The Experts below are selected from a list of 309174 Experts worldwide ranked by ideXlab platform
Shaf Keshavjee - One of the best experts on this subject based on the ideXlab platform.
-
Strategies to prolong homeostasis of Ex Vivo perfused lungs.
The Journal of thoracic and cardiovascular surgery, 2020Co-Authors: Mamoru Takahashi, Marcelo Cypel, Shaf Keshavjee, Manyin Chen, Mingyao Liu, Hei Yu Andrew Cheung, T. Watanabe, Ricardo Zamel, Yui Watanabe, Constantine HarmantasAbstract:Abstract Objectives Ex Vivo lung perfusion provides an innovative method to assess and repair donor lungs. The current Toronto Ex Vivo lung perfusion protocol can reliably and reproducibly preserve lungs for 12 hours. A longer Ex Vivo lung perfusion preservation time could enable the application of more advanced repair therapies and the rescue of more donor lungs for lung transplant. Our objective was to achieve stable 24-hour normothermic Ex Vivo lung perfusion. Methods We systematically Examined 3 modifications of Ex Vivo lung perfusion perfusate administration in a large animal 24-hour Ex Vivo lung perfusion model. Pig lungs were assigned to 4 groups (n = 5 per group): (1) control; (2) continuous replacement of Ex Vivo lung perfusion perfusate; (3) modified feed, which used a modified solution to maintain perfusate osmolality by adjusting glucose and sodium levels; and (4) total parenteral nutrition, in which we added parenteral nutrition to the perfusate. Results Only 1 lung in the control group completed 24-hour Ex Vivo lung perfusion. However, 24-hour perfusion was achieved in 4 lungs in the continuous replacement group, 3 lungs in the modified feed group, and 4 lungs in the total parenteral nutrition group. The total parenteral nutrition group achieved significantly longer stable perfusion time compared with control (P = .03). Lung function was significantly improved and inflammatory cytokine production was reduced in the continuous replacement and total parenteral nutrition groups compared with control. Conclusions Modifications of Ex Vivo lung perfusion perfusate toward achieving a stable homeostatic state can Extend perfusion time for up to 24 hours. Although these modifications allow for prolonged Ex Vivo lung perfusion, further research will be required to develop stable lung support beyond 24 hours.
-
Normothermic Ex Vivo Lung Perfusion in Clinical Lung Transplantation
Current Transplantation Reports, 2015Co-Authors: Jonathan C. Yeung, Shaf KeshavjeeAbstract:Normothermic Ex Vivo lung perfusion is a novel strategy of donor lung preservation that preserves the metabolic activity of the organ. There are therefore opportunities for further lung evaluation and therapeutic intervention during the Ex Vivo stage. We review our clinical Experience with this technique and offer perspectives for future development.
-
Ex-Vivo lung perfusion.
Transplant International, 2014Co-Authors: Dirk Van Raemdonck, Marcelo Cypel, Arne Neyrinck, Shaf KeshavjeeAbstract:Summary This review outlines the new and promising technique of Ex Vivo lung perfusion and its clinical potential to increase the number of transplantable lungs and to improve the early and late outcome after transplantation. The rationale, the Experimental background, the technique and protocols, and available devices for Ex Vivo lung perfusion are discussed. The current clinical Experience worldwide and ongoing clinical trials are reviewed.
-
Experience with the first 50 Ex Vivo lung perfusions in clinical transplantation.
