13 results on '"Shuker, T."'
Search Results
2. An Ovine Model of Hemorrhagic Shock and Resuscitation, to Assess Recovery of Tissue Oxygen Delivery and Oxygen Debt, and Inform Patient Blood Management.
- Author
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Dyer, WB, Tung, J-P, Li Bassi, G, Wildi, K, Jung, J-S, Colombo, SM, Rozencwajg, S, Simonova, G, Chiaretti, S, Temple, FT, Ainola, C, Shuker, T, Palmieri, C, Shander, A, Suen, JY, Irving, DO, Fraser, JF, Dyer, WB, Tung, J-P, Li Bassi, G, Wildi, K, Jung, J-S, Colombo, SM, Rozencwajg, S, Simonova, G, Chiaretti, S, Temple, FT, Ainola, C, Shuker, T, Palmieri, C, Shander, A, Suen, JY, Irving, DO, and Fraser, JF
- Abstract
BACKGROUND: Aggressive fluid or blood component transfusion for severe hemorrhagic shock may restore macrocirculatory parameters, but not always improve microcirculatory perfusion and tissue oxygen delivery. We established an ovine model of hemorrhagic shock to systematically assess tissue oxygen delivery and repayment of oxygen debt; appropriate outcomes to guide Patient Blood Management. METHODS: Female Dorset-cross sheep were anesthetized, intubated, and subjected to comprehensive macrohemodynamic, regional tissue oxygen saturation (StO2), sublingual capillary imaging, and arterial lactate monitoring confirmed by invasive organ-specific microvascular perfusion, oxygen pressure, and lactate/pyruvate levels in brain, kidney, liver, and skeletal muscle. Shock was induced by stepwise withdrawal of venous blood until MAP was 30 mm Hg, mixed venous oxygen saturation (SvO2) < 60%, and arterial lactate >4 mM. Resuscitation with PlasmaLyte® was dosed to achieve MAP > 65 mm Hg. RESULTS: Hemorrhage impacted primary outcomes between baseline and development of shock: MAP 89 ± 5 to 31 ± 5 mm Hg (P < 0.01), SvO2 70 ± 7 to 23 ± 8% (P < 0.05), cerebral regional tissue StO2 77 ± 11 to 65 ± 9% (P < 0.01), peripheral muscle StO2 66 ± 8 to 16 ± 9% (P < 0.01), arterial lactate 1.5 ± 1.0 to 5.1 ± 0.8 mM (P < 0.01), and base excess 1.1 ± 2.2 to -3.6 ± 1.7 mM (P < 0.05). Invasive organ-specific monitoring confirmed reduced tissue oxygen delivery; oxygen tension decreased and lactate increased in all tissues, but moderately in brain. Blood volume replacement with PlasmaLyte® improved primary outcome measures toward baseline, confirmed by organ-specific measures, despite hemoglobin reduced from baseline 10.8 ± 1.2 to 5.9 ± 1.1 g/dL post-resuscitation (P < 0.01). CONCLUSION: Non-invasive measures of tissue oxygen delivery and oxygen debt repayment are suitable outcomes to inform Patient Blood Management of hemorrhagic shock, translatable for pre-clinical assessment of novel resuscitation s
- Published
- 2021
3. Donor Heart Preservation by Hypothermic Ex Vivo Perfusion - Improved Recipient Survival and Successful Prolongation of Ischemic Time
- Author
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Hoe, L.E. See, primary, Wildi, K., additional, Skeggs, K., additional, Bouquet, M., additional, Sato, K., additional, Jung, J., additional, Ainola, C., additional, Hyslop, K., additional, Heinsar, S., additional, Abbate, G., additional, Colombo, S.M., additional, Passmore, M., additional, Wood, E.S., additional, Wells, M., additional, Bartnikowski, N., additional, O'Neill, H., additional, Reid, J., additional, Shuker, T., additional, Haymet, A., additional, Livingstone, S., additional, Sato, N., additional, Obonyo, N., additional, James, L., additional, He, T., additional, McDonald, C., additional, Mullins, D., additional, Engkilde-Pedersen, S., additional, Diab, S., additional, Millar, J.E., additional, Malfertheiner, M., additional, Marshall, L., additional, Nair, L., additional, Rozencwajg, S., additional, Wang, X., additional, Shek, Y., additional, Platts, D., additional, Chan, J., additional, Boon, C., additional, Black, D., additional, Helms, L., additional, Bradbury, L., additional, Haqqani, H., additional, Molenaar, P., additional, Bassi, G. Li, additional, Suen, J., additional, McGiffin, D.C., additional, and Fraser, J.F., additional
