Skip to main content
SpringerLink
Log in

Hemorrhage-Induced Hepatic Injury and Hypoperfusion can be Prevented by Direct Peritoneal Resuscitation

  • 2008 ssat poster presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Background

Crystalloid fluid resuscitation after hemorrhagic shock (HS) that restores/maintains central hemodynamics often culminates in multi-system organ failure and death due to persistent/progressive splanchnic hypoperfusion and end-organ damage. Adjunctive direct peritoneal resuscitation (DPR) using peritoneal dialysis solution reverses HS-induced splanchnic hypoperfusion and improves survival. We examined HS-mediated hepatic perfusion (galactose clearance), tissue injury (histopathology), and dysfunction (liver enzymes).

Methods

Anesthetized rats were randomly assigned (n = 8/group): (1) sham (no HS); (2) HS (40% mean arterial pressure for 60 min) plus conventional i.v. fluid resuscitation (CR; shed blood + 2 volumes saline); (3) HS + CR + 30 mL intraperitoneal (IP) DPR; or (4) HS + CR + 30 mL IP saline. Hemodynamics and hepatic blood flow were measured for 2 h after CR completion. In duplicate animals, liver and splanchnic tissues were harvested for histopathology (blinded, graded), hepatocellular function (liver enzymes), and tissue edema (wet–dry ratio).

Results

Group 2 decreased liver blood flow, caused liver injuries (focal to submassive necrosis, zones 2 and 3) and tissue edema, and elevated liver enzymes (alanine aminotransferase (ALT), 149 ± 28 μg/mL and aspartate aminotransferase (AST), 234 ± 24 μg/mL; p < 0.05) compared to group 1 (73 ± 9 and 119 ± 10 μg/mL, respectively). Minimal/no injuries were observed in group 3; enzymes were normalized (ALT 89 ± 9 μg/mL and AST 150 ± 17 μg/mL), and tissue edema was similar to sham.

Conclusions

CR from HS restored and maintained central hemodynamics but did not restore or maintain liver perfusion and was associated with significant hepatocellular injury and dysfunction. DPR added to conventional resuscitation (blood and crystalloid) restored and maintained liver perfusion, prevented hepatocellular injury and edema, and preserved liver function.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Hassoun HT, Kone BC, Mercer DW, Moody FG, Weisbrodt NW, Moore FA. Post-injury multiple organ failure: the role of the gut. Shock 2001;15:1–10.

    Article  PubMed  CAS  Google Scholar 

  2. Fruchterman TM, Spain DA, Wilson MA, Harris PD, Garrison RN. Selective microvascular endothelial cell dysfunction in the small intestine following resuscitated hemorrhagic shock. Shock 1998;10:417–422. doi:10.1097/00024382-199812000-00007.

    Article  PubMed  CAS  Google Scholar 

  3. Wang P, Hauptman JG, Chaudry IH. Hemorrhage produces depression in microvascular blood flow which persists despite fluid resuscitation. Circ Shock 1990;32:307–318.

    PubMed  CAS  Google Scholar 

  4. Zakaria ER, Spain DA, Harris PD, Garrison RN. Resuscitation regimens for hemorrhagic shock must contain blood. Shock 2002;18:567–573. doi:10.1097/00024382-200212000-00014.

    Article  Google Scholar 

  5. Deitch EA, Xu D, Franko L, Ayala A, Chaudry IH. Evidence favoring the role of the gut as a cytokine-generating organ in rats subjected to hemorrhagic shock. Shock 1994;1:141–145.

    Article  PubMed  CAS  Google Scholar 

  6. Wang P, Hauptman JG, Chaudry IH. Hepatocellular dysfunction occurs early after hemorrhage and persists despite fluid resuscitation. J Surg Res 1990;48:464–470.

    Article  PubMed  CAS  Google Scholar 

  7. Wang P, Ba ZF, Chaudry IH. Endothelial cell dysfunction occurs very early following trauma-hemorrhage and persists despite fluid resuscitation. Am J Physiol 1993;265:H973–H979.