The Journal of Thoracic and Cardiovascular Surgery, 2012Co-Authors: Marcelo Cypel, Jonathan C. Yeung, Tiago N. Machuca, Manyin Chen, Thomas K. Waddell, Lianne G. Singer, Kazuhiro Yasufuku, Marc De Perrot, Andrew Pierre, Shaf KeshavjeeAbstract:Objective Normothermic Ex Vivo lung perfusion is a novel method to evaluate and improve the function of injured donor lungs. We reviewed our Experience with 50 consecutive transplants after Ex Vivo lung perfusion. Methods A retrospective study using prospectively collected data was performed. High-risk brain death donor lungs (defined as Pa o 2 /F io 2 o 2 /F io 2 greater than 400 mm Hg during Ex Vivo lung perfusion were transplanted. The primary end point was the incidence of primary graft dysfunction grade 3 at 72 hours after transplantation. End points were compared with lung transplants not treated with Ex Vivo lung perfusion (controls). Results A total of 317 lung transplants were performed during the study period (39 months). Fifty-eight Ex Vivo lung perfusion procedures were performed, resulting in 50 transplants (86% use). Of these, 22 were from cardiac death donors and 28 were from brain death donors. The mean donor Pa o 2 /F io 2 was 334 mm Hg in the Ex Vivo lung perfusion group and 452 mm Hg in the control group ( P = .0001). The incidence of primary graft dysfunction grade 3 at 72 hours was 2% in the Ex Vivo lung perfusion group and 8.5% in the control group ( P = .14). One patient (2%) in the Ex Vivo lung perfusion group and 7 patients (2.7%) in the control group required Extracorporeal lung support for primary graft dysfunction ( P = 1.00). The median time to Extubation, intensive care unit stay, and hospital length of stay were 2, 4, and 20 days, respectively, in the Ex Vivo lung perfusion group and 2, 4, and 23 days, respectively, in the control group ( P > .05). Thirty-day mortality (4% in the Ex Vivo lung perfusion group and 3.5% in the control group, P = 1.00) and 1-year survival (87% in the Ex Vivo lung perfusion group and 86% in the control group, P = 1.00) were similar in both groups. Conclusions Transplantation of high-risk donor lungs after 4 to 6 hours of Ex Vivo lung perfusion is safe, and outcomes are similar to those of conventional transplants. Ex Vivo lung perfusion improved our center use of donor lungs, accounting for 20% of our current lung transplant activity.
-
Ex Vivo lung perfusion and reconditioning.
Multimedia Manual of Cardio-Thoracic Surgery, 2011Co-Authors: Jonathan C. Yeung, Marcelo Cypel, Ehab Massad, Shaf KeshavjeeAbstract:Normothermic Ex Vivo lung perfusion can act as a platform for the evaluation and repair of donor lungs. An acellular hyperosmolar solution is perfused anterograde through the donor lungs at 40% of the estimated cardiac output. Following oxygenation of the perfusate by the lung, it passes through a hollow fiber oxygenator supplied with a hypoxic gas mixture to remove oxygen and to maintain physiological carbon dioxide levels. Flow through a heat Exchanger to maintain normothermia and a leukocyte filter to remove demarginated leukocytes completes the circuit. Lung function can be measured by the difference in PO2 between the perfusate postlung and postmembrane and by physiological parameters. Utilization of this method of Ex Vivo donor lung evaluation should reduce concerns of primary graft dysfunction and increase utilization rates of donor lungs.
Marcelo Cypel - One of the best experts on this subject based on the ideXlab platform.
-
Strategies to prolong homeostasis of Ex Vivo perfused lungs.
The Journal of thoracic and cardiovascular surgery, 2020Co-Authors: Mamoru Takahashi, Marcelo Cypel, Shaf Keshavjee, Manyin Chen, Mingyao Liu, Hei Yu Andrew Cheung, T. Watanabe, Ricardo Zamel, Yui Watanabe, Constantine HarmantasAbstract:Abstract Objectives Ex Vivo lung perfusion provides an innovative method to assess and repair donor lungs. The current Toronto Ex Vivo lung perfusion protocol can reliably and reproducibly preserve lungs for 12 hours. A longer Ex Vivo lung perfusion preservation time could enable the application of more advanced repair therapies and the rescue of more donor lungs for lung transplant. Our objective was to achieve stable 24-hour normothermic Ex Vivo lung perfusion. Methods We systematically Examined 3 modifications of Ex Vivo lung perfusion perfusate administration in a large animal 24-hour Ex Vivo lung perfusion model. Pig lungs were assigned to 4 groups (n = 5 per group): (1) control; (2) continuous replacement of Ex Vivo lung perfusion perfusate; (3) modified feed, which used a modified solution to maintain perfusate osmolality by adjusting glucose and sodium levels; and (4) total parenteral nutrition, in which we added parenteral nutrition to the perfusate. Results Only 1 lung in the control group completed 24-hour Ex Vivo lung perfusion. However, 24-hour perfusion was achieved in 4 lungs in the continuous replacement group, 3 lungs in the modified feed group, and 4 lungs in the total parenteral nutrition group. The total parenteral nutrition group achieved significantly longer stable perfusion time compared with control (P = .03). Lung function was significantly improved and inflammatory cytokine production was reduced in the continuous replacement and total parenteral nutrition groups compared with control. Conclusions Modifications of Ex Vivo lung perfusion perfusate toward achieving a stable homeostatic state can Extend perfusion time for up to 24 hours. Although these modifications allow for prolonged Ex Vivo lung perfusion, further research will be required to develop stable lung support beyond 24 hours.
