Skip to main content
SpringerLink
Log in

Physiological and chemical indicators for early and late stages of sepsis in conscious rats

  • Original Paper
  • Published:
Journal of Biomedical Science

Abstract

Endotoxin shock is a major cause of death in patients with septicemia. Endotoxin induces nitric oxide (NO) production and causes tissue damage. In addition, the release of oxygen free radicals has also been observed in endotoxin shock and was found to be responsible for the occurrence of multiple organ failure. The purpose of the present study was to evaluate suitable indicators for early and late stages of endotoxin shock. The experiments were designed to induce endotoxin shock in conscious rats by means of anEscherichia coli lipopolysaccharide (LPS) injection. Arterial pressure (AP) and heart rate (HR) were continuously monitored for 72 h after LPS administration. The maximal decrease in AP and increase in HR and nitrate/nitrite level occurred at 9–12 h following LPS administration. The white blood cell (WBC) count had decreased at 3 h. Hydroxyl radical (methyl guanidine, MG) decreased rapidly after LPS administration. Plasma levels of blood urea nitrogen (BUN), creatinine (Cr), lactic dehydrogenase (LDH), creatine phosphokinase (CPK), and glutamic oxaloacetic transaminase increased before the rise of amylase. Our results suggest that changes in AP, HR, WBC, free radicals, and chemical substances (BUN, Cr) can possibly serve as approximate indicators for the early stage of endotoxin shock. Severe multiple organ damage may be caused by amylase release in the late stage of endotoxin shock.

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

Similar content being viewed by others

References

  1. Ayala A, Evans TA, Chaudry IH. Does hepatocellular injury in sepsis involve apoptosis? J Surg Res 76:165–173;1998.

    Article  PubMed  Google Scholar 

  2. Bernard C, Merval R, Esposito B, Tedgui A. Resistance to endotoxin shock in spontaneously hypertensive rats. Hypertension 31:1350–1356;1998.

    PubMed  Google Scholar 

  3. Chan CC, Hwang SJ, Lee FY, Wang SS, Chang FY, Li CP, Chu CJ, Lu RH, Lee SD. Prognostic value of plasma endotoxin levels in patients with cirrhosis. Scand J Gastroenterol 32:942–946;1997.

    PubMed  Google Scholar 

  4. Cowley HC, Bacon PJ, Goode HF, Webster NR, Jones JG, Menon DK. Plasma antioxidant potential in severe sepsis: a comparison of survivors and non-survivors. Crit Care Med 24:1179–1183;1996.

    Article  PubMed  Google Scholar 

  5. Goode HF, Cowley HC, Walker BE, Howdle PD, Webster NR. Decreased antioxidant status and increased lipid peroxidation in patients with septic shock and secondary organ dysfunction. Crit Care Med 23:646–651;1995.

    Article  PubMed  Google Scholar 

  6. Goode HF, Webster NR. Free radical and antioxidant in sepsis. Crit Care Med 21:1770–1776;1993.

    PubMed  Google Scholar 

  7. Lee RP, Wang D, Kao SJ, Chen HI. The lung is the major site that produces nitric oxide to induce acute pulmonary edema in endotoxin shock. Clin Exp Pharmacol Physiol 28:315–320;2001.

    Article  PubMed  Google Scholar 

  8. Lee RP, Wang D, Lin NT, Chen HI. A modified technique for tail-cuff pressure measurement in unrestrained rats at conscious state. J Biomed Sci 9:424–427;2002.

    Google Scholar 

  9. Leff JA, Parsons PE, Day CE. Serum antioxidants as predictors of adult respiratory distress syndrome in patients with sepsis. Lancet 341:777–780;1993.

    Article  PubMed  Google Scholar 

  10. Liu S, Adcock IM, Old RW, Barnes PJ, Evans TW. Lipopolysaccharide treatment in vivo induces widespread tissue expression of inducible nitric oxide synthase mRNA. Biochem Biophys Res Commun 196:1208–1213;1993.

    Article  PubMed  Google Scholar 

  11. Lorente JA, Landin L, Pablo RD, Renes E, Liste D.L-Arginine pathway in the sepsis syndrome. Crit Care Med 21:1287–1295;1993.

    PubMed  Google Scholar 

  12. Maier S, Emmanuilidis K, Entleutner M, Zantl N, Werner M, Pfeffer K, Heidecke CD. Massive chemokine transcription in acute renal failure due to polymicrobial sepsis. Shock 14:187–192;2000.

    PubMed  Google Scholar 

  13. Moncada S, Palmer RM, Higgs EA. Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142;1991.

    PubMed  Google Scholar 

  14. Munford RS. Sepsis and septic shock. In: Wilson, JD, Braunwald E, Isselbacher KJ, eds. Harrison's Principles of Internal Medicine. New York, McGraw-Hill, 776–780;1997.

    Google Scholar 

  15. Muscare MN, Nucci G. Simultaneous determination of nitrite and nitrate anions in plasma, urine and cell culture supernatants by high-performance liquid chromatography with post-column reactions. J Chromatogr Biomed Appl 686:157–164;1996.

    Article  Google Scholar 

  16. Nakamura K, Ienaga K, Yokozawa T, Fujitsuka N, Oura H. Production of methyl guanidine from creatinine via cretol by active oxygen species: Analysis of the catabolism in vitro. Nephron 58:42–46;1991.

    PubMed  Google Scholar 

  17. Nakatani Y, Fukui H, Kitano H, Nagamoto I, Tsujimoto T, Kuriyama S, Kikuchi E, Hoppou K, Tsujii T. Endotoxin clearance and its relation to hepatic and renal disturbances in rats with liver cirrhosis. Liver 21:64–70;2001.

