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  • 1
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    Cerebral mitochondrial dysfunction associated with deep hypothermic circulatory arrest in neonatal swine†
    Oxford University Press (OUP) ; 2018
    In:  European Journal of Cardio-Thoracic Surgery Vol. 54, No. 1 ( 2018-07-01), p. 162-168
    Details
    In: European Journal of Cardio-Thoracic Surgery, Oxford University Press (OUP), Vol. 54, No. 1 ( 2018-07-01), p. 162-168
    Abstract: Controversy remains regarding the use of deep hypothermic circulatory arrest (DHCA) in neonatal cardiac surgery. Alterations in cerebral mitochondrial bioenergetics are thought to contribute to ischaemia–reperfusion injury in DHCA. The purpose of this study was to compare cerebral mitochondrial bioenergetics for DHCA with deep hypothermic continuous perfusion using a neonatal swine model. METHODS Twenty-four piglets (mean weight 3.8 kg) were placed on cardiopulmonary bypass (CPB): 10 underwent 40-min DHCA, following cooling to 18°C, 10 underwent 40 min DHCA and 10 remained at deep hypothermia for 40 min; animals were subsequently rewarmed to normothermia. 4 remained on normothermic CPB throughout. Fresh brain tissue was harvested while on CPB and assessed for mitochondrial respiration and reactive oxygen species generation. Cerebral microdialysis samples were collected throughout the analysis. RESULTS DHCA animals had significantly decreased mitochondrial complex I respiration, maximal oxidative phosphorylation, respiratory control ratio and significantly increased mitochondrial reactive oxygen species (P  & lt; 0.05 for all). DHCA animals also had significantly increased cerebral microdialysis indicators of cerebral ischaemia (lactate/pyruvate ratio) and neuronal death (glycerol) during and after rewarming. CONCLUSIONS DHCA is associated with disruption of mitochondrial bioenergetics compared with deep hypothermic continuous perfusion. Preserving mitochondrial health may mitigate brain injury in cardiac surgical patients. Further studies are needed to better understand the mechanisms of neurological injury in neonatal cardiac surgery and correlate mitochondrial dysfunction with neurological outcomes.
    Type of Medium: Online Resource
    ISSN: 1010-7940 , 1873-734X
    URL: Article
    DOI: 10.1093/ejcts/ezx467
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 1500330-9
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  • 2
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    Comparison of three infant venous reservoirs with vacuum-assisted venous drainage during varying levels of cardiotomy suction
    SAGE Publications ; 2020
    In:  Perfusion Vol. 35, No. 1 ( 2020-01), p. 26-31
    Details
    In: Perfusion, SAGE Publications, Vol. 35, No. 1 ( 2020-01), p. 26-31
    Abstract: Vacuum-assisted venous drainage has gained widespread use within the pediatric perfusion community for use during cardiopulmonary bypass. It is questioned whether its efficiency may be compromised with application of excessive cardiotomy suction to the infant hard-shell venous reservoir. An in vitro simulation circuit was used to research this phenomenon. A comparison of three different infant hard-shell venous reservoirs also took place to determine if one reservoir type was more advantageous when handling cardiotomy suction. The reservoirs tested were the Maquet VHK 11000, Medtronic Affinity Pixie, and Terumo Capiox FX05. Methods: The in vitro simulation circuit consisted of a 1 L reservoir bag that was cannulated at one access point with an Edwards Lifesciences 10Fr aortic cannula and the other access area with an Edwards Lifesciences 10Fr right angle venous cannula and 12Fr right angle venous cannula that were joined together. Key points of measurement and response variables were the pressures on the connection of the venous cannulas, inlet of the venous reservoir, and flow through the venous line. Vacuum was applied and manipulated with a Maquet VAVD Controller to settings of −20 mmHg, −30 mmHg, –40 mmHg, −50 mmHg, and −60 mmHg. Cardiotomy suction was added at settings of 1 LPM, 2 LPM, 3 LPM, and 4 LPM. Values from each response variable were monitored and recorded. These data were utilized to compare the reservoirs with a random coefficient model for each response variable. Conclusions: There is an adverse effect of excessive cardiotomy suction on the efficacy of vacuum-assisted venous drainage in infant hard-shell venous reservoirs. There is no significant difference between the VHK 11000, Pixie, and FX05 regarding their ability to handle this occurrence. An important discovery was that the FX05 showed a greater transfer of vacuum to the venous cannulas and reservoir inlet.
