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Lipopolysaccharide-Induced Ionized Hypocalcemia and Acute Kidney Injury in Carotid Chemo/Baro-Denervated Rats

  • R. FernándezEmail author
  • P. Cortés
  • R. Del Rio
  • C. Acuña-Castillo
  • E. P. Reyes
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 860)

Abstract

The acute kidney injury (AKI) observed during sepsis is due to an uncontrolled release of inflammatory mediators. Septic patients develop electrolytic disturbances and one of the most important is ionized hypocalcemia. AKI adversely affects the function of other organs and hypocalcemia is associated with cardiovascular and respiratory dysfunctions. Since carotid body chemoreceptors modulate the systemic inflammatory response during sepsis syndromes, we used pentobarbitone-anesthetized male Sprague–Dawley rats in control condition (SHAM surgery) and after bilateral carotid neurotomy (carotid chemo/baro-denervated, BCN). We evaluate serum creatinine (CRE), serum neutrophil gelatinase-associated lipocaline (NGAL), ionized calcium (iCa) and cardiac Troponin I (cTnI) 90 min after the IP administration of 15 mg/kg lipopolysaccharide (LPS) or saline. In the SHAM group, LPS failed to induce significant changes CRE, NGAL, or iCa, and increased cTnI. Conversely, in the BCN group LPS increased CRE and NGAL, decreased iCa, and enhanced the increase of cTnI. Our results suggest that carotid chemo/baro-receptors might contribute to the regulation of both renal function and calcemia during sepsis. In addition, results imply that the carotid chemo-baroreceptors serve as an immunosensory organ.

Keywords

Carotid body Sepsis Acute kidney injury Ionized hypocalcemia Cardiac Troponin I 

Notes

Acknowledgments

Supported by FONDECYT 1120976 and UNAB DI-354-13/R (to RF), and UDD CI 23400098 (to EPR).

