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Effects of terbutaline on circulatory failure and organ dysfunction induced by peritonitis in rats

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Abstract

Objective

The pathogenesis of multiple organ dysfunction syndrome (MODS) in septic shock is mainly caused by maldistribution of tissue perfusion and the amplification of inflammatory responses, which may be modulated by β2-adrenoceptor agonists. We evaluated and compared effects of terbutaline on MODS in a cecal ligation and puncture (CLP) model of sepsis.

Design and setting

Prospective controlled animal study in a university laboratory.

Methods

Male adult Wistar rats received CLP or sham operation followed by the administration of saline or terbutaline (0.3 mg/kg i.v. at 3 and 9 h after CLP).

Measurements and results

At 0, 9 and 18 h after CLP, the changes of hemodynamics, organ function indexes, as well as the plasma interleukin-1β (IL-1β) and nitrite/nitrate levels were examined. At 18 h after CLP, animals were killed and their lungs, livers and kidneys were immediately excised to analyze superoxide anion (O2 ) levels and inducible nitric oxide synthase (iNOS) expression. These organs were also evaluated by pathological study. Terbutaline significantly (1) prevented delayed hypotension and reduced hepatic and renal dysfunction, (2) diminished plasma IL-1β and nitrite/nitrate, lung iNOS expression, tissue O2 level and the infiltration of neutrophils in the lung and the liver, and (3) improved the 18-h survival rate.

Conclusions

Terbutaline may be developed as an alternative treatment for severe sepsis-induced MODS. The protective effect of terbutaline seems to be through inhibition of proinflammatory mediators and attenuation of oxidant production.

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References

  1. Moreno RP, Metnitz B, Adler L, Hoechtl A, Bauer P, Metnitz PG, SAPS 3 Investigators (2008) Sepsis mortality prediction based on predisposition, infection and response. Intensive Care Med 34:496–504

    Article  PubMed  Google Scholar 

  2. Matsuda N, Hattori Y (2006) Systemic inflammatory response syndrome (SIRS): molecular pathophysiology and gene therapy. J Pharmacol Sci 101:189–198

    Article  CAS  PubMed  Google Scholar 

  3. Victor VM, Rocha M, Esplugues JV, de la Fuente M (2005) Role of free radicals in sepsis: antioxidant therapy. Curr Pharm Des 11:3141–3158

    Article  CAS  PubMed  Google Scholar 

  4. Elenkov IJ, Chrousos GP, Wilder RL (2000) Neuroendocrine regulation of IL-12 and TNF-alpha/IL-10 balance: clinical implications. Ann NY Acad Sci 917:94–105

    Article  CAS  PubMed  Google Scholar 

  5. Muthu K, Deng J, Gamelli R, Shankar R, Jones SB (2005) Adrenergic modulation of cytokine release in bone marrow progenitor-derived macrophage following polymicrobial sepsis. J Neuroimmunol 158:50–57

    Article  CAS  PubMed  Google Scholar 

  6. Straub RH, Linde HJ, Mannel DN, Scholmerich J, Falk W (2000) A bacteria-induced switch of sympathetic effector mechanisms augments local inhibition of TNF-alpha and IL-6 secretion in the spleen. FASEB J 14:1380–1388

    Article  CAS  PubMed  Google Scholar 

  7. Kambalapalli M, Nichani S, Upadhyayula S (2005) Safety of intravenous terbutaline in acute severe asthma: a retrospective study. Acta Paediatr 94:1214–1217

    Article  PubMed  Google Scholar 

  8. Wu JY, Liaw WJ, Tzao C, Chen SJ, Wang JH, Wu CC (2002) Comparison of terbutaline and dobutamine in rats with endotoxemia. Chin J Physiol 45:155–162

    CAS  PubMed  Google Scholar 

  9. Liaw WJ, Tzao C, Wu JY, Chen SJ, Wang JH, Wu CC (2003) Inhibition by terbutaline of nitric oxide and superoxide anion levels of endotoxin-induced organs injury in the anesthetized rat. Shock 19:281–288

    Article  CAS  PubMed  Google Scholar 

  10. Liaw WJ, Chen TH, Lai ZZ, Chen SJ, Chen A, Tzao C, Wu JY, Wu CC (2005) Effects of a membrane-permeable radical scavenger, Tempol, on intraperitoneal sepsis-induced organ injury in rats. Shock 23:88–96

    Article  CAS  PubMed  Google Scholar 

  11. Tsao CM, Ho ST, Chen A, Wang JJ, Li CY, Tsai SK, Wu CC (2004) Low-dose dexamethasone ameliorates circulatory failure and renal dysfunction in conscious rats with endotoxemia. Shock 21:484–491

    Article  CAS  PubMed  Google Scholar 

  12. Uzuki M, Yamakage M, Fujimura N, Namiki A (2007) Direct inotropic effect of the beta-2 receptor agonist terbutaline on impaired diaphragmatic contractility in septic rats. Heart Lung 36:140–147

    Article  PubMed  Google Scholar 

  13. Monastra G, Secchi EF (1993) Beta-adrenergic receptors mediate in vivo the adrenaline inhibition of lipopolysaccharide-induced tumor necrosis factor release. Immunol Lett 38:127–130

    Article  CAS  PubMed  Google Scholar 

  14. van der Poll T, Calvano SE, Kumar A, Coyle SM, Lowry SF (1997) Epinephrine attenuates down-regulation of monocyte tumor necrosis factor receptors during human endotoxemia. J Leukoc Biol 61:156–160

    PubMed  Google Scholar 

  15. Zhang H, Kim YK, Govindarajan A, Baba A, Binnie M, Marco Ranieri V, Liu M, Slutsky AS (1999) Effect of adrenoreceptors on endotoxin-induced cytokines and lipid peroxidation in lung explants. Am J Respir Crit Care Med 160:1703–1710