    PubMed  CAS  Google Scholar 

  8. Zakaria ER, Garrison RN, Spain DA, Harris PD. Impairment of endothelium-dependent dilation response after resuscitation from hemorrhagic shock involved postreceptor mechanisms. Shock 2004;21:175–181. doi:10.1097/00024382-200402000-00014.

    Article  Google Scholar 

  9. Zweifach BW. Mechanisms of blood flow and fluid exchange in microvessels: hemorrhagic hypotension model. Anesthesiology 1974;41:157–168. doi:10.1097/00000542-197408000-00006.

    Article  PubMed  CAS  Google Scholar 

  10. Zakaria ER, Garrison RN, Spain DA, Matheson PJ, Harris PD, Richardson JD. Intraperitoneal resuscitation improves intestinal blood flow following hemorrhagic shock. Ann Surg 2003;237:704–711. doi:10.1097/00000658-200305000-00013.

    Article  Google Scholar 

  11. Zakaria ER, Garrison RN, Kawabe T, Harris PD. Direct peritoneal resuscitation from hemorrhagic shock: effect of time delay in therapy initiation. J Trauma 2005;58:499–506. doi:10.1097/01.TA.0000152892.24841.54.

    Article  Google Scholar 

  12. Garrison RN, Conn AA, Harris PD, Zakaria ER. Direct peritoneal resuscitation as adjunct to conventional resuscitation from hemorrhagic shock: a better outcome. Surgery 2004;136:900–908. doi:10.1016/j.surg.2004.06.027.

    Article  PubMed  Google Scholar 

  13. Zakaria ER, Hurt RT, Matheson PJ, Garrison RN. A novel method of peritoneal resuscitation improves organ perfusion after hemorrhagic shock. Am J Surg 2003;186:443–448. doi:10.1016/j.amjsurg.2003.07.006.

    Article  Google Scholar 

  14. Chojkier M, Fierer J. d-Galactosamine hepatotoxicity is associated with endotoxin sensitivity and mediated by lymphoreticular cells in mice. Gastroenterology 1985;88:115–121.

    PubMed  CAS  Google Scholar 

  15. Shiratori Y, Kawase T, Shiina S, Okano K, Sugimoto T, Teraoka H, Matano S, Matsumoto K, Kamii K. Modulation of hepatotoxicity by macrophages in the liver. Hepatology 1988;8:815–821. doi:10.1002/hep.1840080420.

    Article  PubMed  CAS  Google Scholar 

  16. Wang P, Ba ZF, Biondo A, Chaudry I. Liver endothelial cell dysfunction occurs early following hemorrhagic shock and persists despite crystalloid resuscitation. J Surg Res 1996;63:241–247. doi:10.1006/jsre.1996.0255.

    Article  PubMed  CAS  Google Scholar 

  17. Bauer M, Marzi I, Ziegenfuss T, Seeck G, Buhren V, Larsen R. Comparative effects of crystalloid and small volume hypertonic hyperoncotic fluid resuscitation on hepatic microcirculation after hemorrhagic shock. Circ Shock 1993;40:187–193.

    PubMed  CAS  Google Scholar 

  18. Corso CO, Okamoto S, Leiderer R, Messmer K. Resuscitation with hypertonic saline dextran reduces endothelial cell swelling and improves hepatic microvascular perfusion and function after hemorrhagic shock. J Surg Res 1998;80:210–220. doi:10.1006/jsre.1998.5426.

    Article  PubMed  CAS  Google Scholar 

  19. Dart RC, Liebler DC, Sipes IG. Hepatic injury and lipid peroxidation during hemorrhagic shock and resuscitation. Life Sci 1993;53:1685–1690. doi:10.1016/0024-3205(93)90205-H.

    Article  PubMed  CAS  Google Scholar 

  20. Holliday RL, Illner HP, Shires GT. Liver cell membrane alterations during hemorrhagic shock in the rat. J Surg Res 1981;31:506–515. doi:10.1016/0022-4804(81)90189-X.

