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Normothermic Ex vivo perfusion

Jonathan C Yeung, Ricardo Zamel, William Klement, Xiao-Hui Bai, Tiago N Machuca, Thomas K Waddell, Mingyao Liu, Marcelo Cypel, Shaf Keshavjee
We and others have demonstrated that acellular normothermic ex vivo lung perfusion of high-risk donor lungs can result in post-transplant outcomes equivalent to that of contemporaneous lung transplantation using standard donor lungs. However, the mechanism of this effect remains unclear. Given the restoration of cellular metabolic activity during normothermic perfusion, one possibility is that of lung healing via natural innate recovery mechanisms. We explored this by examining the gene expression changes occurring in human lungs during ex vivo lung perfusion...
February 15, 2018: American Journal of Transplantation
Federica Rigo, Nicola De Stefano, Victor Navarro-Tableros, Ezio David, Giorgia Rizza, Giorgia Catalano, Nicholas Gilbo, Francesca Maione, Federica Gonella, Dorotea Roggio, Silvia Martini, Damiano Patrono, Mauro Salizzoni, Giovanni Camussi, Renato Romagnoli
BACKGROUND: The gold standard for organ preservation before transplantation is static cold storage, which is unable to fully protect suboptimal livers from ischemia/reperfusion injury. An emerging alternative is normothermic machine perfusion (NMP), which permits organ reconditioning. Here, we aimed to explore the feasibility of a pharmacological intervention on isolated rat livers by using a combination of NMP and human liver stem cells-derived extracellular vesicles (HLSC-EV). METHODS: We established an ex vivo murine model of NMP capable to maintain liver function despite an ongoing hypoxic injury induced by hemodilution...
February 9, 2018: Transplantation
Jaskiran K Sandha, Christopher W White, Alison Müller, Emma Avery, James Thliveris, Ian M C Dixon, Rakesh C Arora, Ganghong Tian, Larry V Hryshko, Jayan Nagendran, Darren H Freed
BACKGROUND: Normothermic ex vivo heart perfusion (EVHP) has been shown to improve the preservation of hearts donated after circulatory arrest and facilitate clinical successful transplantation. Steroids are added to the perfusate solution in current clinical EVHP protocols; however, the impact of this approach on donor heart preservation has not been previously investigated. We sought to determine the impact of steroids on the inflammatory response and development of myocardial edema during EVHP...
January 27, 2018: Annals of Thoracic Surgery
B L Phillips, P Chandak, R Uwechue, C van Nispen Tot Pannerden, C Hemsley, C J Callaghan
No abstract text is available yet for this article.
January 3, 2018: Transplantation
Michael K Hsin, Ricardo Zamel, Marcelo Cypel, David Wishart, Beomsoo Han, Shaf Keshavjee, Mingyao Liu
OBJECTIVE: To identify potential biomarkers during ex vivo lung perfusion (EVLP) using metabolomics approach. SUMMARY BACKGROUND DATA: EVLP increases the number of usable donor lungs for lung transplantation (LTx) by physiologic assessment of explanted marginal lungs. The underlying paradigm of EVLP is the normothermic perfusion of cadaveric lungs previously flushed and stored in hypothermic preservation fluid, which allows the resumption of active cellular metabolism and respiratory function...
January 2018: Annals of Surgery
S A Hosgood, E Thompson, T Moore, C H Wilson, M L Nicholson
BACKGROUND: A significant proportion of donation after circulatory death (DCD) kidneys are declined for transplantation because of concerns over their quality. Ex vivo normothermic machine perfusion (NMP) provides a unique opportunity to assess the quality of a kidney and determine its suitability for transplantation. METHODS: In phase 1 of this study, declined human DCD kidneys underwent NMP assessment for 60 min. Kidneys were graded 1-5 using a quality assessment score (QAS) based on macroscopic perfusion, renal blood flow and urine output during NMP...
March 2018: British Journal of Surgery
Juan Echeverri, Nicolas Goldaracena, Johan Moritz Kaths, Ivan Linares, Roizar Roizales, Dagmar Kollmann, Matyas Hamar, Peter Urbanellis, Sujani Ganesh, Oyedele A Adeyi, Mahmood Tazari, Markus Selzner, Nazia Selzner
BACKGROUND: The optimal vasodilator to avoid hepatic artery (HA) vasospasm during normothermic ex vivo liver perfusion (NEVLP) is yet to be determined. We compared safety and efficacy of BQ123 (endothelin1 antagonist), Epoprostenol (prostacyclin analogue), and Verapamil (calcium channel antagonist). METHODS: Livers from porcine heart beating donors were perfused for 3 hours and transplanted into recipient pigs. Four groups were compared: Group 1: livers perfused with a dose of 1...