-
Ex Vivo lung perfusion
Clinical Transplantation, 2016Co-Authors: Jeremie Reeb, Marcelo CypelAbstract:Lung transplantation is an established life-saving therapy for patients with end-stage lung disease. Unfortunately, greater success in lung transplantation is hindered by a shortage of lung donors and the relatively poor early-, mid-, and long-term outcomes associated with severe primary graft dysfunction. Ex Vivo lung perfusion has emerged as a modern preservation technique that allows for a more accurate lung assessment and improvement in lung quality. This review outlines the: (i) rationale behind the method; (ii) techniques and protocols; (iii) Toronto Ex Vivo lung perfusion method; (iv) devices available; and (v) clinical Experience worldwide. We also highlight the potential of Ex Vivo lung perfusion in leading a new era of lung preservation.
-
Ex-Vivo lung perfusion.
Transplant International, 2014Co-Authors: Dirk Van Raemdonck, Marcelo Cypel, Arne Neyrinck, Shaf KeshavjeeAbstract:Summary This review outlines the new and promising technique of Ex Vivo lung perfusion and its clinical potential to increase the number of transplantable lungs and to improve the early and late outcome after transplantation. The rationale, the Experimental background, the technique and protocols, and available devices for Ex Vivo lung perfusion are discussed. The current clinical Experience worldwide and ongoing clinical trials are reviewed.
-
Ex Vivo lung perfusion (EVLP)
Current Respiratory Care Reports, 2013Co-Authors: Marcelo CypelAbstract:The number of patients listed for lung transplantation largely Exceeds the number of available transplantable organs because of both a shortage of organ donors and a low utilization rate of lungs from those donors. A novel strategy of donor lung management—Ex Vivo lung perfusion (EVLP)—that keeps the organ at physiological protective conditions has shown a great promise to increase lung utilization by re-evaluating, treating, and repairing donor lungs prior to transplantation. A clinical trial using EVLP has shown the method to be safe and to allow for reassessment and improvement in function from high-risk donor lungs from both brain death and cardiac death donors prior transplantation. When these lungs were transplanted, low rates of primary graft dysfunction were achieved, and the early outcomes were similar to those with conventionally selected and transplanted lungs. Pre-clinical studies have also shown a great potential of EVLP as a platform for the delivery of novel therapies to repair injured organs Ex Vivo, and thus further increase the donor lung utilization rate.
-
Physiologic assessment of the Ex Vivo donor lung for transplantation
The Journal of Heart and Lung Transplantation, 2012Co-Authors: Jonathan C. Yeung, Marcelo Cypel, Tiago N. Machuca, Terumoto Koike, Douglas J. Cook, R. Bonato, Manyin Chen, Masaaki Sato, Thomas K. Waddell, Mingyao LiuAbstract:Background The evaluation of donor lungs by normothermic Ex Vivo acellular perfusion has improved the safety of organ utilization. However, this strategy requires a critical re-evaluation of the parameters used to assess lungs during Ex Vivo perfusion compared with those traditionally used to evaluate the donor lung in Vivo. Using a porcine model, we studied the physiology of acellular lung perfusion with the aim of improving the accuracy of clinical Ex Vivo evaluation. Methods Porcine lungs after 10 hours of brain death and 24 hours of cold ischemia and uninjured control lungs were perfused for 12 hours and then transplanted. PaO 2 , compliance, airway pressure and pulmonary vascular resistance were measured. Ventilation with 100% nitrogen and addition of red blood cells to the perfusate were used to clarify the physiologic disparities between in Vivo blood perfusion and Ex Vivo acellular perfusion. Results During 12 hours of Ex Vivo perfusion, injured lungs developed edema with decreased compliance and increased airway pressure, but Ex Vivo PO 2 remained stable. After transplantation, injured lungs demonstrated high vascular resistance and poor PaO 2 . A reduced effect of shunt on Ex Vivo lung perfusion PO 2 was found to be attributable to the linearization of the relationship between oxygen content and PO 2 , which occurs with acellular perfusate. Conclusions Ex Vivo PO 2 may not be the first indication of lung injury and, taken alone, may be misleading in assessing the Ex Vivo lung. Thus, evaluation of other physiologic parameters takes on greater importance.