- Published
- 2021
- Full Text
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4. Metabolic and mitochondrial alterations following brain death and heart transplantation
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Hoe, L. E.See, Wells, M. A., Bouquet, M., Hyslop, K., Passmore, M. R., Bartnikowski, N., Obonyo, N. G., Reid, J., O'Neill, H., Shuker, T., McDonald, C., Engkilde-Pedersen, S., Wildi, K., Ainola, C., Skeggs, K., Jung, J., Colombo, S., Sato, K., James, L., He, P., Wood, E. S., Heinser, S., Wang, X., Abbate, G., Livingstone, S., Haymet, A., Walweel, K., Mullins, D., Marasco, S., Diab, S., Tung, J., Molenaar, P., Bassi, G. Li, Suen, J. Y., McGiffin, D. C., Fraser, J. F., Hoe, L. E.See, Wells, M. A., Bouquet, M., Hyslop, K., Passmore, M. R., Bartnikowski, N., Obonyo, N. G., Reid, J., O'Neill, H., Shuker, T., McDonald, C., Engkilde-Pedersen, S., Wildi, K., Ainola, C., Skeggs, K., Jung, J., Colombo, S., Sato, K., James, L., He, P., Wood, E. S., Heinser, S., Wang, X., Abbate, G., Livingstone, S., Haymet, A., Walweel, K., Mullins, D., Marasco, S., Diab, S., Tung, J., Molenaar, P., Bassi, G. Li, Suen, J. Y., McGiffin, D. C., and Fraser, J. F.
- Abstract
PURPOSE: Brain death (BD) causes metabolic and energetic imbalances leading to cardiac dysfunction, and predisposes the donor heart to further injury following heart transplantation (HTx). The metabolic mechanisms required for myocardial energy production during BD and subsequent HTx are poorly understood. Our aim was to determine the myocardial metabolic profile and mitochondrial function following donor BD and HTx. METHODS: Donor BD in sheep was induced by inflation of a catheter placed through the skull (catheter placement, but no inflation for SHAM), followed by 24 hrs monitoring, and heart procurement (n=6/group, BD vs. SHAM). Additional donor hearts exposed to BD/SHAM were flushed with cold St Thomas cardioplegia, and stored via cold static storage (CSS) for ∼2 hrs. Following standard orthotopic HTx, recipients were weaned off bypass and monitored for ≤6 hrs prior to heart procurement (n=4/group, BD-Tx vs. Sh-Tx). Cardiac mitochondrial function was assessed using high resolution respirometry. Metabolic profiles were determined in hearts using metabolomics. Cardiac mitochondrial function was also determined in two sheep that underwent HTx following BD and 8 hr hypothermic ex vivo perfusion (HEVP) preservation. RESULTS: BD caused significant right ventricular (RV) mitochondrial uncoupling (vs. SHAM). HTx following CSS also impaired RV mitochondrial function, with these effects more pronounced in hearts exposed to both donor BD and HTx. Early findings show that HEVP improved cardiac mitochondrial function post-HTx (vs. CSS). Metabolically, BD increased myocardial amino-acid utilisation and accumulation of glucose metabolites. Post-HTx, particularly in those exposed to donor BD, there was a significant decrease in metabolites involved in mitochondrial respiration (eg. NAD, Acetyl-CoA) and accumulation of fatty acids and xanthine (purine breakdown). CONCLUSION: BD appears to trigger cardiac mitochon
- Published
- 2020
5. Metabolic and Mitochondrial Alterations Following Brain Death and Heart Transplantation
- Author
