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Dexmedetomidine preserves the endothelial glycocalyx and improves survival in a rat heatstroke model

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Abstract

Purpose

Heatstroke causes systemic inflammation, followed by vascular endothelial damage. The normal vascular endothelium is coated by endothelial glycocalyx (EGCX). Dexmedetomidine (DEX) has an anti-inflammatory effect, but there has been little investigation on the influence of heatstroke on EGCX and the effect of DEX on this condition. Therefore, we examined whether EGCX was disrupted in heatstroke and if DEX improved survival and preserves EGCX.

Methods

Anesthetized Wistar rats were randomly assigned to three groups: a DEX group treated with DEX (5 µg/kg/h) and 0.9% saline infused continuously at 10 ml/kg/h during heat exposure; a NSS group given 0.9% saline during heat exposure; and a SHAM group given 0.9% saline alone without heat exposure. Heatstroke was induced by exposure to an ambient temperature of 40 °C with relative humidity of 60%. The survival rate was assessed up to 2 h after the start of heat exposure. Plasma levels of syndecan-1 and the thickness of EGCX using electron microscopy were measured when the systolic blood pressure fell to less than 80 mmHg.

Results

The survival rate after 2 h of heat exposure was significantly higher in the DEX group compared to the NSS group (89% vs. 22%, P = 0.004). Plasma levels of syndecan-1 were 0.6 ± 1.3, 9.7 ± 5.9, and 2.1 ± 3.4 ng/ml in the SHAM, NSS and DEX groups, respectively (P = 0.013). The thickness of EGCX was significantly higher in the DEX group compared with the NSS group (P = 0.001).

Conclusions

EGCX was disrupted in heatstroke, and DEX improved survival and preserved EGCX.

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References

  1. Hifumi T, Kondo Y, Shimizu K, Miyake Y. Heat stroke. J Intensive Care. 2018;6:1–8.

    Article  Google Scholar 

  2. Bouchama AKJ. Heat stroke. N Engl J Med. 2002;346:1978–88.

    Article  CAS  Google Scholar 

  3. Nakajima Y, Baudry N, Duranteau J, Vicaut E. Effects of vasopressin, norepinephrine, and l-arginine on intestinal microcirculation in endotoxemia. Crit Care Med. 2006;34:1752–7.

    Article  CAS  Google Scholar 

  4. Lee WL, Slutsky AS. Sepsis and Endothelial Permeability. N Engl J Med. 2010;363:689–91.

    Article  CAS  Google Scholar 

  5. Kataoka H, Ushiyama A, Akimoto Y, Matsubara S, Kawakami H, Iijima T. Structural behavior of the endothelial glycocalyx is associated with pathophysiologic status in septic mice: an integrated approach to analyzing the behavior and function of the glycocalyx using both electron and fluorescence intravital microscopy. Anesth Analg. 2017;125:874–83.

    Article  Google Scholar 

  6. Becker BF, Chappell D, Bruegger D, Annecke T, Jacob M. Therapeutic strategies targeting the endothelial glycocalyx: Acute deficits, but great potential. Cardiovasc Res. 2010;87:300–10.

    Article  CAS  Google Scholar 

  7. Chappell D, Westphal M, Jacob M. The impact of the glycocalyx on microcirculatory oxygen distribution in critical illness. Curr Opin Anaesthesiol. 2009;22:155–62.

    Article  Google Scholar 

  8. Sano H, Doi M, Mimuro S, Yu S, Kurita T, Sato S. Evaluation of the Hypnotic and Hemodynamic Effects of Dexmedetomidine on Propofol-Sedated Swine. Exp Anim. 2010;59:199–205.

    Article  CAS  Google Scholar 

  9. Kawazoe Y, Miyamoto K, Morimoto T, Yamamoto T, Fuke A, Hashimoto A, Koami H, Beppu S, Katayama Y, Itoh M, Ohta Y, Yamamura H. Effect of dexmedetomidine on mortality and ventilator-free days in patients requiring mechanical ventilation with sepsis. JAMA. 2017;317:1321–8.

    Article  CAS  Google Scholar 

  10. Taniguchi T, Kidani Y, Kanakura H, Takemoto Y, Yamamoto K. Effects of dexmedetomidine on mortality rate and inflammatory responses to endotoxin-induced shock in rats. Crit Care Med. 2004;32:1322–6.

    Article  CAS  Google Scholar 

  11. Yeh YC, Wu CY, Cheng YJ, Liu CM, Hsiao JK, Chan WS, Wu ZG, Yu LCH, Sun WZ. Effects of dexmedetomidine on intestinal microcirculation and intestinal epithelial barrier in endotoxemic rats. Anesthesiology. 2016;125:355–67.

    Article  CAS  Google Scholar 

  12. Xia ZN, Zong Y, Zhang ZT, Chen JK, Ma XJ, Liu YG, Zhao LJ, Lu GC. Dexmedetomidine protects against multi-organ dysfunction induced by heatstroke via sustaining the intestinal integrity. Shock. 2017;48:260–9.

    Article  CAS  Google Scholar 

  13. Taniguchi T, Kurita A, Kobayashi K, Yamamoto K, Inaba H. Dose- and time-related effects of dexmedetomidine on mortality and inflammatory responses to endotoxin-induced shock in rats. J Anesth. 2008;22:221–8.