    Type of Medium: Online Resource
    ISSN: 0267-6591 , 1477-111X
    URL: Article
    DOI: 10.1177/0267659119850344
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
    detail.hit.zdb_id: 2029611-3
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  • 3
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    Non-invasive optical neuromonitoring of the temperature-dependence of cerebral oxygen metabolism during deep hypothermic cardiopulmonary bypass in neonatal swine
    SAGE Publications ; 2020
    In:  Journal of Cerebral Blood Flow & Metabolism Vol. 40, No. 1 ( 2020-01), p. 187-203
    Details
    In: Journal of Cerebral Blood Flow & Metabolism, SAGE Publications, Vol. 40, No. 1 ( 2020-01), p. 187-203
    Abstract: Management of deep hypothermic (DH) cardiopulmonary bypass (CPB), a critical neuroprotective strategy, currently relies on non-invasive temperature to guide cerebral metabolic suppression during complex cardiac surgery in neonates. Considerable inter-subject variability in temperature response and residual metabolism may contribute to the persisting risk for postoperative neurological injury. To characterize and mitigate this variability, we assess the sufficiency of conventional nasopharyngeal temperature (NPT) guidance, and in the process, validate combined non-invasive frequency-domain diffuse optical spectroscopy (FD-DOS) and diffuse correlation spectroscopy (DCS) for direct measurement of cerebral metabolic rate of oxygen ( CMRO 2 ). During CPB, n = 8 neonatal swine underwent cooling from normothermia to 18℃, sustained DH perfusion for 40 min, and then rewarming to simulate cardiac surgery. Continuous non-invasive and invasive measurements of intracranial temperature (ICT) and CMRO 2 were acquired. Significant hysteresis ( p  〈  0.001) between cooling and rewarming periods in the NPT versus ICT and NPT versus CMRO 2 relationships were found. Resolution of this hysteresis in the ICT versus CMRO 2 relationship identified a crucial insufficiency of conventional NPT guidance. Non-invasive CMRO 2 temperature coefficients with respect to NPT ( Q 10  = 2.0) and ICT ( Q 10  = 2.5) are consistent with previous reports and provide further validation of FD-DOS/DCS CMRO 2 monitoring during DH CPB to optimize management.
    Type of Medium: Online Resource
    ISSN: 0271-678X , 1559-7016
    URL: Article
    DOI: 10.1177/0271678X18809828
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2020
    detail.hit.zdb_id: 2039456-1
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  • 4
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    The effect of polyunsaturated fats on bile acid metabolism and cholelithiasis in squirrel monkeys
    Elsevier BV ; 1978
    In:  Metabolism Vol. 27, No. 10 ( 1978-10), p. 1471-1484
    Details
    In: Metabolism, Elsevier BV, Vol. 27, No. 10 ( 1978-10), p. 1471-1484
    Type of Medium: Online Resource
    ISSN: 0026-0495
    URL: Article
    DOI: 10.1016/S0026-0495(78)80019-5
    Language: English
    Publisher: Elsevier BV
    Publication Date: 1978
    detail.hit.zdb_id: 2049062-8
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  • 5
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    Correlation of Cerebral Microdialysis with Non-Invasive Diffuse Optical Cerebral Hemodynamic Monitoring during Deep Hypothermic Cardiopulmonary Bypass
    MDPI AG ; 2022
    In:  Metabolites Vol. 12, No. 8 ( 2022-08-10), p. 737-
    Details
    In: Metabolites, MDPI AG, Vol. 12, No. 8 ( 2022-08-10), p. 737-
    Abstract: Neonates undergoing cardiac surgery involving aortic arch reconstruction are at an increased risk for hypoxic-ischemic brain injury. Deep hypothermia is utilized to help mitigate this risk when periods of circulatory arrest are needed for surgical repair. Here, we investigate correlations between non-invasive optical neuromonitoring of cerebral hemodynamics, which has recently shown promise for the prediction of postoperative white matter injury in this patient population, and invasive cerebral microdialysis biomarkers. We compared cerebral tissue oxygen saturation (StO2), relative total hemoglobin concentration (rTHC), and relative cerebral blood flow (rCBF) measured by optics against the microdialysis biomarkers of metabolic stress and injury (lactate–pyruvate ratio (LPR) and glycerol) in neonatal swine models of deep hypothermic cardiopulmonary bypass (DHCPB), selective antegrade cerebral perfusion (SACP), and deep hypothermic circulatory arrest (DHCA). All three optical parameters were negatively correlated with LPR and glycerol in DHCA animals. Elevation of LPR was found to precede the elevation of glycerol by 30–60 min. From these data, thresholds for the detection of hypoxic-ischemia-associated cerebral metabolic distress and neurological injury are suggested. In total, this work provides insight into the timing and mechanisms of neurological injury following hypoxic-ischemia and reports a quantitative relationship between hypoxic-ischemia severity and neurological injury that may inform DHCA management.