Jonathan C. Yeung - One of the best experts on this subject based on the ideXlab platform.
-
Normothermic Ex Vivo Lung Perfusion in Clinical Lung Transplantation
Current Transplantation Reports, 2015Co-Authors: Jonathan C. Yeung, Shaf KeshavjeeAbstract:Normothermic Ex Vivo lung perfusion is a novel strategy of donor lung preservation that preserves the metabolic activity of the organ. There are therefore opportunities for further lung evaluation and therapeutic intervention during the Ex Vivo stage. We review our clinical Experience with this technique and offer perspectives for future development.
-
Physiologic assessment of the Ex Vivo donor lung for transplantation
The Journal of Heart and Lung Transplantation, 2012Co-Authors: Jonathan C. Yeung, Marcelo Cypel, Tiago N. Machuca, Terumoto Koike, Douglas J. Cook, R. Bonato, Manyin Chen, Masaaki Sato, Thomas K. Waddell, Mingyao LiuAbstract:Background The evaluation of donor lungs by normothermic Ex Vivo acellular perfusion has improved the safety of organ utilization. However, this strategy requires a critical re-evaluation of the parameters used to assess lungs during Ex Vivo perfusion compared with those traditionally used to evaluate the donor lung in Vivo. Using a porcine model, we studied the physiology of acellular lung perfusion with the aim of improving the accuracy of clinical Ex Vivo evaluation. Methods Porcine lungs after 10 hours of brain death and 24 hours of cold ischemia and uninjured control lungs were perfused for 12 hours and then transplanted. PaO 2 , compliance, airway pressure and pulmonary vascular resistance were measured. Ventilation with 100% nitrogen and addition of red blood cells to the perfusate were used to clarify the physiologic disparities between in Vivo blood perfusion and Ex Vivo acellular perfusion. Results During 12 hours of Ex Vivo perfusion, injured lungs developed edema with decreased compliance and increased airway pressure, but Ex Vivo PO 2 remained stable. After transplantation, injured lungs demonstrated high vascular resistance and poor PaO 2 . A reduced effect of shunt on Ex Vivo lung perfusion PO 2 was found to be attributable to the linearization of the relationship between oxygen content and PO 2 , which occurs with acellular perfusate. Conclusions Ex Vivo PO 2 may not be the first indication of lung injury and, taken alone, may be misleading in assessing the Ex Vivo lung. Thus, evaluation of other physiologic parameters takes on greater importance.
-
Experience with the first 50 Ex Vivo lung perfusions in clinical transplantation.
