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Correlation of MDR1 gene polymorphisms with anesthetic effect of sevoflurane-remifentanil following pediatric tonsillectomy.

ABSTRACT: The motive of this study was to investigate the collaboration between MDR1 gene polymorphisms and anesthetic effects following pediatric tonsillectomy.All together 178 children undergoing tonsillectomy with preoperative sevoflurane-remifentanil anesthesia were selected. In order to determine MDR1 gene polymorphisms of 3435C?>?T, 1236C?>?T, and 2677G?>?T/A, polymerase chain reaction-restriction fragment length polymorphism was used. Mean arterial pressure (MAP), diastolic blood pressure (DBP), systolic blood pressure (SBP), and heart rate (HR) at T0 (5 mins after the repose), T1 (0?min after tracheal intubation), T2 (5 mins after the tracheal intubation), T3 (0?min after the tonsillectomy), T4 (0?min after removal of the mouth-gag) and T5 (5?min after the extubation) were observed. The visual analog scale (VAS), the face, legs, activity, cry, and consolability (FLACC) pain assessment, and Ramsay sedation score were recorded after the patients gained consciousness. The adverse reactions were also observed.As compared to the CT?+?TT genotype of MDR1 1236C?>?T, the time of induction, respiration recovery, eye-opening, and extubation of children with the CC genotype was found to be shorter (all P?<.05); the MAP, SBP, DBP, and HR were significantly reduced at T5 in children that possessed the CC genotype (all P?<.05), the VAS at postoperative 1, 2, 4, and 8?hours and Ramsay sedation score were decreased, while the FLACC score increased (all P?<.05). It was found that the adverse reaction rate was lower in children bearing the CC genotype (P?<.05).It could be concluded that anesthetic effect in patients with the MDR1 1236C?>?T CC genotype was found to be superior to those carrying the CT?+?TT genotype.

SUBMITTER: Shi NJ

PROVIDER: S-EPMC5478306 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Correlation of MDR1 gene polymorphisms with anesthetic effect of sevoflurane-remifentanil following pediatric tonsillectomy.

Shi Nian-Jun NJ Zhang Wei-Xia WX Zhang Ning N Zhong Li-Na LN Wang Ling-Ping LP

Medicine 20170601 24

<h4>Background</h4>The motive of this study was to investigate the collaboration between MDR1 gene polymorphisms and anesthetic effects following pediatric tonsillectomy.<h4>Methods</h4>All together 178 children undergoing tonsillectomy with preoperative sevoflurane-remifentanil anesthesia were selected. In order to determine MDR1 gene polymorphisms of 3435C > T, 1236C > T, and 2677G > T/A, polymerase chain reaction-restriction fragment length polymorphism was used. Mean arterial pressure (MAP), ...[more]

PMID: 28614221

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Project description:BackgroundAlthough immunomodulatory effects of anesthetics have been increasingly recognized, their underlying molecular mechanisms are not completely understood. Toll-like receptors (TLRs) are one of the major receptors to recognize invading pathogens and danger signals from damaged host tissues to initiate immune responses. Among the TLR family, TLR2 and TLR4 recognize a wide range of ligands and are considered to be important players in perioperative pathophysiology. Based on our recent finding that volatile anesthetics modulate TLR4 function, we tested our hypothesis that they would also modulate TLR2 function.MethodsThe effect of anesthetics isoflurane, sevoflurane, propofol, and dexmedetomidine on TLR2 activation was examined by reporter assays. An anesthetic that affected the activation was subjected to in silico rigid docking simulation on TLR2. To test our prediction that sevoflurane and a TLR1/TLR2 ligand Pam3CSK4 would compete for the same pocket of TLR2, we performed Pam3CSK4 competitive binding assay to TLR2 using HEK cells stably transfected with TLR2 (HEK-TLR2) with or without sevoflurane. We examined the effect of different anesthetics on the functions of human neutrophils stimulated with TLR2 ligands. Kruskal-Wallis test and Mann-Whitney U test were used for statistical analysis.ResultsWe observed that the attenuation of TLR1/TLR2 activation was seen on sevoflurane exposure but not on isoflurane, propofol, or dexmedetomidine exposure. The attenuation of TLR2/TLR6 activation was not seen in any of the anesthetics tested. The rigid docking simulation predicted that sevoflurane and Pam3CSK4 bound to the same pocket of TLR1/TLR2 complex. The binding of Pam3CSK4 to HEK-TLR2 cells was impaired in the presence of sevoflurane, indicating that sevoflurane and Pam3CSK4 competed for the pocket, as predicted in silico. The stimulation of neutrophils with Pam3CSK4 induced L-selection shedding but did not affect phagocytosis and reactive oxygen species production. L-selectin shedding from neutrophils was attenuated only by sevoflurane, consistent with the result of our reporter assays.ConclusionsWe found that TLR1/TLR2 activation was attenuated by sevoflurane, but we found no evidence for attenuation by isoflurane, propofol, or dexmedetomidine at clinically relevant concentrations. Our structural analysis and competition assay supported that sevoflurane directly bound to TLR2 at the interphase of the TLR1/TLR2 complex. Sevoflurane attenuated neutrophil L-selectin shedding, an important step for neutrophil migration.

Dataset Information

Correlation of MDR1 gene polymorphisms with anesthetic effect of sevoflurane-remifentanil following pediatric tonsillectomy.

Publications

Correlation of MDR1 gene polymorphisms with anesthetic effect of sevoflurane-remifentanil following pediatric tonsillectomy.

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