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

Kobayashi, Kensuke; Mimuro, Soichiro; Sato, Tsunehisa; Kobayashi, Atsushi; Kawashima, Shuichi; Makino, Hiroshi; Doi, Matsuyuki; Katoh, Takasumi; Nakajima, Yoshiyuki

doi:10.1007/s00540-018-2568-7

Cited by 16 publications

(17 citation statements)

References 26 publications

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“…Researchers have thus suggested anticoagulation therapy ( 53 ) with some initial positive results ( 124 ). Others have found that dexmedetomidine protects endothelial glycocalyx and increases the survival of rats during heat stroke ( 125 ). Readers are referred to the reviews for details on the results of human and animal studies ( 35 , 38 , 50 ).…”

Section: Pathophysiological Mechanismsmentioning

confidence: 99%

Lessons From Heat Stroke for Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

et al. 2021

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We here provide an overview of the pathophysiological mechanisms during heat stroke and describe similar mechanisms found in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Both conditions are characterized by disturbed homeostasis in which inflammatory pathways play a central role. Splanchnic vasoconstriction, increased gut permeability, gut-related endotoxemia, systemic inflammatory response, central nervous system dysfunction, blood coagulation disorder, endothelial-cell injury, and mitochondrial dysfunction underlie heat stroke. These mechanisms have also been documented in ME/CFS. Moreover, initial transcriptomic studies suggest that similar gene expressions are altered in both heat stroke and ME/CFS. Finally, some predisposing factors for heat stroke, such as pre-existing inflammation or infection, overlap with those for ME/CFS. Notwithstanding important differences - and despite heat stroke being an acute condition - the overlaps between heat stroke and ME/CFS suggest common pathways in the physiological responses to very different forms of stressors, which are manifested in different clinical outcomes. The human studies and animal models of heat stroke provide an explanation for the self-perpetuation of homeostatic imbalance centered around intestinal wall injury, which could also inform the understanding of ME/CFS. Moreover, the studies of novel therapeutics for heat stroke might provide new avenues for the treatment of ME/CFS. Future research should be conducted to investigate the similarities between heat stroke and ME/CFS to help identify the potential treatments for ME/CFS.

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Section: Pathophysiological Mechanismsmentioning

confidence: 99%

Lessons From Heat Stroke for Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

et al. 2021

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“…However, according to a number of studies [89,90] and meta-analysis of randomized controlled trials [118] antioxidant therapy with N-acetylcysteine ameliorated the severity of oxidative stress in pre-eclampsia but had no effects for prevention of PE. Administration of dexmedetomidine, a sedative affecting the α2 adrenaline receptor, which is commonly used in intensive care, has been shown to improve survival and to preserve eGC in a rat heatstroke model [119]. There is some evidence that administration of dexmedetomidine in pre-eclamptic patients was associated with hemodynamic and hormonal stability, without causing severe adverse neonatal outcomes [120][121][122][123].…”

Section: Metforminmentioning

confidence: 99%

Can Endothelial Glycocalyx Be a Major Morphological Substrate in Pre-Eclampsia?

Ziganshina

Yarotskaya

Bovin

et al. 2020

IJMS

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Today pre-eclampsia (PE) is considered as a disease of various theories; still all of them agree that endothelial dysfunction is the leading pathogenic factor. Endothelial dysfunction is a sequence of permanent immune activation, resulting in the change of both the phenotype and the functions of an endothelial cell and of the extracellular layer associated with the cell membrane—endothelial glycocalyx (eGC). Numerous studies demonstrate that eGC mediates and regulates the key functions of endothelial cells including regulation of vascular tone and thromboresistance; and these functions are disrupted during PE. Taking into account that eGC and its components undergo alterations under pathological conditions leading to endothelial activation, it is supposed that eGC plays a certain role in pathogenesis of PE. Envisaging the eGC damage as a key factor of PE, might be a new approach to prevention, treatment, and rehabilitation of patients with PE. This approach could include the development of drugs protecting eGC and promoting regeneration of this structure. Since the issue of PE is far from being solved, any effort in this direction might be valuable.

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“…This suggests that the suppression of excessive inflammation retained EGCX, reduced vascular hyperpermeability, and led to better survival. Previously, we reported that DEX protected EGCX and improved survival in a rat heat stroke model [ 15 ]. A similar effect was observed in the current study, using a rat HS model, and we showed that this was related to an anti-inflammatory mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies reported that DEX has anti-inflammatory effects mediated via cholinergic anti-inflammatory pathways [ 12 , 13 , 14 ]. In addition, we reported that DEX protected glycocalyx in a rat heat stroke model [ 15 ]. However, the effect of DEX on EGCX in HS is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine suppresses serum syndecan-1 elevation and improves survival in a rat hemorrhagic shock model

et al. 2022

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

Cited by 16 publications

References 26 publications

Lessons From Heat Stroke for Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Lessons From Heat Stroke for Understanding Myalgic Encephalomyelitis/Chronic Fatigue Syndrome

Can Endothelial Glycocalyx Be a Major Morphological Substrate in Pre-Eclampsia?

Dexmedetomidine suppresses serum syndecan-1 elevation and improves survival in a rat hemorrhagic shock model

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