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Hoe, L.E. See, primary, Wells, M.A., additional, Bouquet, M., additional, Hyslop, K., additional, Passmore, M.R., additional, Bartnikowski, N., additional, Obonyo, N.G., additional, Reid, J., additional, O'Neill, H., additional, Shuker, T., additional, McDonald, C., additional, Engkilde-Pedersen, S., additional, Wildi, K., additional, Ainola, C., additional, Skeggs, K., additional, Jung, J., additional, Colombo, S., additional, Sato, K., additional, James, L., additional, He, P., additional, Wood, E.S., additional, Heinser, S., additional, Wang, X., additional, Abbate, G., additional, Livingstone, S., additional, Haymet, A., additional, Walweel, K., additional, Mullins, D., additional, Marasco, S., additional, Diab, S., additional, Tung, J., additional, Molenaar, P., additional, Bassi, G. Li, additional, Suen, J.Y., additional, McGiffin, D.C., additional, and Fraser, J.F., additional
- Published
- 2020
- Full Text
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6. 120 Hypothermic Ex Vivo Perfusion of Brain Dead Donor Hearts Improves Survival, Systemic Inflammation and Cardiac Function Following Heart Transplantation
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See Hoe, L., primary, McGiffin, D., additional, Wildi, K., additional, Obonyo, N., additional, Bouquet, M., additional, Wells, M., additional, Skeggs, K., additional, McDonald, C., additional, Engkilde-Pedersen, S., additional, Bartnikowski, N., additional, Colombo, S., additional, Ainola, C., additional, Passmore, M., additional, Hyslop, K., additional, Wood, E., additional, Shuker, T., additional, Sato, K., additional, Jung, J., additional, Heinser, S., additional, James, L., additional, Reid, J., additional, O'Neill, H., additional, Livingstone, S., additional, Abbate, G., additional, He, P., additional, Sato, N., additional, Boon, C., additional, Black, D., additional, Haymet, A., additional, Mullins, D., additional, Marasco, S., additional, Chan, W., additional, Chan, J., additional, Platts, D., additional, Diab, S., additional, Millar, J., additional, Li Bassi, G., additional, Suen, J., additional, and Fraser, J., additional
- Published
- 2020
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7. 121 Hypothermic Ex Vivo Perfusion Preserves Post-Transplant Donor Cardiac Function
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Sato, K., primary, See Hoe, L., additional, Obonyo, N., additional, Wildi, K., additional, Colombo, S., additional, Bouquet, M., additional, Passmore, M., additional, Bartnikowski, N., additional, Wells, M., additional, Skeggs, K., additional, McDonald, C., additional, Hyslop, K., additional, Wood, E., additional, Heinser, S., additional, Ainola, C., additional, Jung, J., additional, James, L., additional, Abbate, G., additional, Haymet, A., additional, Engkilde-Pedersen, S., additional, Reid, J., additional, O'Neill, H., additional, Shuker, T., additional, He, P., additional, Sato, N., additional, Diab, S., additional, Mullins, D., additional, Livingstone, S., additional, Wang, X., additional, Rozencwajg, S., additional, Malfertheiner, M., additional, Platts, D., additional, Chan, J., additional, Li Bassi, G., additional, Suen, J., additional, McGiffin, D., additional, and Fraser, J., additional
- Published
- 2020
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8. Characterisation of Cardiac Neurohormonal and Inflammatory Changes Induced by Brain Death in a Novel Ovine Heart Transplant Model
- Author
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Hoe, L. See, primary, Shuker, T., additional, Bartnikowski, N., additional, Passmore, M., additional, Bouquet, M., additional, Obonyo, N., additional, Engkilde-Pedersen, S., additional, McDonald, C., additional, Wells, M., additional, Boon, A., additional, Hyslop, K., additional, James, L., additional, Wildi, K., additional, Cullen, L., additional, Bassi, G. Li, additional, Suen, J., additional, McGiffin, D., additional, and Fraser, J., additional
- Published
- 2019
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9. Comprehensive review of deep learning in orthopaedics: Applications, challenges, trustworthiness, and fusion.
