. 14.
    Milani R, Pereiras P, Dolhnikoff M, Saldiva P, Martins M (1995) Respiratory mechanics and lung morphometry in severe pancreatitis-associated acute lung injury in rats. Crit Care Med 23:1882–1889CrossRefGoogle Scholar
  15. 15.
    Lungarella G, Gardi C, Marguetita de Santi M, Luzi P (1985) Pulmonary vascular injury in pancreatitis: evidence for a major role played by pancreatic elastase. Exp Mol Pathol 42:44–59PubMedCrossRefGoogle Scholar
  16. 16.
    Leme AS, Lichtenstein A, Arantes-Costa FM, Landucci EC, Martins MA (2002) Acute lung injury in experimental pancreatitis in rats: pulmonary protective effects of crotapotin and N-acetylcysteine. Shock 18:428–433PubMedCrossRefGoogle Scholar
  17. 17.
    Frossard JL, Hadengue A, Spahr L, Morel P, Pastor CM (2002) Natural history of long-term lung injury in mouse experimental pancreatitis. Crit Care Med 30:1541–1546PubMedCrossRefGoogle Scholar
  18. 18.
    Fujita M, Masamune A, Satoh A, Sakai Y, Satoh K, Shimosegawa T (2001) Ascites of rat experimental model of severe acute pancreatitis induces lung injury. Pancreas 22:409–418PubMedCrossRefGoogle Scholar
  19. 19.
    Dugernier TL, Laterre PF, Wittebole X, Roeseler J, Latinne D, Reynaert MS, Pugin J (2003) Compartmentalization of the inflammatory response during acute pancreatitis: correlation with local and systemic complications. Am J Respir Crit Care Med 168:148–157PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Denis R. Morel
    • 2
  • Jean-Louis Frossard
    • 3
  • Banu Cikirikcioglu
    • 2
  • Maxime Tapponnier
    • 2
  • Catherine M. Pastor
    • 1
  1. 1.Laboratoire de Physiopathologie Hépatique et Imagerie MoléculaireHôpitaux Universitaires de GenèveGenevaSwitzerland
  2. 2.Division d'Investigations AnesthésiologiquesHôpitaux Universitaires de GenèveGenevaSwitzerland
  3. 3.Division de Gastroentérologie et HépatologieHôpitaux Universitaires de GenèveGenevaSwitzerland

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