Organ-Protective Effects and the Underlying Mechanism of Dexmedetomidine

Bao, Naren two ya; Tang, Bing

doi:10.1155/2020/6136105

Cited by 103 publications

(107 citation statements)

References 105 publications

(123 reference statements)

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“…DEX has pulmonary protective benefits in lung injury cases through its effect on pulmonary vascular ischemia-reperfusion injury and inflammatory cytokine release. 11 Further, DEX improves arterial oxygenation during OLV and decreases the recovery phase duration and postoperative complications in adult patients undergoing thoracic surgery. [12][13][14] However, the underlying molecular mechanism of DEXrelated protective effects on post-VATS lung injury remains unclear.…”

Section: Introductionmentioning

confidence: 97%

<p>Activation of PI3K/Akt/HIF-1α Signaling is Involved in Lung Protection of Dexmedetomidine in Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Pilot Study</p>

Zhu

Zhang

et al. 2020

DDDT

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Background: Lung resection and one lung ventilation (OLV) during video-assisted thoracoscopic surgery (VATS) may lead to acute lung injury. Dexmedetomidine (DEX), a highly selective α 2 adrenergic receptor agonist, improves arterial oxygenation in adult patients undergoing thoracic surgery. The aim of this pilot study was to explore possible mechanism related to lung protection of DEX in patients undergoing VATS. Patients and Methods: Seventy-four patients scheduled for VATS were enrolled in this study. Three timepoints (before anesthesia induction (T 0), 40 min after OLV (T 1), and 10 min after two-lung ventilation (T 2)) of arterial blood gas were obtained. Meanwhile, lung histopathologic examination, immunohistochemistry analysis (occludin and ZO-1), levels of tumor necrosis factor (TNF)-α and interleukin (IL)-6 in lung tissue and plasma, and activation of phosphoinositide-3-kinase (PI3K)/AKT/hypoxia-inducible factor (HIF)-1α signaling were detected. Postoperative outcomes including duration of withdrawing the pleural drainage tube, length of hospital stay, hospitalization expenses, and postoperative pulmonary complications (PPCs) were also recorded. Results: Sixty-seven patients were randomly divided into DEX group (group D, n=33) and control group (group N, n=34). DEX improved oxygenation at T 1 and T 2 (group D vs group N; T 1 : 191.8 ± 49.8 mmHg vs 159.6 ± 48.1 mmHg, P = 0.009; T 2 : 406.0 mmHg [392.2-423.7] vs 374.5 mmHg [340.2-378.2], P = 0.001). DEX alleviated the alveolar capillary epithelial structure damage, increased protein expression of ZO-1 and occludin, inhibited elevation of the expression of TNF-α and IL-6 in lung tissue and plasma, and increased protein expression of p-PI3K, p-AKT and HIF-1α. Dex administered had better postoperative outcomes with less risk of PPCs and hospitalization expenses as well as shorter duration of withdrawing the pleural drainage tube and length of hospital stay. Conclusion: Activation of PI3K/Akt/HIF-1α signaling might be involved in lung protection of DEX in patients undergoing VATS.

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Section: Introductionmentioning

confidence: 97%

<p>Activation of PI3K/Akt/HIF-1α Signaling is Involved in Lung Protection of Dexmedetomidine in Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Pilot Study</p>

Zhu

Zhang

et al. 2020

DDDT

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“…In addition, the logistic regression model including analysis of baseline neurological status, type of surgery as well as intraoperative pro les revealed potential protective effects of dexmedetomidine. Dexmedetomidine has been reported to mitigate neuroin ammatory cascades, and inhibit catecholamine and glutamate release, thereby preventing regional cerebral ischemia [2,11], which commonly occurs during cranial surgery [1,10]. In addition, plausible mechanisms of neuroprotective effects of dexmedetomidine include the attenuation of neuronal necrosis, apoptosis, autophagy through the effects of an increase of focal adhesion kinase phosphorylation in hippocampus, inducing increases of brain derived neurotrophic factor expression [25] as well as inhibiting lipopolysaccharide-induced astrocyte pyroptosis [26].…”

Section: Discussionmentioning

confidence: 99%

“…Because the half-life of serum HMGB1 was only 17 min [33], despite the postoperative serum HMGB1 level remained unchanged in the control group, an increase in intraoperative serum HMGB1 level may likely present otherwise the postoperative resolution should be observed. Dexmedetomidine inhibits the HMGB1/TLR4 pathway [2,34], and its' cytoprotective effects may mitigate release of in ammatory mediators from injured cell [2].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, dexmedetomidine mitigates surgery-related neuroin ammatory cascade [1][2][3]. Numerous studies have revealed that dexmedetomidine inhibits potent initiators and ampli ers of neuroin ammation, namely high motility group box 1 protein (HMGB1), resulting in favorable neurological preservation in various neuronal injury models [2,4]. In addition, intraoperative dexmedetomidine was reported to reduce postoperative delirium in nonneurosurgical populations [5].…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotective Effects of Intraoperative Dexmedetomidine Infusion Combined With Goal-directed Hemodynamic Therapy for Patients Undergoing Cranial Surgery: A Double-blinded Randomized Controlled Trial