    CAS  PubMed  Google Scholar 

  16. Knudsen JH, Kjaersgaard E, Christensen NJ (1995) Individual lymphocyte subset composition determines cAMP response to isoproterenol in mononuclear cell preparations from peripheral blood. Scand J Clin Lab Invest 55:9–14

    Article  CAS  PubMed  Google Scholar 

  17. Kuroki K, Takahashi HK, Iwagaki H, Murakami T, Kuinose M, Hamanaka S, Minami K, Nishibori M, Tanaka N, Tanemoto K (2004) Beta2-adrenergic receptor stimulation-induced immunosuppressive effects possibly through down-regulation of co-stimulatory molecules, ICAM-1, CD40 and CD14 on monocytes. J Int Med Res 32:465–483

    CAS  PubMed  Google Scholar 

  18. Mustafa SB, Olson MS (1998) Expression of nitric-oxide synthase in rat Kupffer cells is regulated by cAMP. J Biol Chem 273:5073–5080

    Article  CAS  PubMed  Google Scholar 

  19. Yao J, Mackman N, Edgington TS, Fan ST (1997) Lipopolysaccharide induction of the tumor necrosis factor-alpha promoter in human monocytic cells: regulation by Egr-1, c-Jun, and NF-kappaB transcription factors. J Biol Chem 272:1795–1801

    Google Scholar 

  20. Arai K, Wood JP, Osborne NN (2003) Beta-adrenergic receptor agonists and antagonists counteract LPS-induced neuronal death in retinal cultures by different mechanisms. Brain Res 985:176–186

    Article  CAS  PubMed  Google Scholar 

  21. Mazzio E, Becker A, Soliman KF (2002) Characterization of neurotransmitters and dopamine attenuation of inducible nitric oxide synthase in glioma cells. J Neuroimmunol 131:70–82

    Article  CAS  PubMed  Google Scholar 

  22. Nakamura A, Imaizumi A, Yanagawa Y, Niimi R, Kohsaka T (2003) Suppression of tumor necrosis factor-alpha by beta2-adrenoceptor activation: role of mitogen-activated protein kinases in renal mesangial cells. Inflamm Res 52:26–31

    Article  CAS  PubMed  Google Scholar 

  23. Zhang B, Yang L, Konishi Y, Maeda N, Sakanaka M, Tanaka J (2002) Suppressive effects of phosphodiesterase type IV inhibitors on rat cultured microglial cells: comparison with other types of cAMP-elevating agents. Neuropharmacology 42:262–269

    Article  CAS  PubMed  Google Scholar 

  24. Weiss M, Schneider EM, Tarnow J, Mettler S, Krone M, Teschemacher A, Lemoine H (1996) Is inhibition of oxygen radical production of neutrophils by sympathomimetics mediated via beta-2 adrenoceptors? J Pharmacol Exp Ther 278:1105–1113

    CAS  PubMed  Google Scholar 

  25. Youssef HA, Sigurdsson GH, Christenson JT, Owunwanne A (1991) Use of indium-111-labeled transferrin to study plasma extravasation during endotoxin shock and the effects of the beta-2 agonist terbutaline. Am J Physiol Imaging 6:85–89

    CAS  PubMed  Google Scholar 

  26. Schmidt W, Hacker A, Gebhard MM, Martin E, Schmidt H (1998) Dopexamine attenuates endotoxin-induced microcirculatory changes in rat mesentery: role of beta2 adrenoceptors. Crit Care Med 26:1639–1645

    Article  CAS  PubMed  Google Scholar 

  27. Izeboud CA, Hoebe KH, Grootendorst AF, Nijmeijer SM, van Miert AS, Witkamp RR, Rodenburg RJ (2004) Endotoxin-induced liver damage in rats is minimized by beta 2-adrenoceptor stimulation. Inflamm Res 53:93–99

    Article  CAS  PubMed  Google Scholar 

  28. Maris NA, de Vos AF, Dessing MC, Spek CA, Lutter R, Jansen HM, van der Zee JS, Bresser P, van der Poll T (2005) Antiinflammatory effects of salmeterol after inhalation of lipopolysaccharide by healthy volunteers. Am J Respir Crit Care Med 172:878–884

    Article  PubMed  Google Scholar 

  29. Verhoeckx KC, Doornbos RP, van der Greef J, Witkamp RF, Rodenburg RJ (2005) Inhibitory effects of the beta-adrenergic receptor agonist zilpaterol on the LPS-induced production of TNF-alpha in vitro and in vivo. J Vet Pharmacol Ther 28:531–537

    Article  CAS  PubMed  Google Scholar 

  30. Wu JY, Tsou MY, Chen TH, Chen SJ, Tsao CM, Wu CC (2008) Therapeutic effects of melatonin on peritonitis-induced septic shock with multiple organ dysfunction syndrome in rats. J Pineal Res 45:106–116

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants NSC 94-2320-B-016-037, 95-2320-B-016-008 and 96-2320-B-016-002 from the National Science Council and DOD 95-07-02, 96-01-08 and 97-08-01 from the National Defense Ministry, Taiwan, ROC

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Correspondence to Wen-Jinn Liaw.

Additional information

C.-M. Tsao and S.-J. Chen have made equal contribution to this study.

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Tsao, CM., Chen, SJ., Shih, MC. et al. Effects of terbutaline on circulatory failure and organ dysfunction induced by peritonitis in rats. Intensive Care Med 36, 1571–1578 (2010). https://doi.org/10.1007/s00134-010-1839-z

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  • DOI: https://doi.org/10.1007/s00134-010-1839-z

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