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Alzubaidi L, Al-Dulaimi K, Salhi A, Alammar Z, Fadhel MA, Albahri AS, Alamoodi AH, Albahri OS, Hasan AF, Bai J, Gilliland L, Peng J, Branni M, Shuker T, Cutbush K, Santamaría J, Moreira C, Ouyang C, Duan Y, Manoufali M, Jomaa M, Gupta A, Abbosh A, and Gu Y
- Subjects
- Humans, Deep Learning, Orthopedics methods
- Abstract
Deep learning (DL) in orthopaedics has gained significant attention in recent years. Previous studies have shown that DL can be applied to a wide variety of orthopaedic tasks, including fracture detection, bone tumour diagnosis, implant recognition, and evaluation of osteoarthritis severity. The utilisation of DL is expected to increase, owing to its ability to present accurate diagnoses more efficiently than traditional methods in many scenarios. This reduces the time and cost of diagnosis for patients and orthopaedic surgeons. To our knowledge, no exclusive study has comprehensively reviewed all aspects of DL currently used in orthopaedic practice. This review addresses this knowledge gap using articles from Science Direct, Scopus, IEEE Xplore, and Web of Science between 2017 and 2023. The authors begin with the motivation for using DL in orthopaedics, including its ability to enhance diagnosis and treatment planning. The review then covers various applications of DL in orthopaedics, including fracture detection, detection of supraspinatus tears using MRI, osteoarthritis, prediction of types of arthroplasty implants, bone age assessment, and detection of joint-specific soft tissue disease. We also examine the challenges for implementing DL in orthopaedics, including the scarcity of data to train DL and the lack of interpretability, as well as possible solutions to these common pitfalls. Our work highlights the requirements to achieve trustworthiness in the outcomes generated by DL, including the need for accuracy, explainability, and fairness in the DL models. We pay particular attention to fusion techniques as one of the ways to increase trustworthiness, which have also been used to address the common multimodality in orthopaedics. Finally, we have reviewed the approval requirements set forth by the US Food and Drug Administration to enable the use of DL applications. As such, we aim to have this review function as a guide for researchers to develop a reliable DL application for orthopaedic tasks from scratch for use in the market., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)
- Published
- 2024
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10. Donor heart ischemic time can be extended beyond 9 hours using hypothermic machine perfusion in sheep.
- Author
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See Hoe LE, Li Bassi G, Wildi K, Passmore MR, Bouquet M, Sato K, Heinsar S, Ainola C, Bartnikowski N, Wilson ES, Hyslop K, Skeggs K, Obonyo NG, Shuker T, Bradbury L, Palmieri C, Engkilde-Pedersen S, McDonald C, Colombo SM, Wells MA, Reid JD, O'Neill H, Livingstone S, Abbate G, Haymet A, Jung JS, Sato N, James L, He T, White N, Redd MA, Millar JE, Malfertheiner MV, Molenaar P, Platts D, Chan J, Suen JY, McGiffin DC, and Fraser JF
- Subjects
- Animals, Sheep, Humans, Organ Preservation methods, Tissue Donors, Perfusion methods, Heart, Heart Transplantation
- Abstract
Background: The global shortage of donor hearts available for transplantation is a major problem for the treatment of end-stage heart failure. The ischemic time for donor hearts using traditional preservation by standard static cold storage (SCS) is limited to approximately 4 hours, beyond which the risk for primary graft dysfunction (PGD) significantly increases. Hypothermic machine perfusion (HMP) of donor hearts has been proposed to safely extend ischemic time without increasing the risk of PGD., Methods: Using our sheep model of 24 hours brain death (BD) followed by orthotopic heart transplantation (HTx), we examined post-transplant outcomes in recipients following donor heart preservation by HMP for 8 hours, compared to donor heart preservation for 2 hours by either SCS or HMP., Results: Following HTx, all HMP recipients (both 2 hours and 8 hours groups) survived to the end of the study (6 hours after transplantation and successful weaning from cardiopulmonary bypass), required less vasoactive support for hemodynamic stability, and exhibited superior metabolic, fluid status and inflammatory profiles compared to SCS recipients. Contractile function and cardiac damage (troponin I release and histological assessment) was comparable between groups., Conclusions: Overall, compared to current clinical SCS, recipient outcomes following transplantation are not adversely impacted by extending HMP to 8 hours. These results have important implications for clinical transplantation where longer ischemic times may be required (e.g., complex surgical cases, transport across long distances). Additionally, HMP may allow safe preservation of "marginal" donor hearts that are more susceptible to myocardial injury and facilitate increased utilization of these hearts for transplantation., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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11. A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death.
