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Yuki, Koichi

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Yuki

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Koichi

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Yuki, Koichi
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Now showing 1 - 4 of 4
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    Pediatric Perioperative Stress Responses and Anesthesia
    (2017) Yuki, Koichi; Matsunami, Erika; Tazawa, Kazumasa; Wang, Wei; DiNardo, James; Koutsogiannaki, Sophia
    Summary Surgical stress responses cause an array of endocrinological, metabolic and immunological changes in patients. The landmark studies in the 1980s showed that adequate anesthesia dramatically improved the outcomes of pediatric surgical patients by attenuating stress hormonal responses, pointing out the harm of ‘inadequate’ anesthesia. Subsequent studies questioned the role of administering very high-dose anesthetics to further attenuate stress responses. Here we review the feature of surgical stress responses in pediatric patients including their difference from those in adult patients. Overall, pediatric patients show minimal or no resting energy expenditure change postoperatively. In adult patients, increased resting energy expenditure has been described. Pediatric patients demonstrated robust cortisol and catecholamine responses than adult patients. However, the duration of these surges is often short-lived. Systemic proinflammatory and anti-inflammatory cytokine levels have been measured. Pediatric patients showed less proinflammatory cytokine elevation, but had similar anti-antiinflamatory responses. We also review in detail the immunological changes in response to surgical stress. Based on our current knowledge, we attempted to understand the underlying mechanism how adequate anesthesia dramatically improved the outcome of patients. Although more work is needed to be done, understanding how pediatric patients respond to perioperative stress, and its mechanism and consequence will allow us to direct us into a better, perioperative management in this population.
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    An internal ligand-bound, metastable state of a leukocyte integrin, αXβ2
    (The Rockefeller University Press, 2013) Sen, Mehmet; Yuki, Koichi; Springer, Timothy
    How is massive conformational change in integrins achieved on a rapid timescale? We report crystal structures of a metastable, putative transition state of integrin αXβ2. The αXβ2 ectodomain is bent; however, a lattice contact stabilizes its ligand-binding αI domain in a high affinity, open conformation. Much of the αI α7 helix unwinds, loses contact with the αI domain, and reshapes to form an internal ligand that binds to the interface between the β propeller and βI domains. Lift-off of the αI domain above this platform enables a range of extensional and rotational motions without precedent in allosteric machines. Movements of secondary structure elements in the β2 βI domain occur in an order different than in β3 integrins, showing that integrin β subunits can be specialized to assume different intermediate states between closed and open. Mutations demonstrate that the structure trapped here is metastable and can enable rapid equilibration between bent and extended-open integrin conformations and up-regulation of leukocyte adhesiveness.
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    Stereoselectivity of Isoflurane in Adhesion Molecule Leukocyte Function-Associated Antigen-1
    (Public Library of Science, 2014) Bu, Weiming; Pereira, Luis; Eckenhoff, Roderic G.; Yuki, Koichi
    Background: Isoflurane in clinical use is a racemate of S- and R-isoflurane. Previous studies have demonstrated that the effects of S-isoflurane on relevant anesthetic targets might be modestly stronger (less than 2-fold) than R-isoflurane. The X-ray crystallographic structure of the immunological target, leukocyte function-associated antigen-1 (LFA-1) with racemic isoflurane suggested that only S-isoflurane bound specifically to this protein. If so, the use of specific isoflurane enantiomers may have advantage in the surgical settings where a wide range of inflammatory responses is expected to occur. Here, we have further tested the hypothesis that isoflurane enantioselectivity is apparent in solution binding and functional studies. Methods: First, binding of isoflurane enantiomers to LFA-1 was studied using 1-aminoanthracene (1-AMA) displacement assays. The binding site of each enantiomer on LFA-1 was studied using the docking program GLIDE. Functional studies employed the flow-cytometry based ICAM binding assay. Results: Both enantiomers decreased 1-AMA fluorescence signal (at 520 nm), indicating that both competed with 1-AMA and bound to the αL I domain. The docking simulation demonstrated that both enantiomers bound to the LFA-1 “lovastatin site.” ICAM binding assays showed that S-isoflurane inhibited more potently than R-isoflurane, consistent with the result of 1-AMA competition assay. Conclusions: In contrast with the x-ray crystallography, both enantiomers bound to and inhibited LFA-1. S-isoflurane showed slight preference over R-isoflurane.
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    Non-invasive Assessment of Cerebral Blood Flow and Oxygen Metabolism in Neonates during Hypothermic Cardiopulmonary Bypass: Feasibility and Clinical Implications
    (Nature Publishing Group, 2017) Ferradal, Silvina L.; Yuki, Koichi; Vyas, Rutvi; Ha, Christopher G.; Yi, Francesca; Stopp, Christian; Wypij, David; Cheng, Henry; Newburger, Jane; Kaza, Aditya; Franceschini, Maria; Kussman, Barry; Grant, P.
    The neonatal brain is extremely vulnerable to injury during periods of hypoxia and/or ischemia. Risk of brain injury is increased during neonatal cardiac surgery, where pre-existing hemodynamic instability and metabolic abnormalities are combined with long periods of low cerebral blood flow and/or circulatory arrest. Our understanding of events associated with cerebral hypoxia-ischemia during cardiopulmonary bypass (CPB) remains limited, largely due to inadequate tools to quantify cerebral oxygen delivery and consumption non-invasively and in real-time. This pilot study aims to evaluate cerebral blood flow (CBF) and oxygen metabolism (CMRO2) intraoperatively in neonates by combining two novel non-invasive optical techniques: frequency-domain near-infrared spectroscopy (FD-NIRS) and diffuse correlation spectroscopy (DCS). CBF and CMRO2 were quantified before, during and after deep hypothermic cardiopulmonary bypass (CPB) in nine neonates. Our results show significantly decreased CBF and CMRO2 during hypothermic CPB. More interestingly, a change of coupling between both variables is observed during deep hypothermic CPB in all subjects. Our results are consistent with previous studies using invasive techniques, supporting the concept of FD-NIRS/DCS as a promising technology to monitor cerebral physiology in neonates providing the potential for individual optimization of surgical management.