November 20, 2017: Transplantation
Gregory T Tietjen, Sarah A Hosgood, Jenna DiRito, Jiajia Cui, Deeksha Deep, Eric Song, Jan R Kraehling, Alexandra S Piotrowski-Daspit, Nancy C Kirkiles-Smith, Rafia Al-Lamki, Sathia Thiru, J Andrew Bradley, Kourosh Saeb-Parsy, John R Bradley, Michael L Nicholson, W Mark Saltzman, Jordan S Pober
Ex vivo normothermic machine perfusion (NMP) is a new clinical strategy to assess and resuscitate organs likely to be declined for transplantation, thereby increasing the number of viable organs available. Short periods of NMP provide a window of opportunity to deliver therapeutics directly to the organ and, in particular, to the vascular endothelial cells (ECs) that constitute the first point of contact with the recipient's immune system. ECs are the primary targets of both ischemia-reperfusion injury and damage from preformed antidonor antibodies, and reduction of perioperative EC injury could have long-term benefits by reducing the intensity of the host's alloimmune response...
November 29, 2017: Science Translational Medicine
Huiqing Lin, Manyin Chen, Feng Tian, Jussi Tikkanen, Lei Ding, Hei Yu Andrew Cheung, Daisuke Nakajima, Zhe Wang, Andrea Mariscal, David Hwang, Marcelo Cypel, Shaf Keshavjee, Mingyao Liu
BACKGROUND: Ex-vivo lung perfusion (EVLP), a technique for donor lung assessment, also represents a platform for donor lung repair and immunomodulation. α1 -Anti-trypsin (A1AT), a medication used to treat emphysema in A1AT-deficient patients, has anti-inflammatory properties and has been shown to attenuate ischemia-reperfusion injury in rat and pig lung transplants. The objective of this study was to determine whether administration of A1AT during EVLP can improve donor lung quality after prolonged hypothermic preservation...
October 2, 2017: Journal of Heart and Lung Transplantation
Nader S Aboelnazar, Sayed Himmat, Sanaz Hatami, Christopher W White, Mohamad S Burhani, Peter Dromparis, Nobutoshi Matsumura, Ganghong Tian, Jason R B Dyck, Michael Mengel, Darren H Freed, Jayan Nagendran
BACKGROUND: Normothermic ex-vivo lung perfusion (EVLP) using positive pressure ventilation (PPV) and both acellular and red blood cell (RBC)-based perfusate solutions have increased the rate of donor organ utilization. We sought to determine whether a negative pressure ventilation (NPV) strategy would improve donor lung assessment during EVLP. METHODS: Thirty-two pig lungs were perfused ex vivo for 12 hours in a normothermic state, and were allocated equally to 4 groups according to the mode of ventilation (positive pressure ventilation [PPV] vs NPV) and perfusate composition (acellular vs RBC)...
September 14, 2017: Journal of Heart and Lung Transplantation
Sarah A Hosgood, Tom Moore, Theresa Kleverlaan, Tom Adams, Michael L Nicholson
BACKGROUND: Ex-vivo normothermic perfusion strategies are a promising new instrument in organ transplantation. The perfusion conditions are designed to be protective however the artificial environment can induce a local inflammatory response. The aim of this study was to determine the effect of incorporating a Cytosorb adsorber into an isolated kidney perfusion system. METHODS: Porcine kidneys were subjected to 22 h of cold ischaemia then reperfused for 6 h on an ex vivo reperfusion circuit...
October 25, 2017: Journal of Translational Medicine
Xiaoshun He, Fei Ji, Zhiheng Zhang, Yunhua Tang, Lu Yang, Shanzhou Huang, Wenwen Li, Qiao Su, Wei Xiong, Zebin Zhu, Linhe Wang, Lei Lv, Jiyou Yao, Linan Zhang, Longjuan Zhang, Zhiyong Guo
It has been shown that combined liver-kidney normothermic machine perfusion (NMP) is able to better maintain the circuit's biochemical milieu. Nevertheless, whether the combined perfusion is superior to liver perfusion alone in protecting livers from donation after circulatory death (DCD) is unclear. We aimed to test the hypothesis and explored the mechanisms. Livers from 15 DCD pig donors were subjected to either static cold storage (group A), liver-alone NMP (group B), or combined liver-kidney NMP (group C)...