The Journal of Thoracic and Cardiovascular Surgery, 2012Co-Authors: Marcelo Cypel, Jonathan C. Yeung, Tiago N. Machuca, Manyin Chen, Thomas K. Waddell, Lianne G. Singer, Kazuhiro Yasufuku, Marc De Perrot, Andrew Pierre, Shaf KeshavjeeAbstract:Objective Normothermic Ex Vivo lung perfusion is a novel method to evaluate and improve the function of injured donor lungs. We reviewed our Experience with 50 consecutive transplants after Ex Vivo lung perfusion. Methods A retrospective study using prospectively collected data was performed. High-risk brain death donor lungs (defined as Pa o 2 /F io 2 o 2 /F io 2 greater than 400 mm Hg during Ex Vivo lung perfusion were transplanted. The primary end point was the incidence of primary graft dysfunction grade 3 at 72 hours after transplantation. End points were compared with lung transplants not treated with Ex Vivo lung perfusion (controls). Results A total of 317 lung transplants were performed during the study period (39 months). Fifty-eight Ex Vivo lung perfusion procedures were performed, resulting in 50 transplants (86% use). Of these, 22 were from cardiac death donors and 28 were from brain death donors. The mean donor Pa o 2 /F io 2 was 334 mm Hg in the Ex Vivo lung perfusion group and 452 mm Hg in the control group ( P = .0001). The incidence of primary graft dysfunction grade 3 at 72 hours was 2% in the Ex Vivo lung perfusion group and 8.5% in the control group ( P = .14). One patient (2%) in the Ex Vivo lung perfusion group and 7 patients (2.7%) in the control group required Extracorporeal lung support for primary graft dysfunction ( P = 1.00). The median time to Extubation, intensive care unit stay, and hospital length of stay were 2, 4, and 20 days, respectively, in the Ex Vivo lung perfusion group and 2, 4, and 23 days, respectively, in the control group ( P > .05). Thirty-day mortality (4% in the Ex Vivo lung perfusion group and 3.5% in the control group, P = 1.00) and 1-year survival (87% in the Ex Vivo lung perfusion group and 86% in the control group, P = 1.00) were similar in both groups. Conclusions Transplantation of high-risk donor lungs after 4 to 6 hours of Ex Vivo lung perfusion is safe, and outcomes are similar to those of conventional transplants. Ex Vivo lung perfusion improved our center use of donor lungs, accounting for 20% of our current lung transplant activity.
-
Ex Vivo lung perfusion and reconditioning.
Multimedia Manual of Cardio-Thoracic Surgery, 2011Co-Authors: Jonathan C. Yeung, Marcelo Cypel, Ehab Massad, Shaf KeshavjeeAbstract:Normothermic Ex Vivo lung perfusion can act as a platform for the evaluation and repair of donor lungs. An acellular hyperosmolar solution is perfused anterograde through the donor lungs at 40% of the estimated cardiac output. Following oxygenation of the perfusate by the lung, it passes through a hollow fiber oxygenator supplied with a hypoxic gas mixture to remove oxygen and to maintain physiological carbon dioxide levels. Flow through a heat Exchanger to maintain normothermia and a leukocyte filter to remove demarginated leukocytes completes the circuit. Lung function can be measured by the difference in PO2 between the perfusate postlung and postmembrane and by physiological parameters. Utilization of this method of Ex Vivo donor lung evaluation should reduce concerns of primary graft dysfunction and increase utilization rates of donor lungs.
Nathanael Raschzok - One of the best experts on this subject based on the ideXlab platform.
-
Ex Vivo machine perfusion: current applications and future directions in liver transplantation
Langenbeck's Archives of Surgery, 2020Co-Authors: Julian Michelotto, Joseph M. G. V. Gassner, Simon Moosburner, Vanessa Muth, Madhukar S. Patel, Markus Selzner, Johann Pratschke, Igor M. Sauer, Nathanael RaschzokAbstract:Background Liver transplantation is the only curative treatment option for end-stage liver disease; however, its use remains limited due to a shortage of suitable organs. In recent years, Ex Vivo liver machine perfusion has been introduced to liver transplantation, as a means to Expand the donor organ pool. Purpose To present a systematic review of prospective clinical studies on Ex Vivo liver machine perfusion, in order to assess current applications and highlight future directions. Methods A systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed. Results Twenty-one articles on prospective clinical trials on Ex Vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, eleven on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of Ex Vivo liver machine perfusion in both standard and Expanded criteria donors. Currently, there are twelve studies enrolled in the clinicaltrials.gov registry, and these focus on use of Ex Vivo perfusion in Extended criteria donors and declined organs. Conclusion Ex Vivo liver machine perfusion seems to be a suitable strategy to Expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs.
-
Ex Vivo machine perfusion: current applications and future directions in liver transplantation.
