Patient with anaesthesiaAnaesthesia makes up the largest hospital speciality and has a huge role to play in nearly every aspect of any hospital from operating 
theatres to accident and emergency, to the labour ward, and to intensive care. Our research ranges from basic molecular research into mechanisms of anaesthesia to investigating the clinical impact of novel anaesthetic agents. 

Our research covers the entirety of patient’s perioperative journey and through this, we aim to deliver the greatest impact. The section has been pioneering in the development of novel technologies to facilitate the delivery of anaesthetic agents and has also made pivotal in-roads into the mechanism of action of anaesthetic agents and their wider application to other diseases (such as their protective roles in brain injury and in cancer).

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  • Journal article
    Bertaccini EJ, Dickinson R, Trudell JR, Franks NPet al., 2014,

    Molecular modeling of a tandem two pore domain potassium channel reveals a putative binding Site for general anesthetics

    , ACS Chemical Neuroscience, Vol: 5, Pages: 1246-1252, ISSN: 1948-7193

    Anesthetics are thought to mediate a portion of their activity via binding to and modulation of potassium channels. In particular, tandem pore potassium channels (K2P) are transmembrane ion channels whose current is modulated by the presence of general anesthetics and whose genetic absence has been shown to confer a level of anesthetic resistance. While the exact molecular structure of all K2P forms remains unknown, significant progress has been made toward understanding their structure and interactions with anesthetics via the methods of molecular modeling, coupled with the recently released higher resolution structures of homologous potassium channels to act as templates. Such models reveal the convergence of amino acid regions that are known to modulate anesthetic activity onto a common three- dimensional cavity that forms a putative anesthetic binding site. The model successfully predicts additional important residues that are also involved in the putative binding site as validated by the results of suggested experimental mutations. Such a model can now be used to further predict other amino acid residues that may be intimately involved in the target-based structure–activity relationships that are necessary for anesthetic binding.

  • Journal article
    Boshier PR, Marczin N, Hanna GB, 2015,

    Pathophysiology of acute lung injury following esophagectomy

    , DISEASES OF THE ESOPHAGUS, Vol: 28, Pages: 797-804, ISSN: 1120-8694
  • Journal article
    Cristescu SM, Kiss R, Hekkert STL, Dalby M, Harren FJM, Risby TH, Marczin Net al., 2014,

    Real-time monitoring of endogenous lipid peroxidation by exhaled ethylene in patients undergoing cardiac surgery

    , AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY, Vol: 307, Pages: L509-L515, ISSN: 1040-0605

    Pulmonary and systemic organ injury produced by oxidative stress including lipid peroxidation is a fundamental tenet of ischemia-reperfusion injury, inflammatory response to cardiac surgery, and cardiopulmonary bypass (CPB) but is not routinely measured in a surgically relevant time frame. To initiate a paradigm shift toward noninvasive and real-time monitoring of endogenous lipid peroxidation, we have explored pulmonary excretion and dynamism of exhaled breath ethylene during cardiac surgery to test the hypothesis that surgical technique and ischemia-reperfusion triggers lipid peroxidation. We have employed laser photoacoustic spectroscopy to measure real-time trace concentrations of ethylene from the patient breath and from the CPB machine. Patients undergoing aortic or mitral valve surgery-requiring CPB (n = 15) or off-pump coronary artery bypass surgery (OPCAB) (n = 7) were studied. Skin and tissue incision by diathermy caused striking (>30-fold) increases in exhaled ethylene resulting in elevated levels until CPB. Gaseous ethylene in the CPB circuit was raised upon the establishment of CPB (>10-fold) and decreased over time. Reperfusion of myocardium and lungs did not appear to enhance ethylene levels significantly. During OPCAB surgery, we have observed increased ethylene in 16 of 30 documented reperfusion events associated with coronary and aortic anastomoses. Therefore, novel real-time monitoring of endogenous lipid peroxidation in the intraoperative setting provides unparalleled detail of endogenous and surgery-triggered production of ethylene. Diathermy and unprotected regional myocardial ischemia and reperfusion are the most significant contributors to increased ethylene.