    Type of Medium: Online Resource
    ISSN: 2218-1989
    URL: Article
    DOI: 10.3390/metabo12080737
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2662251-8
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  • 6
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    Effects of circulatory arrest and cardiopulmonary bypass on cerebral autoregulation in neonatal swine
    Springer Science and Business Media LLC ; 2022
    In:  Pediatric Research Vol. 91, No. 6 ( 2022-05), p. 1374-1382
    Details
    In: Pediatric Research, Springer Science and Business Media LLC, Vol. 91, No. 6 ( 2022-05), p. 1374-1382
    Abstract: Cerebral autoregulation mechanisms help maintain adequate cerebral blood flow (CBF) despite changes in cerebral perfusion pressure. Impairment of cerebral autoregulation, during and after cardiopulmonary bypass (CPB), may increase risk of neurologic injury in neonates undergoing surgery. In this study, alterations of cerebral autoregulation were assessed in a neonatal swine model probing four perfusion strategies. Methods Neonatal swine ( n  = 25) were randomized to continuous deep hypothermic cardiopulmonary bypass (DH-CPB, n  = 7), deep hypothermic circulatory arrest (DHCA, n  = 7), selective cerebral perfusion (SCP, n  = 7) at deep hypothermia, or normothermic cardiopulmonary bypass (control, n  = 4). The correlation coefficient (LDx) between laser Doppler measurements of CBF and mean arterial blood pressure was computed at initiation and conclusion of CPB. Alterations in cerebral autoregulation were assessed by the change between initial and final LDx measurements. Results Cerebral autoregulation became more impaired (LDx increased) in piglets that underwent DH-CPB (initial LDx: median 0.15, IQR [0.03, 0.26] ; final: 0.45, [0.27, 0.74]; p  = 0.02). LDx was not altered in those undergoing DHCA ( p   〉  0.99) or SCP ( p  = 0.13). These differences were not explained by other risk factors. Conclusions In a validated swine model of cardiac surgery, DH-CPB had a significant effect on cerebral autoregulation, whereas DHCA and SCP did not. Impact Approximately half of the patients who survive neonatal heart surgery with cardiopulmonary bypass (CPB) experience neurodevelopmental delays. This preclinical investigation takes steps to elucidate and isolate potential perioperative risk factors of neurologic injury, such as impairment of cerebral autoregulation, associated with cardiac surgical procedures involving CPB. We demonstrate a method to characterize cerebral autoregulation during CPB pump flow changes in a neonatal swine model of cardiac surgery. Cerebral autoregulation was not altered in piglets that underwent deep hypothermic circulatory arrest (DHCA) or selective cerebral perfusion (SCP), but it was altered in piglets that underwent deep hypothermic CBP.
    Type of Medium: Online Resource
    ISSN: 0031-3998 , 1530-0447
    URL: Article
    DOI: 10.1038/s41390-021-01525-3
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2031217-9
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  • 7
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    Increased cerebral mitochondrial dysfunction and reactive oxygen species with cardiopulmonary bypass
    Oxford University Press (OUP) ; 2021
    In:  European Journal of Cardio-Thoracic Surgery Vol. 59, No. 6 ( 2021-06-14), p. 1256-1264
    Details
    In: European Journal of Cardio-Thoracic Surgery, Oxford University Press (OUP), Vol. 59, No. 6 ( 2021-06-14), p. 1256-1264
    Abstract: Neurodevelopmental injury after cardiac surgery using cardiopulmonary bypass (CPB) for congenital heart defects is common, but the mechanism behind this injury is unclear. This study examines the impact of CPB on cerebral mitochondrial reactive oxygen species (ROS) generation and mitochondrial bioenergetics. METHODS Twenty-three piglets (mean weight 4.2 ± 0.5 kg) were placed on CPB for either 1, 2, 3 or 4 h (n = 5 per group) or underwent anaesthesia without CPB (sham, n = 3). Microdialysis was used to measure metabolic markers of ischaemia. At the conclusion of CPB or 4 h of sham, brain tissue was harvested. Utilizing high-resolution respirometry, with simultaneous fluorometric analysis, mitochondrial respiration and ROS were measured. RESULTS There were no significant differences in markers of ischaemia between sham and experimental groups. Sham animals had significantly higher mitochondrial respiration than experimental animals, including maximal oxidative phosphorylation capacity of complex I (OXPHOSCI) (3.25 ± 0.18 vs 4-h CPB: 1.68 ± 0.10, P  & lt; 0.001) and maximal phosphorylating respiration capacity via convergent input through complexes I and II (OXPHOSCI+CII) (7.40 ± 0.24 vs 4-h CPB: 3.91 ± 0.20, P & lt; 0.0001). At 4-h, experimental animals had significantly higher ROS related to non-phosphorylating respiration through complexes I and II (ETSCI+CII) than shams (1.08 ± 0.13 vs 0.64 ± 0.04, P = 0.026). CONCLUSIONS Even in the absence of local markers of ischaemia, CPB is associated with decreased mitochondrial respiration relative to shams irrespective of duration. Exposure to 4 h of CPB resulted in a significant increase in cerebral mitochondrial ROS formation compared to shorter durations. Further study is needed to improve the understanding of cerebral mitochondrial health and its effects on the pathophysiology of neurological injury following exposure to CPB.