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See Hoe LE, Wildi K, Obonyo NG, Bartnikowski N, McDonald C, Sato K, Heinsar S, Engkilde-Pedersen S, Diab S, Passmore MR, Wells MA, Boon AC, Esguerra A, Platts DG, James L, Bouquet M, Hyslop K, Shuker T, Ainola C, Colombo SM, Wilson ES, Millar JE, Malfertheiner MV, Reid JD, O'Neill H, Livingstone S, Abbate G, Sato N, He T, von Bahr V, Rozencwajg S, Byrne L, Pimenta LP, Marshall L, Nair L, Tung JP, Chan J, Haqqani H, Molenaar P, Li Bassi G, Suen JY, McGiffin DC, and Fraser JF
- Abstract
Background: Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD., Methods: BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB), and monitored for 6 h. Donor and recipient blood were assayed for inflammatory and cardiac injury markers, and cardiac function was assessed using echocardiography. Repeated measurements between the two different groups during the study observation period were assessed by mixed ANOVA for repeated measures., Results: Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure, p = 0.09), systemic inflammation (IL-6 - p = 0.025, IL-8 - p = 0.002) and cardiac injury (cardiac troponin I, p = 0.048), requiring vasopressor support (vasopressor dependency index, VDI, p = 0.023), with normalisation of biomarkers and physiology over 24 h. All hearts were weaned from CPB and monitored for 6 h post-HTx, except one (sham) recipient that died 2 h post-HTx. Hemodynamic (VDI - p = 0.592, heart rate - p = 0.747) and metabolic (blood lactate, p = 0.546) parameters post-HTx were comparable between groups, despite the observed physiological perturbations that occurred during donor BSD. All p values denote interaction among groups and time in the ANOVA for repeated measures., Conclusions: We have successfully developed an ovine HTx model following 24 h of donor BSD. After 6 h of critical care management post-HTx, there were no differences between groups, despite evident hemodynamic perturbations, systemic inflammation, and cardiac injury observed during donor BSD. This preclinical model provides a platform for critical assessment of injury development pre- and post-HTx, and novel therapeutic evaluation., (© 2021. The Author(s).)
- Published
- 2021
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12. An Ovine Model of Hemorrhagic Shock and Resuscitation, to Assess Recovery of Tissue Oxygen Delivery and Oxygen Debt, and Inform Patient Blood Management.
