Dexmedetomidine Suppresses Serum Syndecan-1 Elevation and Improves Survival in a Rat Hemorrhagic Shock Model

Overview

Journal Exp Anim

Date 2022 Feb 3

PMID 35110424

Authors

Atsushi Kobayashi

Soichiro Mimuro

Takasumi Katoh

Kensuke Kobayashi

Tsunehisa Sato

Truong Sang Kien

Yoshiki Nakajima

Affiliations

Soon will be listed here.

Abstract

Hemorrhagic shock causes vascular endothelial glycocalyx (EGCX) damage and systemic inflammation. Dexmedetomidine (DEX) has anti-inflammatory and EGCX-protective effects, but its effect on hemorrhagic shock has not been investigated. Therefore, we investigated whether DEX reduces inflammation and protects EGCX during hemorrhagic shock. Anesthetized Sprague-Dawley rats were randomly assigned to five groups (n=7 per group): no shock (SHAM), hemorrhagic shock (HS), hemorrhagic shock with DEX (HS+DEX), hemorrhagic shock with DEX and the α7 nicotinic type acetylcholine receptor antagonist methyllycaconitine citrate (HS+DEX/MLA), and hemorrhagic shock with MLA (HS+MLA). HS was induced by shedding blood to a mean blood pressure of 25-30 mmHg, which was maintained for 30 min, after which rats were resuscitated with Ringer's lactate solution at three times the bleeding volume. The survival rate was assessed up to 3 h after the start of fluid resuscitation. Serum tumor necrosis factor-alpha (TNF-α) and syndecan-1 concentrations, and wet-to-dry ratio of the heart were measured 90 min after the start of fluid resuscitation. The survival rate after 3 h was significantly higher in the HS+DEX group than in the HS group. Serum TNF-α and syndecan-1 concentrations, and the wet-to-dry ratio of heart were elevated by HS, but significantly decreased by DEX. These effects were antagonized by MLA. DEX suppressed the inflammatory response and serum syndecan-1 elevation, and prolonged survival in rats with HS.

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References

Kobayashi K, Mimuro S, Sato T, Kobayashi A, Kawashima S, Makino H . Dexmedetomidine preserves the endothelial glycocalyx and improves survival in a rat heatstroke model. J Anesth. 2018; 32(6):880-885. DOI: 10.1007/s00540-018-2568-7. View

Tamura T, Sano M, Matsuoka T, Yoshizawa J, Yamamoto R, Katsumata Y . Hydrogen Gas Inhalation Attenuates Endothelial Glycocalyx Damage and Stabilizes Hemodynamics in a Rat Hemorrhagic Shock Model. Shock. 2020; 54(3):377-385. PMC: 7458091. DOI: 10.1097/SHK.0000000000001459. View

Rahbar E, Cardenas J, Baimukanova G, Usadi B, Bruhn R, Pati S . Endothelial glycocalyx shedding and vascular permeability in severely injured trauma patients. J Transl Med. 2015; 13:117. PMC: 4397670. DOI: 10.1186/s12967-015-0481-5. View

Lee W, Slutsky A . Sepsis and endothelial permeability. N Engl J Med. 2010; 363(7):689-91. DOI: 10.1056/NEJMcibr1007320. View

Zhang X, Liu Z, Wen S, Li Y, Li Y, Yao X . Dexmedetomidine administration before, but not after, ischemia attenuates intestinal injury induced by intestinal ischemia-reperfusion in rats. Anesthesiology. 2012; 116(5):1035-46. DOI: 10.1097/ALN.0b013e3182503964. View

Okada H, Takemura G, Suzuki K, Oda K, Takada C, Hotta Y . Three-dimensional ultrastructure of capillary endothelial glycocalyx under normal and experimental endotoxemic conditions. Crit Care. 2017; 21(1):261. PMC: 5651619. DOI: 10.1186/s13054-017-1841-8. View

Mimuro S, Katoh T, Suzuki A, Yu S, Adachi Y, Uraoka M . Deterioration of myocardial injury due to dexmedetomidine administration after myocardial ischaemia. Resuscitation. 2010; 81(12):1714-7. DOI: 10.1016/j.resuscitation.2010.07.021. View

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(3):538-45. DOI: 10.1016/j.resuscitation.2007.01.032. View

Tan F, Chen Y, Yuan D, Gong C, Li X, Zhou S . Dexmedetomidine protects against acute kidney injury through downregulating inflammatory reactions in endotoxemia rats. Biomed Rep. 2015; 3(3):365-370. PMC: 4467244. DOI: 10.3892/br.2015.427. View

10.

Bashandy G . Implications of recent accumulating knowledge about endothelial glycocalyx on anesthetic management. J Anesth. 2014; 29(2):269-78. DOI: 10.1007/s00540-014-1887-6. View

11.

Liu H, Xiao X, Sun C, Sun D, Li Y, Yang M . Systemic inflammation and multiple organ injury in traumatic hemorrhagic shock. Front Biosci (Landmark Ed). 2015; 20(6):927-33. DOI: 10.2741/4347. View

12.

Huston J, Tracey K . The pulse of inflammation: heart rate variability, the cholinergic anti-inflammatory pathway and implications for therapy. J Intern Med. 2010; 269(1):45-53. PMC: 4527046. DOI: 10.1111/j.1365-2796.2010.02321.x. View

13.

Rosas-Ballina M, Tracey K . Cholinergic control of inflammation. J Intern Med. 2009; 265(6):663-79. PMC: 4540232. DOI: 10.1111/j.1365-2796.2009.02098.x. View

14.

Liu Z, Wang Y, Ning Q, Gong C, Zhang Y, Zhang L . The role of spleen in the treatment of experimental lipopolysaccharide-induced sepsis with dexmedetomidine. Springerplus. 2015; 4:800. PMC: 4688290. DOI: 10.1186/s40064-015-1598-y. View

15.

Xiang H, Hu B, Li Z, Li J . Dexmedetomidine controls systemic cytokine levels through the cholinergic anti-inflammatory pathway. Inflammation. 2014; 37(5):1763-70. DOI: 10.1007/s10753-014-9906-1. View

16.

Barnaby D, Ferrick K, Kaplan D, Shah S, Bijur P, Gallagher E . Heart rate variability in emergency department patients with sepsis. Acad Emerg Med. 2002; 9(7):661-70. DOI: 10.1111/j.1553-2712.2002.tb02143.x. View

17.

Cao R, Tang L, Xia Z, Xia R . Endothelial glycocalyx as a potential theriapeutic target in organ injuries. Chin Med J (Engl). 2019; 132(8):963-975. PMC: 6595754. DOI: 10.1097/CM9.0000000000000177. View

18.

Schmidt E, Yang Y, Janssen W, Gandjeva A, Perez M, Barthel L . The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med. 2012; 18(8):1217-23. PMC: 3723751. DOI: 10.1038/nm.2843. View

19.

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(2):199-205. DOI: 10.1538/expanim.59.199. View

20.

Truong S, Katoh T, Mimuro S, Sato T, Kobayashi K, Nakajima Y . Inhalation of 2% Hydrogen Improves Survival Rate and Attenuates Shedding of Vascular Endothelial Glycocalyx in Rats with Heat Stroke. Shock. 2021; 56(4):593-600. DOI: 10.1097/SHK.0000000000001797. View