Langenbeck's archives of surgery, 2020Co-Authors: Julian Michelotto, Joseph M. G. V. Gassner, Simon Moosburner, Vanessa Muth, Madhukar S. Patel, Markus Selzner, Johann Pratschke, Igor M. Sauer, Nathanael RaschzokAbstract:Liver transplantation is the only curative treatment option for end-stage liver disease; however, its use remains limited due to a shortage of suitable organs. In recent years, Ex Vivo liver machine perfusion has been introduced to liver transplantation, as a means to Expand the donor organ pool. To present a systematic review of prospective clinical studies on Ex Vivo liver machine perfusion, in order to assess current applications and highlight future directions. A systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed. Twenty-one articles on prospective clinical trials on Ex Vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, eleven on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of Ex Vivo liver machine perfusion in both standard and Expanded criteria donors. Currently, there are twelve studies enrolled in the clinicaltrials.gov registry, and these focus on use of Ex Vivo perfusion in Extended criteria donors and declined organs. Ex Vivo liver machine perfusion seems to be a suitable strategy to Expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs.
M. De Angel - One of the best experts on this subject based on the ideXlab platform.
-
Ex Vivo Expansion of umbilical cord blood
Cytotherapy, 2005Co-Authors: Simon N. Robinson, Marcos De Lima, Ting Niu, Hong Yang, John Mcmannis, S. Karandish, Tara Sadeghi, M. De AngelAbstract:The efficacy of cord blood (CB) transplantation is limited by the low cell dose available. Low cell doses at transplant are correlated with delayed engraftment, prolonged neutropenia and thrombocytopenia and elevated risk of graft failure. To potentially improve the efficacy of CB transplantation, approaches have been taken to increase the cell dose available. One approach is the transplantation of multiple cord units, another the use of Ex Vivo Expansion. Evidence for a functional and phenotypic heterogeneity Exists within the HSC population and one concern associated with Ex Vivo Expansion is that the Expansion of lower ‘quality’ hematopoietic progenitor cells (HPC) occurs at the Expense of higher ‘quality’ HPC, thereby impacting the reserve of the graft. There is evidence that this is a valid concern while other evidence suggests that higher quality HPC are preserved and not Exhausted. Currently, Ex Vivo Expansion processes include: (1) liquid Expansion: CD34+ or CD133+ cells are selected and cultured ...
-
Ex Vivo Expansion of umbilical cord blood
Cytotherapy, 2005Co-Authors: Simon N. Robinson, Marcos De Lima, Ting Niu, Hong Yang, John Mcmannis, S. Karandish, Tara Sadeghi, M. De AngelAbstract:The efficacy of cord blood (CB) transplantation is limited by the low cell dose available. Low cell doses at transplant are correlated with delayed engraftment, prolonged neutropenia and thrombocytopenia and elevated risk of graft failure. To potentially improve the efficacy of CB transplantation, approaches have been taken to increase the cell dose available. One approach is the transplantation of multiple cord units, another the use of Ex Vivo Expansion. Evidence for a functional and phenotypic heterogeneity Exists within the HSC population and one concern associated with Ex Vivo Expansion is that the Expansion of lower 'quality' hematopoietic progenitor cells (HPC) occurs at the Expense of higher 'quality' HPC, thereby impacting the reserve of the graft. There is evidence that this is a valid concern while other evidence suggests that higher quality HPC are preserved and not Exhausted. Currently, Ex Vivo Expansion processes include: (1) liquid Expansion: CD34+ or CD133+ cells are selected and cultured in medium containing factors targeting the proliferation and self-renewal of primitive hematopoietic progenitors; (2) co-culture Expansion: unmanipulated CB cells are cultured with stromal components of the hematopoietic microenvironment, specifically mesenchymal stem cells (MSC), in medium containing growth factors; and (3) continuous perfusion: CB HPC are cultured with growth factors in 'bioreactors' rather than in static cultures. These approaches are discussed. Ultimately, the goal of Ex Vivo Expansion is to increase the available dose of the CB cells responsible for successful engraftment, thereby reducing the time to engraftment and reducing the risk of graft failure.