- Author
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Dyer WB, Tung JP, Li Bassi G, Wildi K, Jung JS, Colombo SM, Rozencwajg S, Simonova G, Chiaretti S, Temple FT, Ainola C, Shuker T, Palmieri C, Shander A, Suen JY, Irving DO, and Fraser JF
- Subjects
- Animals, Blood Transfusion, Disease Models, Animal, Female, Humans, Middle Aged, Sheep, Oxygen metabolism, Oxygen Consumption, Recovery of Function, Resuscitation, Shock, Hemorrhagic therapy
- Abstract
Background: Aggressive fluid or blood component transfusion for severe hemorrhagic shock may restore macrocirculatory parameters, but not always improve microcirculatory perfusion and tissue oxygen delivery. We established an ovine model of hemorrhagic shock to systematically assess tissue oxygen delivery and repayment of oxygen debt; appropriate outcomes to guide Patient Blood Management., Methods: Female Dorset-cross sheep were anesthetized, intubated, and subjected to comprehensive macrohemodynamic, regional tissue oxygen saturation (StO2), sublingual capillary imaging, and arterial lactate monitoring confirmed by invasive organ-specific microvascular perfusion, oxygen pressure, and lactate/pyruvate levels in brain, kidney, liver, and skeletal muscle. Shock was induced by stepwise withdrawal of venous blood until MAP was 30 mm Hg, mixed venous oxygen saturation (SvO2) < 60%, and arterial lactate >4 mM. Resuscitation with PlasmaLyte® was dosed to achieve MAP > 65 mm Hg., Results: Hemorrhage impacted primary outcomes between baseline and development of shock: MAP 89 ± 5 to 31 ± 5 mm Hg (P < 0.01), SvO2 70 ± 7 to 23 ± 8% (P < 0.05), cerebral regional tissue StO2 77 ± 11 to 65 ± 9% (P < 0.01), peripheral muscle StO2 66 ± 8 to 16 ± 9% (P < 0.01), arterial lactate 1.5 ± 1.0 to 5.1 ± 0.8 mM (P < 0.01), and base excess 1.1 ± 2.2 to -3.6 ± 1.7 mM (P < 0.05). Invasive organ-specific monitoring confirmed reduced tissue oxygen delivery; oxygen tension decreased and lactate increased in all tissues, but moderately in brain. Blood volume replacement with PlasmaLyte® improved primary outcome measures toward baseline, confirmed by organ-specific measures, despite hemoglobin reduced from baseline 10.8 ± 1.2 to 5.9 ± 1.1 g/dL post-resuscitation (P < 0.01)., Conclusion: Non-invasive measures of tissue oxygen delivery and oxygen debt repayment are suitable outcomes to inform Patient Blood Management of hemorrhagic shock, translatable for pre-clinical assessment of novel resuscitation strategies., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by the Shock Society.)
- Published
- 2021
- Full Text
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13. Heart Transplantation From Brain Dead Donors: A Systematic Review of Animal Models.
- Author
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See Hoe LE, Wells MA, Bartnikowski N, Obonyo NG, Millar JE, Khoo A, Ki KK, Shuker T, Ferraioli A, Colombo SM, Chan W, McGiffin DC, Suen JY, and Fraser JF
- Subjects
- Animals, Heart Failure physiopathology, Hemodynamics, Humans, Models, Animal, Primary Graft Dysfunction physiopathology, Species Specificity, Ventricular Function, Left, Ventricular Function, Right, Brain Death, Heart Failure surgery, Heart Transplantation adverse effects, Primary Graft Dysfunction etiology, Tissue Donors
- Abstract
Despite advances in mechanical circulatory devices and pharmacologic therapies, heart transplantation (HTx) is the definitive and most effective therapy for an important proportion of qualifying patients with end-stage heart failure. However, the demand for donor hearts significantly outweighs the supply. Hearts are sourced from donors following brain death, which exposes donor hearts to substantial pathophysiological perturbations that can influence heart transplant success and recipient survival. Although significant advances in recipient selection, donor and HTx recipient management, immunosuppression, and pretransplant mechanical circulatory support have been achieved, primary graft dysfunction after cardiac transplantation continues to be an important cause of morbidity and mortality. Animal models, when appropriate, can guide/inform medical practice, and fill gaps in knowledge that are unattainable in clinical settings. Consequently, we performed a systematic review of existing animal models that incorporate donor brain death and subsequent HTx and assessed studies for scientific rigor and clinical relevance. Following literature screening via the U.S National Library of Medicine bibliographic database (MEDLINE) and Embase, 29 studies were assessed. Analysis of included studies identified marked heterogeneity in animal models of donor brain death coupled to HTx, with few research groups worldwide identified as utilizing these models. General reporting of important determinants of heart transplant success was mixed, and assessment of posttransplant cardiac function was limited to an invasive technique (pressure-volume analysis), which is limitedly applied in clinical settings. This review highlights translational challenges between available animal models and clinical heart transplant settings that are potentially hindering advancement of this field of investigation.
- Published
- 2020
- Full Text
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