January 2018: Liver Transplantation
Pankaj Jain, Roslyn A Prichard, Mark B Connellan, Kumud K Dhital, Peter S Macdonald
In this 'paired' case report, we describe two heart transplants performed 3 days apart at our centre. Both cases involved very prolonged transportation time of the donor heart. In one case, the donor heart was transported in an ice chest, while in the other case the organ was transported using a normothermic ex vivo perfusion (NEVP) system. The additional retrieval costs incurred by the use NEVP were more than offset by the reduction in subsequent inpatient costs.
October 2017: Internal Medicine Journal
Stephanie F Smith, Thomas Adams, Sarah A Hosgood, Michael L Nicholson
BACKGROUND: Argon has shown potential as an organoprotective agent in numerous models of ischemia-reperfusion injury (IRI). The aim of this study was to evaluate the effects of argon gas during ex vivo normothermic perfusion (EVNP) in an experimental porcine model of kidney IRI. MATERIALS AND METHODS: After a warm ischemia time of 15 min and 17 h of static cold storage, porcine kidneys underwent 1 h of EVNP using leukocyte-depleted blood. During EVNP, kidneys were perfused with a gas composition either of 70% argon (n = 6), 70% nitrogen control (n = 6), or standard 95% oxygen (n = 6) balanced with 5% carbon dioxide...
October 2017: Journal of Surgical Research
Annemarie Weissenbacher, James Hunter
PURPOSE OF REVIEW: Normothermic machine perfusion (NMP) is a preservation method that is generating increasing interest. The aim of this review is to summarise the current status of NMP in regards of kidney viability assessment, reducing organ damage and improving transplant logistics. RECENT FINDINGS: The results of recent large animal experiments and clinical trials show that continuous prolonged normothermic ex-vivo kidney perfusion appears better than a brief period of NMP after static cold storage in terms of renal injury and function...
December 2017: Current Opinion in Organ Transplantation
J Moritz Kaths, Mátyás Hamar, Juan Echeverri, Ivan Linares, Peter Urbanellis, Jun Yu Cen, Sujani Ganesh, Luke S Dingwell, Paul Yip, Rohan John, Darius Bagli, Istvan Mucsi, Anand Ghanekar, David Grant, Lisa A Robinson, Markus Selzner
Normothermic ex vivo kidney perfusion (NEVKP) represents a novel approach for graft preservation and functional improvement in kidney transplantation. We investigated whether NEVKP also allows graft quality assessment before transplantation. Kidneys from 30-kg pigs were recovered in a model of heart-beating donation (group A) after 30 minutes (group B) or 60 minutes (group C) (n = 5/group) of warm ischemia. After 8 hours of NEVKP, contralateral kidneys were resected, grafts were autotransplanted, and the pigs were followed for 3 days...
September 10, 2017: American Journal of Transplantation
Jiajia Cui, Lingfeng Qin, Junwei Zhang, Parwiz Abrahimi, Hong Li, Guangxin Li, Gregory T Tietjen, George Tellides, Jordan S Pober, W Mark Saltzman
Human endothelial cells are initiators and targets of the rejection response. Pre-operative modification of endothelial cells by small interfering RNA transfection could shape the nature of the host response post-transplantation. Ablation of endothelial cell class II major histocompatibility complex molecules by small interfering RNA targeting of class II transactivator can reduce the capacity of human endothelial cells to recruit and activate alloreactive T cells. Here, we report the development of small interfering RNA-releasing poly(amine-co-ester) nanoparticles, distinguished by their high content of a hydrophobic lactone...
August 4, 2017: Nature Communications
Daniel Urcuyo, Matthew F Blum, Qiang Liu, Ahmed Nassar, Laura D Buccini, Teresa Diago Uso, Emilio D Poggio, William M Baldwin Iii, David A Goldfarb, Cristiano Quintini
PURPOSE: Ex vivo perfusion of marginal kidney grafts offers the chance to expand the donor pool, but there is no current clinical standard for the prolonged warm perfusion of renal grafts. This exploratory pilot study seeks to identify a stable ex vivo kidney perfusion model that can support low intravascular resistance and preserve histologic architecture in a porcine donation after cardiac death (DCD) model. METHODS: 15 kidneys were preserved in 1 of 3 settings: normothermic whole blood (NT-WB), normothermic Steen Solution™ (XVIVO Perfusion) with whole blood (NT-Steen/WB), or subnormothermic Steen Solution™ at 21°C (SNT-Steen)...
June 9, 2017: International Journal of Artificial Organs
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