    Article  PubMed  CAS  Google Scholar 

  21. Jarrar D, Wang P, Cioffi WG, Bland KI, Chaudry IH. Critical role of oxygen radicals in the initiation of hepatic depression after trauma hemorrhage. J Trauma 2000;49:879–885. doi:10.1097/00005373-200011000-00015.

    Article  PubMed  CAS  Google Scholar 

  22. Flynn WJ, Cryer HG, Garrison RN. Pentoxifylline restores intestinal microvascular blood flow during resuscitated hemorrhagic shock. Surgery 1991;110:350–356.

    PubMed  CAS  Google Scholar 

  23. Flynn WJ, Cryer HG, Garrison RN. Pentoxifylline but not saralasin restores hepatic blood flow after resuscitation from hemorrhagic shock. J Surg Res 1991;50:616–621. doi:10.1016/0022-4804(91)90051-M.

    Article  PubMed  CAS  Google Scholar 

  24. Fruchterman TM, Spain DA, Wilson MA, Harris PD, Garrison RN. Selective microvascular endothelial cell dysfunction in the small intestine following resuscitated hemorrhagic shock. Shock 1998;10:417–422. doi:10.1097/00024382-199812000-00007.

    Article  PubMed  CAS  Google Scholar 

  25. Wang P, Hauptman JG, Chaudry IH. Hemorrhage produces depression in microvascular blood flow which persists despite fluid resuscitation. Circ Shock 1990;32:307–318.

    PubMed  CAS  Google Scholar 

  26. Zakaria ER, Spain DA, Harris PD, Garrison RN. Resuscitation regimens for hemorrhagic shock must contain blood. Shock 2002;18:567–573. doi:10.1097/00024382-200212000-00014.

    Article  Google Scholar 

  27. Flynn WJ Jr, Gosche JR, Garrison RN. Intestinal blood flow is restored with glutamine or glucose suffusion after hemorrhage. J Surg Res 1992;52:499–504. doi:10.1016/0022-4804(92)90318-T.

    Article  PubMed  CAS  Google Scholar 

  28. Flynn WJ Jr, Pilati D, Hoover EL. Effect of allopurinol on venous endothelial dysfunction after resuscitated hemorrhagic shock. Int J Surg Investig 1999;1:11–18.

    PubMed  Google Scholar 

  29. Fruchterman TM, Spain DA, Wilson MA, Harris PD, Garrison RN. Complement inhibition prevents gut ischemia and endothelial cell dysfunction after hemorrhage/resuscitation. Surgery 1998;124:782–791. doi:10.1067/msy.1998.91489.

    Article  PubMed  CAS  Google Scholar 

  30. Wang P, Ba ZF, Chaudry IH. Endothelial cell dysfunction occurs after hemorrhage in nonheparinized but not in preheparinized models. J Surg Res 1993;54:499–506. doi:10.1006/jsre.1993.1077.

    Article  PubMed  CAS  Google Scholar 

  31. Watkins JM, Spain DA, Krysztopik RJ, Downard PJ, Wilson MA, Garrison RN. Heparan preserves intestinal perfusion after hemorrhage and resuscitation. J Surg Res 1996;66:154–158. doi:10.1006/jsre.1996.0388.

    Article  PubMed  CAS  Google Scholar 

  32. Zakaria ER, Li N, Garrison RN. Mechanisms of direct peritoneal resuscitation-mediated splanchnic hyperperfusion following hemorrhagic shock. Shock 2007;27:436–442. doi:10.1097/01.shk.0000245017.86117.4e.

    Article  CAS  Google Scholar 

  33. Zakaria ER, Li N, Matheson PJ, Garrison RN. Cellular edema regulates tissue capillary perfusion after hemorrhage resuscitation. Surgery 2007;142:487–496. doi:10.1016/j.surg.2007.08.007.

    Article  Google Scholar 

  34. Zakaria ER, Campbell JE, Peyton JC, Garrison RN. Postresuscitation tissue neutrophil infiltration is time-dependent and organ-specific. J Surg Res 2007;143:119–125. doi:10.1016/j.jss.2007.04.008.