  • Journal article
    Mohite PN, Sabashnikov A, Patil NP, Saez DG, Zych B, Popov AF, Weymann A, Wahlers T, Marczin N, DeRobertis F, Bahrami T, Amrani M, Simon ARet al., 2014,

    Short-term ventricular assist device in post-cardiotomy cardiogenic shock: factors influencing survival

    , JOURNAL OF ARTIFICIAL ORGANS, Vol: 17, Pages: 228-235, ISSN: 1434-7229
  • Journal article
    Vizcaychipi MP, Watts HR, O'Dea KP, Lloyd DG, Penn JW, Wan Y, Pac-Soo C, Takata M, Ma Det al., 2014,

    The Therapeutic Potential of Atorvastatin in a Mouse Model of Postoperative Cognitive Decline

    , ANNALS OF SURGERY, Vol: 259, Pages: 1235-1244, ISSN: 0003-4932
  • Journal article
    Vives M, Wijeysundera D, Marczin N, Monedero P, Rao Vet al., 2014,

    Cardiac surgery-associated acute kidney injury

    , INTERACTIVE CARDIOVASCULAR AND THORACIC SURGERY, Vol: 18, Pages: 637-645, ISSN: 1569-9293
  • Journal article
    Lyman M, Lloyd DG, Ji X, Vizcaychipi MP, Ma Det al., 2014,

    Neuroinflammation: The role and consequences

    , NEUROSCIENCE RESEARCH, Vol: 79, Pages: 1-12, ISSN: 0168-0102
  • Journal article
    Harris K, Armstrong SP, Campos-Pires R, Kiru L, Franks NP, Dickinson Ret al., 2013,

    Neuroprotection against traumatic brain injury by xenon but not argon, is mediated by inhibition at the NMDA receptor glycine site

    , Anesthesiology, Vol: 119, Pages: 1137-1148, ISSN: 1528-1175

    Background. The inert anesthetic gas xenon is neuroprotective in models of brain injury. Weinvestigate the neuroprotective mechanisms of the inert gases xenon, argon, krypton, neon andhelium in an in vitro model of traumatic brain injury.Methods. We use an in vitro model using mouse organotypic hippocampal brain-slices, subjectedto a focal mechanical trauma, with injury quantified by propidium-iodide fluorescence. Patch-clampelectrophysiology is used to investigate the effect of the inert gases on N-methyl-D-aspartate(NMDA)-receptors and TREK-1 channels, two molecular targets likely to play a role inneuroprotection.Results. Xenon(50%) and, to a lesser extent, argon(50%) are neuroprotective against traumaticinjury when applied following injury [xenon 43±1% protection 72hours after injury (N=104); argon30±6% protection (N=44); mean±SEM]. Helium, neon and krypton are devoid of neuroprotectiveeffect. Xenon(50%) prevents development of secondary injury up to 48 hours after trauma.Argon(50%) attenuates secondary injury, but is less effective than xenon [xenon 50±5% reductionin secondary injury 72hours after injury (N=104); argon 34±8% reduction (N=44); mean±SEM].Glycine reverses the neuroprotective effect of xenon, but not argon, consistent with competitiveinhibition at the NMDA receptor glycine-site mediating xenon neuroprotection against traumaticbrain injury. Xenon inhibits NMDA receptors and activates TREK-1 channels, while argon,krypton, neon and helium have no effect on these ion-channels.Conclusions. Xenon neuroprotection against traumatic brain injury can be reversed by elevatingthe glycine concentration, consistent with inhibition at the NMDA-receptor glycine site playing asignificant role in xenon neuroprotection. Argon and xenon do not act via the same mechanism.

  • Journal article
    Mohite PN, Zych B, Popov AF, Sabashnikov A, Saez DG, Patil NP, Amrani M, Bahrami T, DeRobertis F, Maunz O, Marczin N, Banner NR, Simon ARet al., 2013,

    CentriMag® short-term ventricular assist as a bridge to solution in patients with advanced heart failure: use beyond 30 days

    , EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, Vol: 44, Pages: E310-E315, ISSN: 1010-7940
  • Journal article
    Yip GM, Chen ZW, Edge CJ, Smith EH, Dickinson R, Hohenester E, Townsend RR, Fuchs K, Sieghart W, Evers AS, Franks NPet al., 2013,

    A propofol binding site on mammalian GABAA receptors identified by photolabeling

    , Nature Chemical Biology, Vol: 9, Pages: 715-720, ISSN: 1552-4469

    Propofol is the most important intravenous general anesthetic in current clinical use. It acts by potentiating GABAA (γ-aminobutyric acid type A) receptors, but where it binds to this receptor is not known and has been a matter of some debate. We synthesized a new propofol analog photolabeling reagent whose biological activity is very similar to that of propofol. We confirmed that this reagent labeled known propofol binding sites in human serum albumin that have been identified using X-ray crystallography. Using a combination of protiated and deuterated versions of the reagent to label mammalian receptors in intact membranes, we identified a new binding site for propofol in GABAA receptors consisting of both β3 homopentamers and α1β3 heteropentamers. The binding site is located within the β subunit at the interface between the transmembrane domains and the extracellular domain and lies close to known determinants of anesthetic sensitivity in the transmembrane segments TM1 and TM2.

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