Anaesthetic mechanisms: update on the challenge of unravelling the mystery of anaesthesia

Lugli, Andrea Kopp; Yost, C. Spencer; Kindler, Christoph

doi:10.1097/eja.0b013e32832d6b0f

Cited by 93 publications

(77 citation statements)

References 154 publications

(145 reference statements)

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“…The molecular basis of anesthetic action involves membrane proteins or ion channels [20, 21]. The resultant effect of anaesthesia is produced by either increasing the inhibition of postsynaptic excitability or by decreasing presynaptic (excitatory) neurotransmitter release.…”

Section: Discussionmentioning

confidence: 99%

Expression of anaesthetic and analgesic drug target genes in excised breast tumour tissue: Association with clinical disease recurrence or metastasis

et al. 2017

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BackgroundRetrospective analyses suggest anaesthetic-analgesics technique during cancer surgery may affect recurrence/metastasis. This could involve direct effects of anaesthetic-analgesic drugs on cancer cells. While μ-opioid receptor over-expression in lung tumours is associated with greater metastasis, other anaesthetic-analgesic receptor targets in cancer recurrence/metastasis remain unexplored. Therefore, we evaluated the association between genetic expression of anaesthetic-analgesic receptor targets and recurrence/metastasis, using a repository of breast cancer gene expression and matching clinical data.MethodsA list of 23 genes encoding for the most prominent anaesthetic-analgesic receptor targets was compiled. This was processed through BreastMark- an algorithm integrating gene expression data from ~17,000 samples and clinical data from >4,500 breast cancer samples. Gene expression data was dichotomized using disease-free survival (survival without recurrence) and distant disease-free survival (survival without metastasis) as end points. Hazard ratios were calculated by Cox-regression analysis. Enrichment for prognostic markers was determined by randomly choosing 23-member gene lists from all available genes, calculating how often >5 significant markers were observed and adjusting p-values for multiple testing. This was repeated 10,000 times and an empirical p-value calculated.ResultsOf 23 selected genes, 9 were significantly associated with altered rates of metastasis and 4 with recurrence on univariate analysis. Adjusting for multiple testing, 5 of these 9 genes remained significantly associated with metastasis, non with recurrence. This ratio of genes (5/23) was not significantly enriched for markers of metastasis (p = 0.07).ConclusionSeveral anaesthetic-analgesic receptor genes were associated with metastatic spread in breast cancer. Overall there was no significant enrichment in prognostic markers of metastasis, although a trend was observed.

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Section: Discussionmentioning

confidence: 99%

Expression of anaesthetic and analgesic drug target genes in excised breast tumour tissue: Association with clinical disease recurrence or metastasis

et al. 2017

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“…These anesthetics vary in their chemical structures and target receptors [26,27]. Ketamine is an N -methyl- D -aspartate receptor antagonist and dexmedetomidine is an α 2 adrenoceptor agonist [1].…”

Section: Discussionmentioning

confidence: 99%

Differential Effects of Intravenous Anesthetics on PDGF-BB-Induced Vascular Smooth Muscle Cell Migration

Iida¹,

Tanabe²,

Kozawa³

et al. 2014

Cell Physiol Biochem

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Background: Intravenous anesthetics are used during the perioperative and/or postoperative period in critically ill patients. Vascular smooth muscle cells (VSMCs) play important roles in vascular injury repair or restenosis after intervention. We previously reported that platelet-derived growth factor (PDGF)-BB induces VSMC migration via extracellular signal-regulated kinase (ERK) and Akt in a VSMC line, A10 cells. In the present study, we investigated the effects of intravenous anesthetics on PDGF-BB-induced VSMC migration and the mechanism. Methods: VSMCs migration was assessed using Boyden chamber, and phosphorylation of each protein kinase was analyzed by Western blotting. Results: Propofol or midazolam but not ketamine or dexmedetomidine suppressed PDGF-BB-induced A10 cells migration in a concentration-dependent manner. The suppressive effects on migration were observed also in human aortic smooth muscle cells. Propofol or midazolam did not affect phosphorylation of PDGF receptor β in A10 cells. Propofol or midazolam failed to affect PDGF-BB-induced phosphorylation of ERK or Akt. On the other hand, propofol or midazolam attenuated PDGF-BB-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK), but did not affect phosphorylation of stress-activated protein kinase/c-Jun N-terminal kinase. Both ketamine and dexmedetomidine had no effect on the phosphorylation of p38 MAPK induced by PDGF-BB. Conclusion: These results strongly suggest that propofol or midazolam inhibits VSMC migration by PDGF-BB via suppression of p38 MAPK activation. Propofol or midazolam may affect VSMC function in critically ill patients.

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“…For these reasons, desflurane is an anaesthetic agent that can maintain sufficient amnesia and anaesthesia levels at a low MAC (0.5 MAC). [16][17][18] The tcMEP responses in our study were sufficient in the estimated time and amplitudes, in both of the TIVA and desflurane groups. We did not determine neurological deficit in our patients in their intraoperative, and postoperative, controls.…”

Section: Resultsmentioning

confidence: 69%

A comparison of the effects of desflurane and total intravenous anaesthesia on the motor evoked responses in scoliosis surgery

Isik¹,

Turan

Abitağaoğlu

et al. 2017

Int J Res Med Sci

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Background: In the present study, we compared the effects of total intravenous anaesthesia (TIVA) and desflurane anaesthesia on tcMEPs in scoliosis surgery.Methods: The study included 45 patients between the ages of 18 to 50 years, and classified as ASAI-II; which were planned to undergo posterior fusion/instrumentation operations for elective scoliosis. Anaesthesia was maintained using 50-150 mcg/kg/min propofol in Group T(TIVA), and desflurane (0.5 MAC) in Group D, and with infusions of 0.05-0.3 mcg/kg/min remifentanil at 50 % O2 + air in both groups, by applying drugs at doses so that bispectral index (BIS) would be maintained between 40 and 60 throughout the course of anaesthesia. The tcMEP responses were measured four times during the operation, and BIS, train-of-four (TOF), mean arterial pressure (MAP), heart rate(HR), and end tidal CO2(ETCO2) values were recorded simultaneously. In both group the anaesthesia was ended at the final surgical suture. The recovery parameters were recorded.Results: The groups were found not to differ regarding the demographic characteristics, duration of the anaesthesia and the surgery, remifentanil dosage, tcMEP, the simultaneously recorded TOF, MAP, HR and ETCO2 values, and the amount of perioperative bleeding. The cooperation time and the orientation time were shorter in group D. The tcMEP responses were recorded in the appropriate times and amplitudes in both groups. Conclusions: TIVA is primarily used in routine applications in spinal surgery; however our study results revealed that 0.5 MAC desflurane may also be safely used in association with remifentanil, with the resultant correct tcMEP responses.

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Anaesthetic mechanisms: update on the challenge of unravelling the mystery of anaesthesia

Cited by 93 publications

References 154 publications

Expression of anaesthetic and analgesic drug target genes in excised breast tumour tissue: Association with clinical disease recurrence or metastasis

Expression of anaesthetic and analgesic drug target genes in excised breast tumour tissue: Association with clinical disease recurrence or metastasis

Differential Effects of Intravenous Anesthetics on PDGF-BB-Induced Vascular Smooth Muscle Cell Migration

A comparison of the effects of desflurane and total intravenous anaesthesia on the motor evoked responses in scoliosis surgery

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