References

  1. Aguilera IM, Vaughan RS (2000) Calcium and the anaesthetist. Anaesthesia 55:779–790PubMedCrossRefGoogle Scholar
  2. Bagshaw SM, Uchino S, Bellomo R et al (2007) Septic acute kidney injury in critically ill patients: clinical characteristics and outcomes. Clin J Am Soc Nephrol 2:431–439PubMedCrossRefGoogle Scholar
  3. Baum N, Dichoso CC, Carlton CE (1975) Blood urea nitrogen and serum creatinine. Physiology and interpretations. Urology 5:583–588PubMedCrossRefGoogle Scholar
  4. Bone RC, Balk RA, Cerra FB et al (2009) Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee, American College of Chest Physicians/Society of Critical Care Medicine. 1992. Chest 136, e28Google Scholar
  5. Dias CR, Leite HP, Nogueira PC et al (2013) Ionized hypocalcemia is an early event and is associated with organ dysfunction in children admitted to the intensive care unit. J Crit Care 28:810–815PubMedCrossRefGoogle Scholar
  6. Fan J, Zhang B, Shu HF et al (2009) Interleukin-6 increases intracellular Ca2+ concentration and induces catecholamine secretion in rat carotid body glomus cells. J Neurosci Res 87:2757–2762PubMedCrossRefGoogle Scholar
  7. Fernandez R, Acuna-Castillo C (2012) Neural reflex control of inflammation during sepsis syndromes. In: Azedevo L (ed) Sepsis – an ongoing and significant challenge. InTech, Rijeka, pp 133–156Google Scholar
  8. Fernandez R, Gonzalez S, Rey S et al (2008) Lipopolysaccharide-induced carotid body inflammation in cats: functional manifestations, histopathology and involvement of tumour necrosis factor-alpha. Exp Physiol 93:892–907PubMedCrossRefGoogle Scholar
  9. Fernandez R, Nardocci G, Simon F et al (2011) Lipopolysaccharide signaling in the carotid chemoreceptor pathway of rats with sepsis syndrome. Respir Physiol Neurobiol 175:336–348PubMedCrossRefGoogle Scholar
  10. Gomez H, Ince C, De Backer D et al (2014) A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics, and the tubular cell adaptation to injury. Shock 41:3–11PubMedCrossRefPubMedCentralGoogle Scholar
  11. Huang CQ, Ma GZ, Tao MD et al (2009) The relationship among renal injury, changed activity of renal 1-alpha hydroxylase and bone loss in elderly rats with insulin resistance or type 2 diabetes mellitus. J Endocrinol Invest 32:196–201PubMedCrossRefGoogle Scholar
  12. Leelahavanichkul A, Yasuda H, Doi K et al (2008) Methyl-2-acetamidoacrylate, an ethyl pyruvate analog, decreases sepsis-induced acute kidney injury in mice. Am J Physiol Renal Physiol 295:F1825–F1835PubMedCrossRefPubMedCentralGoogle Scholar
  13. Lopes JA, Fernandes P, Jorge S et al (2010) Long-term risk of mortality after acute kidney injury in patients with sepsis: a contemporary analysis. BMC Nephrol 11:9PubMedCrossRefPubMedCentralGoogle Scholar
  14. Maeder M, Fehr T, Rickli H et al (2006) Sepsis-associated myocardial dysfunction: diagnostic and prognostic impact of cardiac troponins and natriuretic peptides. Chest 129:1349–1366PubMedCrossRefGoogle Scholar
  15. Martinez JD, Babu RV, Sharma G (2009) Escherichia coli septic shock masquerading as ST-segment elevation myocardial infarction. Postgrad Med 121:102–105PubMedCrossRefGoogle Scholar
  16. Mehta NJ, Khan IA, Gupta V et al (2004) Cardiac troponin I predicts myocardial dysfunction and adverse outcome in septic shock. Int J Cardiol 95:13–17PubMedCrossRefGoogle Scholar
  17. Nardocci G, Martin A, Abarzua S et al (2015) Sepsis progression to multiple organ dysfunction in carotid chemo/baro-denervated rats treated with lipopolysaccharide. J Neuroimmunol 278:44–52PubMedCrossRefGoogle Scholar
  18. Nguyen HB, Eshete B, Lau KH et al (2013) Serum 1,25-dihydroxyvitamin D: an outcome prognosticator in human sepsis. PLoS One 8, e64348PubMedCrossRefPubMedCentralGoogle Scholar
  19. Reyes EP, Abarzua S, Martin A et al (2012) LPS-induced c-Fos activation in NTS neurons and plasmatic cortisol increases in septic rats are suppressed by bilateral carotid chemodenervation. Adv Exp Med Biol 758:185–190PubMedCrossRefGoogle Scholar
  20. Rich MM, McGarvey ML, Teener JW et al (2002) ECG changes during septic shock. Cardiology 97:187–196PubMedCrossRefGoogle Scholar
  21. Riedemann NC, Guo RF, Ward PA (2003) The enigma of sepsis. J Clin Invest 112:460–467PubMedCrossRefPubMedCentralGoogle Scholar
  22. Shu HF, Wang BR, Wang SR et al (2007) IL-1beta inhibits IK and increases [Ca2+]i in the carotid body glomus cells and increases carotid sinus nerve firings in the rat. Eur J Neurosci 25:3638–3647PubMedCrossRefGoogle Scholar
  23. Singh S, Evans TW (2006) Organ dysfunction during sepsis. Intensive Care Med 32:349–360PubMedCrossRefGoogle Scholar
  24. Soto K, Papoila AL, Coelho S et al (2013) Plasma NGAL for the diagnosis of AKI in patients admitted from the emergency department setting. Clin J Am Soc Nephrol 8:2053–2063PubMedCrossRefPubMedCentralGoogle Scholar
  25. Zapata P, Larrain C, Reyes P et al (2011) Immunosensory signalling by carotid body chemoreceptors. Respir Physiol Neurobiol 178:370–374PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • R. Fernández
    • 1
    Email author
  • P. Cortés
    • 1
  • R. Del Rio
    • 2
  • C. Acuña-Castillo
    • 3
  • E. P. Reyes
    • 4
    • 5
  1. 1.Facultad de Ciencias Biológicas y Facultad de MedicinaUniversidad Andrés BelloSantiagoChile
  2. 2.Laboratory of Cardiorespiratory ControlUniversidad Autónoma de ChileSantiagoChile
  3. 3.Facultad de Química y BiologíaUniversidad de Santiago de ChileSantiagoChile
  4. 4.Centro de Fisiología Celular e Integrativa, Facultad de MedicinaClínica Alemana-Universidad del DesarrolloSantiagoChile
  5. 5.Dirección de InvestigaciónUniversidad Autónoma de ChileSantiagoChile

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