    Article  Google Scholar 

  35. Mazzoni MC, Intaglietta M, Cragoe EJ Jr, Arfors KE. Amiloride-sensitive Na+ pathways in capillary endothelial cell swelling during hemorrhagic shock. J Appl Physiol 1992;73:1467–1473.

    PubMed  CAS  Google Scholar 

  36. Chang JX, Chen S, Ma LP, Jiang LY, Chen JW, Chang RM, Wen LQ, Wu W, Jiang ZP, Huang ZT. Functional and morphological changes of the gut barrier during the restitution process after hemorrhagic shock. World J Gastroenterol 2005;11:5485–5491.

    PubMed  Google Scholar 

  37. Jaeschke H. Mechanisms of Liver Injury. II. Mechanisms of neutrophil-induced liver cell injury during hepatic ischemia-reperfusion and other acute inflammatory conditions. Am J Physiol Gastrointest Liver Physiol 2006;290:G1083–G1088. doi:10.1152/ajpgi.00568.2005.

    Article  PubMed  CAS  Google Scholar 

  38. Chang TW. Improvement of survival from hemorrhagic shock by enterectomy in rats: finding to implicate the role of the gut for irreversibility of hemorrhagic shock. J Trauma 1997;42:223–230. doi:10.1097/00005373-199702000-00007.

    Article  PubMed  CAS  Google Scholar 

  39. Martin C, Boisson C, Haccoun M, Thomachot L, Mege JL. Patterns of cytokine evolution (tumor necrosis factor-alpha and interleukin-6) after septic shock, hemorrhagic shock, and severe trauma. Crit Care Med 1997;25:1813–1819. doi:10.1097/00003246-199711000-00018.

    Article  PubMed  CAS  Google Scholar 

  40. Matsutani T, Kang SC, Miyashita M, Sasajima K, Choudhry MA, Bland KI, Chaudry IH. Liver cytokine production and ICAM-1 expression following bone fracture, tissue trauma, and hemorrhage in middle-aged mice. Am J Physiol Gastrointest Liver Physiol 2007;292:G268–G274. doi:10.1152/ajpgi.00313.2006.

    Article  PubMed  CAS  Google Scholar 

  41. Roumen RM, Hendriks T, Van der Ven-Jongekrijg J, Nieuwenhuijzen GA, Sauerwein RW, van der Meer JW, Goris RJ. Cytokine patterns in patients after major vascular surgery, hemorrhagic shock, and severe blunt trauma. Relation with subsequent adult respiratory distress syndrome and multiple organ failure. Ann Surg 1993;218:769–776. doi:10.1097/00000658-199312000-00011.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, University of Louisville, Louisville, KY, USA

    Ryan T. Hurt

  2. Weil Cornell Medical College in Qatar, Doha, Qatar

    El Rasheid Zakaria

  3. Department of Physiology & Biophysics, University of Louisville, Louisville, KY, USA

    R. Neal Garrison

  4. Department of Surgery, University of Louisville, Louisville, KY, 40292, USA

    Paul J. Matheson & R. Neal Garrison

  5. Department of Pathology, University of Louisville, Louisville, KY, USA

    Mahoney E. Cobb & John R. Parker

  6. Louisville Veterans Affairs Medical Center, Louisville, KY, USA

    R. Neal Garrison

Authors
  1. Ryan T. Hurt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. El Rasheid Zakaria
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul J. Matheson
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mahoney E. Cobb
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John R. Parker
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. R. Neal Garrison
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R. Neal Garrison.

Additional information

No conflicts of interest exist.

Grant support: This project was supported by a VA Merit Review grant and by NIH research Grant # 5R01 HL076160-03, funded by the National Heart, Lung, and Blood Institute and the United States Army Medical Resources and Material Command.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hurt, R.T., Zakaria, E.R., Matheson, P.J. et al. Hemorrhage-Induced Hepatic Injury and Hypoperfusion can be Prevented by Direct Peritoneal Resuscitation. J Gastrointest Surg 13, 587–594 (2009). https://doi.org/10.1007/s11605-008-0796-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11605-008-0796-0

Keywords

Search

Navigation