    Type of Medium: Online Resource
    ISSN: 1010-7940 , 1873-734X
    URL: Article
    DOI: 10.1093/ejcts/ezaa439
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 1500330-9
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  • 8
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    Mass Spectrometry-based Proteomics of Human Cannabinoid Receptor 2: Covalent Cysteine 6.47(257)-Ligand Interaction Affording Megagonist Receptor Activation
    American Chemical Society (ACS) ; 2011
    In:  Journal of Proteome Research Vol. 10, No. 10 ( 2011-10-07), p. 4789-4798
    Details
    In: Journal of Proteome Research, American Chemical Society (ACS), Vol. 10, No. 10 ( 2011-10-07), p. 4789-4798
    Type of Medium: Online Resource
    ISSN: 1535-3893 , 1535-3907
    URL: Article
    DOI: 10.1021/pr2005583
    Language: English
    Publisher: American Chemical Society (ACS)
    Publication Date: 2011
    detail.hit.zdb_id: 2065254-9
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  • 9
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    A single center’s conversion from roller pump to centrifugal pump technology in extracorporeal membrane oxygenation
    SAGE Publications ; 2016
    In:  Perfusion Vol. 31, No. 8 ( 2016-11), p. 662-667
    Details
    In: Perfusion, SAGE Publications, Vol. 31, No. 8 ( 2016-11), p. 662-667
    Abstract: Recent advances in blood pump technology have led to an increased use of centrifugal pumps for prolonged extracorporeal membrane oxygenation (ECMO). Data from the Extracorporeal Life Support Organization confirms that many institutions have converted to centrifugal pumps after prior experience with roller pump technology. Centrifugal pump technology is more compact and may generate less heat and hemolysis than a conventional roller pump. Based on the potential advantages of centrifugal pumps, a decision was made institution-wide to convert to centrifugal pump technology in pediatric implementation of ECMO. Based on limited prior experience with centrifugal pumps, a multidisciplinary approach was used to implement this new technology. The new centrifugal pump (Sorin Revolution, Arvada, CO) was intended for ECMO support in the cardiac intensive care unit (CICU), the pediatric intensive care unit (PICU) and the neonatal intensive care unit (NICU). Description: The perfusion team used their knowledge and expertise with centrifugal pumps to create the necessary teaching tools and interactive training sessions for the technical specialists who consisted primarily of registered nurses and respiratory therapists. The first phase consisted of educating all personnel involved in the care of the ECMO patient, followed by patient implementation in the CICU, followed by the PICU and NICU. Conclusion: The institution-wide conversion took several months to complete and was well received among all disciplines in the CICU and PICU. The NICU personnel did use the centrifugal pump circuit, but decided to revert back to using the roller pump technology. A systematic transition from roller pump to centrifugal pump technology with a multidisciplinary team can ensure a safe and successful implementation.
    Type of Medium: Online Resource
    ISSN: 0267-6591 , 1477-111X
    URL: Article
    DOI: 10.1177/0267659116651483
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
    detail.hit.zdb_id: 2029611-3
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  • 10
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    An in vitro comparison of the ability of three commonly used pediatric cardiopulmonary bypass circuits to filter gaseous microemboli
    SAGE Publications ; 2010
    In:  Perfusion Vol. 25, No. 4 ( 2010-07), p. 255-263
    Details
    In: Perfusion, SAGE Publications, Vol. 25, No. 4 ( 2010-07), p. 255-263
    Abstract: Background: The purpose of this study was to compare the ability of three commonly used pediatric cardiopulmonary bypass (CPB) circuits to filter gaseous microemboli (GME) in an in vitro model. Methods: Devices were tested at different levels of two specific independent variables: volume of air injected (1, 3, 5ml) and percentage of each oxygenator’s rated flow (50%, 75%, 100%, 125%). The air-handling ability of each CPB circuit was determined by the Emboli Detection and Classification Quantifier (Luna Innovations Inc., Roanoke,VA). Results: At all tested conditions, the FX-05 allowed a higher percentage of GME when compared to either one or both of the other two CPB circuits. When comparing oxygenators at similar absolute flow rates, the KIDS D100/D130 CPB circuit performed worse compared to the other two CPB circuits. C onclusions: The combination of the Baby RX-05 oxygenator and Capiox AF02 arterial line filter provides the highest level of protection from air emboli in an in vitro investigation.
    Type of Medium: Online Resource
    ISSN: 0267-6591 , 1477-111X
    URL: Article
    DOI: 10.1177/0267659110375489
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2010
    detail.hit.zdb_id: 2029611-3
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