Chen

Lee

Yeh

et al. 2020

Preprint

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BackgroundDespite dexmedetomidine may be neuroprotective in patients undergoing cranial surgery by inhibiting neuroinflammation; however, it reduces cardiac output and cerebral blood flow. We proposed that dexmedetomidine infusion combined with goal-directed hemodynamic therapy (GDHT) could improve cranial surgery neurological outcomes without hemodynamic perturbation.MethodsA randomized, double-blind trial was conducted. One hundred sixty adult patients undergoing elective cranial surgery received either dexmedetomidine (0.5 μg kg−1 h−1) or saline during surgery. The goal-directed hemodynamic therapy was used for stroke volume optimization. The proportion of patients who developed postoperative new neurological deficits was compared. The severities of new neurological deficit were assessed by using in-hospital Barthel index changes and the 30-day modified Rankin Scale (mRS). Postoperative delirium was identified using the Intensive Care Delirium Screening Checklist (ICSDC) criteria. The level of a perioperative serum neuroinflammatory mediator, high motility group box 1 protein (HMGB1), was compared.ResultsThe dexmedetomidine group exhibited a lower cardiac index than did the control group (3.0 ± 0.8 vs. 3.4 ± 1.8 L min−1 m−2; p = 0.0482) without lactate accumulation. Fewer patients in the dexmedetomidine group developed new postoperative deficits (26.3% versus 43.8%; p = 0.031) but numbers of patients remained symptomatic neurological deficit before discharge were comparable between the two groups (23.8% vs. 38.8%; p= 0.060). In addition, an attenuated Barthel index decline (−6.3 ± 20.4 vs. −13.6 ± 24.8; p = 0.043), a more favorable 30-day mRS profile (p = 0.013), and a higher incidence of postoperative delirium-free (ICDSC scored 0: 84.6% versus 64.2%; p = 0.012) were observed in the dexmedetomidine group. Furthermore, dexmedetomidine induced a significant decline in perioperative serum HMGB1 level (222.5 ± 408.3 vs. 152.2 ± 280.0 ng mL−1; p = 0.0033).ConclusionsDexmedetomidine infusion combined with GDHT mitigates neuroinflammation during cranial surgery without hemodynamic perturbation, thus achieving neuroprotective effects.Clinical Trial RegistrationProspectively registered at clinicaltrials.gov. (identifier NCT02878707, date of registration: August 25, 2016)

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“…Specifically, DEX activates α 2 adrenergic receptors and acts as a sedative agent by blocking signal transduction in the nucleus coeruleus near the fourth ventricle [ 7 ]. In recent years, clinical and basic research has confirmed that DEX has a protective effect against lung injury [ 8 ]. One study has shown that DEX can reduce lung inflammation in septic rats by inhibiting the TLR4/NF- κ B pathway [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Dexmedetomidine Improves Lung Function by Promoting Inflammation Resolution in Patients Undergoing Totally Thoracoscopic Cardiac Surgery

Cui

Gao

Huang

et al. 2020

Oxidative Medicine and Cellular Longevity

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Objective. Totally thoracoscopic cardiac surgery under cardiopulmonary bypass combined with one-lung ventilation has been identified as the trend in cardiac surgery. The aim of this study was to examine the effects of the selective α2 adrenergic receptor agonist dexmedetomidine on the pulmonary function of patients who underwent mitral valve surgery using the totally thoracoscopic technique. Methods. Fifty-seven patients who underwent thoracoscopic mitral valve surgery between July 2019 and December 2019 were selected. The patients were randomly divided into the control (Con) group (n=28) and the dexmedetomidine (DEX) group (n=29) using the random number table method. Arterial blood gas analyses were performed, and the oxygenation (PaO2/FiO2) and respiratory indexes (P(A-a)O/PaO2) were calculated 5 min after tracheal intubation (T1), 2 h after operation (T2), 6 h after operation (T3), and 24 h after operation (T4). Moreover, the serum cytokines interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and intercellular adhesion molecule-1 (ICAM-1) were detected using the enzyme-linked immunosorbent method at all time points. Chest radiography was performed 24 h after surgery. Peripheral blood samples were collected before and after the operation for a complete hemogram. Additionally, the procalcitonin concentration was measured and recorded when the patients were transported to the intensive care unit (ICU). The postoperative extubation time, length of ICU stay, and pulmonary infection rate were also recorded. Results. Inflammatory reaction after surgery was evident. However, the inflammatory cytokines IL-6, TNF-α, and ICAM-1 in the DEX group were lower than those in the Con group after surgery (T2 to T4; P<0.05). Neutrophil counts and procalcitonin concentration were higher in the Con group than in the DEX group (P<0.05). In addition, in the DEX group, pulmonary exudation on chest radiography was lower, and pulmonary function, as shown by an increase in oxidation index and decrease in the respiratory index, improved after surgery (P<0.05). Moreover, the duration of mechanical ventilation in the Con group was 3.4 h longer than that in the DEX group. Conclusion. Dexmedetomidine has a protective effect on pulmonary function in patients undergoing mitral valve surgery using a totally video-assisted thoracoscopic technique, which may be related to a reduction in the concentration of inflammatory cytokines in the early perioperative period.

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Organ-Protective Effects and the Underlying Mechanism of Dexmedetomidine

Cited by 103 publications

References 105 publications

<p>Activation of PI3K/Akt/HIF-1α Signaling is Involved in Lung Protection of Dexmedetomidine in Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Pilot Study</p>

<p>Activation of PI3K/Akt/HIF-1α Signaling is Involved in Lung Protection of Dexmedetomidine in Patients Undergoing Video-Assisted Thoracoscopic Surgery: A Pilot Study</p>

Neuroprotective Effects of Intraoperative Dexmedetomidine Infusion Combined With Goal-directed Hemodynamic Therapy for Patients Undergoing Cranial Surgery: A Double-blinded Randomized Controlled Trial

Dexmedetomidine Improves Lung Function by Promoting Inflammation Resolution in Patients Undergoing Totally Thoracoscopic Cardiac Surgery

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