Caecal Ligation and Puncture Develops Time Dependent Progression of Sepsis with Multiple Organs Damage and Vascular Dysfunctions in Mice

Authors

  • Smooth Muscle Pharmacology and Molecular Pharmacology Laboratory, Department of Veterinary Pharmacology and Toxicology, Mathura - 281001, Uttar Pradesh
  • Smooth Muscle Pharmacology and Molecular Pharmacology Laboratory, Department of Veterinary Pharmacology and Toxicology, Mathura - 281001, Uttar Pradesh
  • Smooth Muscle Pharmacology and Molecular Pharmacology Laboratory, Department of Veterinary Pharmacology and Toxicology, Mathura - 281001, Uttar Pradesh
  • Department of Veterinary Pathology, College of Veterinary Science and Animal Husbandry U. P. Pandit Deen Dayal Upadhyaya Pashu Chikitsa Vigyan Vishwavidyalaya Evam Go-Anusandhan Sansthan, Mathura – 281001, Uttar Pradesh
  • Smooth Muscle Pharmacology and Molecular Pharmacology Laboratory, Department of Veterinary Pharmacology and Toxicology, Mathura - 281001, Uttar Pradesh
  • Smooth Muscle Pharmacology and Molecular Pharmacology Laboratory, Department of Veterinary Pharmacology and Toxicology, Mathura - 281001, Uttar Pradesh
  • Smooth Muscle Pharmacology and Molecular Pharmacology Laboratory, Department of Veterinary Pharmacology and Toxicology, Mathura - 281001, Uttar Pradesh

DOI:

https://doi.org/10.18311/ti/2021/v28i4/28025

Keywords:

CLP, Early and Late Phase, Histopathology, Sepsis, Vital Organs

Abstract

Sepsis is a dysregulated systemic inflammatory response syndrome that affects multiple organs. However, its effect on vital organs during different phases of sepsis is lacking. Present study was carried out to establish the time dependent changes in the vital organs during different phases of sepsis. Sepsis was induced by caecal ligation and puncture in mice. Sepsis significantly reduced RBC, Hb and WBC counts during both the phases whereas neutrophil count was increased during early phase. There was also a marked fall in lymphocyte count during late phase of sepsis which is an indicative of immunosuppressive state. Significant rise in the plasma ALT, AST, BUN and creatinine levels during early and late phases of sepsis were suggestive of liver and kidney dysfunctions which were further substantiated by histopathological examinations of these vital organs. Sepsis also produced a state of hypoproteinaemia with significant reduction in plasma albumin level. Significant progressive attenuation of vascular reactivity to nor-adrenaline and endothelial relaxation to acetylcholine were also observed in early to late phases of sepsis. However, sodium-nitroprusside-induced endothelium-independent relaxation was unaltered in both early ‘as well as late phase of sepsis. Histopathological examination of lungs, heart and intestine showed progressive degenerative changes which were more prominent with progression from early to late phase of sepsis. Based on the findings of the present study, it may be inferred that caecal ligation and puncture produces time-dependent progression of sepsis in mice affecting multiple organs.

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References

Bosmann M, Ward A. The inflammatory response in sepsis. Trends Immunol. 2013; 34:129–36. https://doi.org/10.1016/j.it.2012.09.004. PMid:23036432 PMCid:PMC3543471

Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: International guidelines for management of severe sepsis and septic shock, 2012. Crit Care Med. 2013; 41:580–37. https://doi.org/10.1097/CCM.0b013e31827e83af. PMid:23353941

Kochanek KD, Smith B. Deaths: preliminary data for 2002. Natl Vital Stat Rep. 2004; 52(13):1–47.

Parrillo JE, Parker MM, Natanson C, Suffredini AF, Danner RL, Cunnion RE, et al. Septic shock in humans. Advances in the understanding of pathogenesis, cardiovascular dysfunction, and therapy. Ann Intern Med. 2006; 113:227–42. https://doi.org/10.7326/0003-4819-113-3-227. PMid:2197912

Poelaert J, Declerck C, Vogelaers D, Colardyn F, Visser CA. Left ventricular systolic and diastolic function in septic shock. Intensive Care Med. 1997; 23:553–60. https://doi.org/10.1007/s001340050372. PMid:9201528

Wicherman KA, Baue AE, Chaudry IH. Sepsis and septic shock: A review of laboratory models and a proposal. J Surg Res. 1980; 29:189–201. https://doi.org/10.1016/0022-4804(80)90037-2

Gibson-Corley KN, Olivier AK, Meyerholz DK. Principles for valid histopathologic scoring in research. Vet Pathol. 2013; 50(6):1007–15. https://doi.org/10.1177/0300985813485099 PMid:23558974 PMCid:PMC3795863

Wang P, Ba ZF, Chaudry IH. Endothelium dependent relaxation is depressed at the macro and microcirculatory levels during sepsis. Am J Physiol. 1995; 269:R998–94. https://doi.org/10.1152/ajpregu.1995.269.5.R988. PMid:7503327

Hubbard WJ, Choudhry M, Schwacha MG, Kerby JD, Rue LW, Bland KI, et al. Cecal ligation and puncture. Shock. 2005; 24:52–7. https://doi.org/10.1097/01.shk.0000191414.94461.7e. PMid:16374373

Choudhury S, Kandasamy K, Maruti BS, Addison MP, Kasa JK, Darzi SA, et al. Atorvastatin along with imipenem attenuates acute lung injury in sepsis through decrease in inflammatory mediators and bacterial load. Eu J Pharmacol. 2015; 765:447–56. https://doi.org/10.1016/j.ejphar.2015.09.009. PMid:26375251

Tyagi A, Sethi AK, Girotra G, Mohta M. The microcirculation in sepsis. Ind J Anaesth. 2009; 53:281–93.