    PubMed  Google Scholar 

  18. Nussler AK, Silvio MD, Billiar TR, Hoffman RA, Geller DA, Selby R, Madariaga J, Simmons L. Stimulation of the nitric oxide synthase pathway in human hepatocytes by cytokines by cytokines and endotoxin. J Exp Med 176:261–264;1992.

    Article  PubMed  Google Scholar 

  19. Pagana KD. Diagnostic and Laboratory Test Reference. London, Mosby-Year Book Inc., 51–838;1997.

    Google Scholar 

  20. Parrillo JE. Pathogenetic mechanisms of septic shock. N Engl J Med 328:1471–1477;1993.

    Article  PubMed  Google Scholar 

  21. Peake SL, Moran JL, Leppard PI. N-acetyl-L-cysteine depresses cardiac performance in patients in septic shock. Crit Care Med 24:1302–1310;1996.

    Article  PubMed  Google Scholar 

  22. Pozsar J, Schwab R, Simon K, Fekete L, Orgovan G, Pap A. Effect of endotoxin administration on the severity of acute pancreatitis in two experimental models. Int J Pancreas 22:31–37;1997.

    Google Scholar 

  23. Robbins RA, Springall DR, Warren JB, Kwon OJ, Buttery LD, Wilson AJ, Adconck IM, Riveros-Moreno V, Moncada S, Polak J, Barnes PJ. Inducible nitric oxide synthase is increased in murine lung epithelial cells by cytokine stimulation. Biochem Biophys Res Commun 198:835–843;1994.

    Article  PubMed  Google Scholar 

  24. Salzman AL, Menconi MJ, Unno N, Ezzel RM, Casey DM, Gonzalez PK, Fink MP. Nitric oxide dilates tight junctions and depletes ATP in culture Caco-2BB intestinal epithelial monolayers. Am J Physiol 268:G361-G373;1995.

    PubMed  Google Scholar 

  25. Schmid-Schonbein GW, Seiffge D, DeLaano FA, Shen K, Zweichach BW. Leukocyte counts and activation in spontaneously hypertensive and normotensive rats. Hypertension 17:323–330;1991.

    PubMed  Google Scholar 

  26. Stamler JS, Loh E, Roddy MA, Currie KE, Creager MA. Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans. Circulation 89:2035–2040;1994.

    PubMed  Google Scholar 

  27. Stewart TE, Valenza F, Ribeiro SP. Increased nitric oxide in exhaled gas as an early marker of lung inflammation in a model of sepsis. Am J Respir Crit Care Med 151:713–718;1995.

    PubMed  Google Scholar 

  28. Szabo C, Cuzzocrea B, Zingarelli B, O'Connor B, Salzman L. Endothelium dysfunction in a rat model of endotoxic shock: Importance of the activation of poly (ADP-ribose) synthetase by peroxynitrite. J Clin Invest 100:723–735;1997.

    PubMed  Google Scholar 

  29. Szabo C, Mitchell JA, Thiemermann C, Vane JR. Nitric oxide mediated hyporeactivity to noradrenaline precedes the induction of nitric oxide synthase in endotoxin shock. Br J Pharmacol 108:786–792;1993.

    PubMed  Google Scholar 

  30. Vaccaro MI, Dagrosa MA, Mora MI, Tiscornia OM, Sordelli DO. The effect of chronic intraperitoneal infusion of bacterial endotoxin on exocrine pancreas function in rats. Int J Pancreas 19:49–54;1996.

    Google Scholar 

  31. Wang D, Wei J, Hsu K, Chao DE, Chen HI. Effects of nitric oxide synthase (NOS) inhibitors on the systemic hypotension, cytokines and inducible NOS expression and lung injury following endotoxin in rats. J Biomed Sci 6:28–35;1999.

    Google Scholar 

  32. Wright CE, Rees DD, Moncada S. Protective and pathological roles of nitric oxide in endotoxin shock. Cardiovasc Res 26:48–57;1992.

    PubMed  Google Scholar 

  33. Zapol WM, Rimar S, Gillis N, Marletta M, Bosken CH. Nitric oxide and the lung. Am J Respir Crit Care Med 149:1375–1380;1994.

    PubMed  Google Scholar 

  34. Zurovsky Y, Haber C. Antioxidants attenuate endotoxin-gentamicin induced acute renal failure in rats. Scand J Urol Nephrol 29:147–154;1995.

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nursing, Cheng Hsin General Hospital, Taiwan

    Ru Ping Lee

  2. Department of Nursing, Tzu Chi College of Technology, Cheng Hsin General Hospital, Taiwan

    David Wang

  3. Department of Microbiology, Tzu Chi University, Hualien, Taiwan

    Nien Tsung Lin

  4. Department of Physiology, Tzu Chi University, Hualien, Taiwan

    Hsing I. Chen MD, PhD

  5. Institute of Medical Sciences, Tzu Chi University, No. 701, Chung Yan Rd., Sec. 3, 97004, Hualien, Taiwan (ROC)

    Ru Ping Lee &  Hsing I. Chen MD, PhD

Authors
  1. Ru Ping Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. David Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Nien Tsung Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hsing I. Chen MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, R.P., Wang, D., Lin, N.T. et al. Physiological and chemical indicators for early and late stages of sepsis in conscious rats. J Biomed Sci 9, 613–621 (2002). https://doi.org/10.1007/BF02254989

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02254989

Key Words

Search

Navigation