    Article  Google Scholar 

  14. Zhang X-Y, Liu Z-M, Wen S-H, Li Y-S, Li Y, Yao X, Huang W-Q, Liu K-X. Dexmedetomidine administration before, but not after, ischemia attenuates intestinal injury induced by intestinal ischemia-reperfusion in rats. Anesthesiology. 2012;116:1035–46.

    Article  CAS  Google Scholar 

  15. Bashandy GM. Implications of recent accumulating knowledge about endothelial glycocalyx on anesthetic management. J Anesth. 2015;29:269–78.

    Article  Google Scholar 

  16. Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. A high admission syndecan-1 Level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Ann Surg. 2011;254:194–200.

    Article  Google Scholar 

  17. Miranda ML, Balarini MM, Bouskela E. Dexmedetomidine attenuates the microcirculatory derangements evoked by experimental sepsis. Anesthesiology. 2015;122:619–30.

    Article  CAS  Google Scholar 

  18. Strunden MS, Bornscheuer A, Schuster A, Kiefmann R, Goetz AE, Heckel K. Glycocalyx degradation causes microvascular perfusion failure in the ex vivo perfused mouse lung: Hydroxyethyl starch 130/0.4 pretreatment attenuates this response. Shock. 2012;38:559–66.

    Article  CAS  Google Scholar 

  19. Yamakawa K, Matsumoto N, Imamura Y, Muroya T, Yamada T, Nakagawa J, Shimazaki J, Ogura H, Kuwagata Y, Shimazu T. Electrical vagus nerve stimulation attenuates systemic inflammation and improves survival in a rat heatstroke model. PLoS One. 2013;8:e56728.

    Article  CAS  Google Scholar 

  20. Liu Z, Wang Y, Ning Q, Gong C, Zhang Y, Zhang L, Bu X, Jing G. The role of spleen in the treatment of experimental lipopolysaccharide—induced sepsis with dexmedetomidine. Springerplus. 2015;4:800.

    Article  Google Scholar 

  21. Okada H, Takemura G, Suzuki K, Oda K, Takada C, Hotta Y, Miyazaki N, Tsujimoto A, Muraki I, Ando Y, Zaikokuji R, Matsumoto A, Kitagaki H, Tamaoki Y, Usui T, Doi T, Yoshida T, Yoshida S, Ushikoshi H, Toyoda I, Ogura S. Three-dimensional ultrastructure of capillary endothelial glycocalyx under normal and experimental endotoxemic conditions. Crit Care. 2017;21:261.

    Article  Google Scholar 

  22. Inagawa R, Okada H, Takemura G, Suzuki K, Takada C, Yano H, Ando Y, Usui T, Hotta Y, Miyazaki N, Tsujimoto A, Zaikokuji R, Matsumoto A, Kawaguchi T, Doi T, Yoshida T, Yoshida S, Kumada K, Ushikoshi H, Toyoda I, Ogura S. Ultrastructural alteration of pulmonary capillary endothelial glycocalyx during endotoxemia. Chest. 2018;154:317–25.

    Article  Google Scholar 

  23. Van den Berg BM, Vink H, Spaan JAE. The endothelial glycocalyx protects against myocardial edema. Circ Res. 2003;92:592–4.

    Article  Google Scholar 

  24. Rehm M, Bruegger D, Christ F, Conzen P, Thiel M, Jacob M, Chappell D, Stoeckelhuber M, Welsch U, Reichart B, Peter K, Becker BF. Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation. 2007;116:1896–906.

    Article  CAS  Google Scholar 

  25. Mimuro S, Katoh T, Suzuki A, Yu S, Adachi YU, Uraoka M, Sano H, Sato S. Deterioration of myocardial injury due to dexmedetomidine administration after myocardial ischaemia. Resuscitation. 2010;81:1714–7.

    Article  CAS  Google Scholar 

  26. Okada H, Kurita T, Mochizuki T, Morita K, Sato S. The cardioprotective effect of dexmedetomidine on global ischaemia in isolated rat hearts. Resuscitation. 2007;74:538–45.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Anesthesiology and Intensive Care, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka, 431-3192, Japan

    Kensuke Kobayashi, Soichiro Mimuro, Tsunehisa Sato, Atsushi Kobayashi, Shingo Kawashima, Hiroshi Makino, Matsuyuki Doi, Takasumi Katoh & Yoshiki Nakajima

Authors
  1. Kensuke Kobayashi
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  2. Soichiro Mimuro
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  3. Tsunehisa Sato
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  4. Atsushi Kobayashi
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  5. Shingo Kawashima
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  6. Hiroshi Makino
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  7. Matsuyuki Doi
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  8. Takasumi Katoh
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  9. Yoshiki Nakajima
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Correspondence to Soichiro Mimuro.

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Kobayashi, K., Mimuro, S., Sato, T. et al. Dexmedetomidine preserves the endothelial glycocalyx and improves survival in a rat heatstroke model. J Anesth 32, 880–885 (2018). https://doi.org/10.1007/s00540-018-2568-7

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  • DOI: https://doi.org/10.1007/s00540-018-2568-7

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