Adamzik M, Hamburger T, Petrat F, Peters J, Groot H, Hartmann. Free hemoglobin concentration in severe sepsis: methods of measurement and prediction of outcome. Crit Care. 2012; 16:R125. https://doi.org/10.1186/cc11425. PMid:22800762 PMCid:PMC35 80706

Jansma G, Buter H, Gerritsen RT, Boerma EC. Is hemoglobin concentration affected by sepsis in the acute phase? Crit. Care. 2013; 17(2):P10. https://doi.org/10.1186/cc11948. PMCid:PMC3642527

Kimmoun A, Ducrocq N, Levy B. Mechanisms of vascular hyporesponsiveness in septic shock. Curr Vasc Pharmacol. 2013; 11:139–49. https://doi.org/10.2174/1570161111311020004. PMid:23506493

Subramani J, Kathirvel K, Leo MD, Kuntamallappanavar G, Singh TU, Mishra SK. Atorvastatin restores the impaired vascular endothelium dependent relaxations mediated by nitric oxide and endothelium-derived hyperpolarizing factors but not hypotension in sepsis. J Cardiovasc Pharmacol. 2009; 54:526–34. https://doi.org/10.1097/FJC.0b013e3181bfafd6. PMid:19755915

Gustot T. Multiple organ failure in sepsis: prognosis and role of systemic inflammatory response. Curr Opin Crit Care. 2011; 17:153–9. https://doi.org/10.1097/MCC.0b013e328344b446. PMid:21346564

Deng M, Scott MJ, Loughran P, Gibson G, Sodhi C, Watkins S, et al. Lipopolysaccharide clearance, bacterial clearance, and systemic inflammatory responses are regulated by cell type-specific functions of TLR4 during sepsis. J Immunol. 2013;190:5152–60. https://doi.org/10.4049/jimmunol.1300496. PMid:23562812 PMCid:PMC3644895

Muftuoglu MA, Aktekin A, Ozdemir NC, Saglam A. Liver injury in sepsis and abdominal compartment syndrome in rats. Surg Today. 2006; 36:519–24. https://doi.org/10.1007/s00595-006-3196-7. PMid:16715421

Wang D, Yin Y, Yao Y. Advances in sepsis-associated liver dysfunction. Burns Trauma. 2014; 2:97–105. https://doi.org/10.4103/2321-3868.132689. PMid:2760 2369. PMCid:PMC5012093

Doi K. Role of kidney injury in sepsis. J Intensive Care. 2016; 4:17. https://doi.org/10.1186/s40560-016-0146-3. PMid:27011788. PMCid:PMC4804517

Doi K, Yuen PST, Eisner C, Hu X, Leelahavanichkul A, Schnermann J, et al. Star reduced production of creatinine limits its use as marker of kidney injury in Sepsis. J Am Soc Nephrol. 2009; 20:1217–21. https://doi.org/10.1681/ASN.2008060617. PMid:19389851. PMCid:PMC2689892

Sun J-K, Sun F, Wang X, Yuan S-T, Zheng S-Y, Mu X-W. Risk factors and prognosis of hypoalbuminemia in surgical septic patients. Peer J. 2015; 3:e1267. https://doi.org/10.7717/peerj.1267. PMid:26557421. PMCid:PMC4636415

Gatta A, Verardo A, Bolognesi M. Hypoalbuminemia. Internal. Emergency Med. 2012; 7: S193–99. https://doi.org/10.1007/s11739-012-0802-0. PMid:23073857

Finfer S, McEvoy S, Bellomo R, McArthur C, Myburgh J, Norton R. Impact of albumin compared to saline on organ function and mortality of patients with severe sepsis. Intensive Care Med. 2011; 37: 86–96. https://doi.org/10.1007/s00134-010-2039-6. PMid:20924555

Luo L, Zhang S, Wang Y, Rahman M, Syk I, Zhang E, et al. Proinflammatory role of neutrophil extracellular traps in abdominal sepsis. Am J Physiol Lung Cell Mol Physiol. 2014; 307: L586–96. https://doi.org/10.1152/ajplung.00365.2013. PMid:25085626

Lucas R, Verin AD, Black SM, Catravas JD. Regulators of endothelial and epithelial barrier integrity and function in acute lung injury. Biochem Pharmacol. 2009; 77:e1763–72. https://doi.org/10.1016/j.bcp.2009.01.014. PMid:19428331 PMCid:PMC4474367

Obinu E, Fanos V, Gerosa C, Fanni D, Loddo C, Ambu R, Faa G. Histological changes in neonatal sepsis. J Pediatr Neonatal Individualized Med. 2014; 3:1–11.

Fay KT, Ford ML, Coopersmith CM. The intestinal microenvironment in sepsis. Biochim Biophys Acta. 2017; S0925–4439:30081–9. https://doi.org/10.1016/j.bbadis.2017.03.005. PMid:28286161 PMCid:PMC5589488

Lyons JD, Coopersmith CM. Pathophysiology of the gut and the microbiome in the Host Response. Pediatr Crit Care Med. 2017; 8:S46–9. https://doi.org/10.1097/PCC.0000000000001046. PMid:28248833. PMCid:PM C5333129

Published

2021-12-22

How to Cite

Singh, P., Nakade, U. P., Sharma, A., Gangwar, N., Choudhury, S., Shukla, A., & Kumar Garg, S. (2021). Caecal Ligation and Puncture Develops Time Dependent Progression of Sepsis with Multiple Organs Damage and Vascular Dysfunctions in Mice. Toxicology International, 28(4), 371–384. https://doi.org/10.18311/ti/2021/v28i4/28025

Issue

Section

Original Research