scholarly journals The effect of blood cells retained in rat livers during static cold storage on viability outcomes during normothermic machine perfusion

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Omar Haque ◽  
Casie A. Pendexter ◽  
Benjamin T. Wilks ◽  
Ehab O. A. Hafiz ◽  
James F. Markmann ◽  
...  
Keyword(s):  
Cold Storage ◽  
Blood Cells ◽  
Energy Charge ◽  
Ischemic Injury ◽  
Machine Perfusion ◽  
University Of Wisconsin ◽  
Normothermic Machine Perfusion ◽  
Preservation Solutions ◽  
Positive Correlations ◽  
Rat Livers

AbstractIn transplantation, livers are transported to recipients using static cold storage (SCS), whereby livers are exposed to cold ischemic injury that contribute to post-transplant risk factors. We hypothesized that flushing organs during procurement with cold preservation solutions could influence the number of donor blood cells retained in the allograft thereby exacerbating cold ischemic injury. We present the results of rat livers that underwent 24 h SCS after being flushed with a cold University of Wisconsin (UW) solution versus room temperature (RT) lactated ringers (LR) solution. These results were compared to livers that were not flushed prior to SCS and thoroughly flushed livers without SCS. We used viability and injury metrics collected during normothermic machine perfusion (NMP) and the number of retained peripheral cells (RPCs) measured by histology to compare outcomes. Compared to the cold UW flush group, livers flushed with RT LR had lower resistance, lactate, AST, and ALT at 6 h of NMP. The number of RPCs also had significant positive correlations with resistance, lactate, and potassium levels and a negative correlation with energy charge. In conclusion, livers exposed to cold UW flush prior to SCS appear to perform worse during NMP, compared to RT LR flush.

scholarly journals The effect of blood cells retained in rat livers during static cold storage on viability outcomes during normothermic machine perfusion

2021 ◽  
Author(s):  
Omar Haque ◽  
Casie A. Pendexter ◽  
Benjamin T. Wilks ◽  
Ehab O. A. Hafiz ◽  
James F. Markmann ◽  
...  
Keyword(s):  
Cold Storage ◽  
Blood Cells ◽  
Energy Charge ◽  
Ischemic Injury ◽  
Machine Perfusion ◽  
University Of Wisconsin ◽  
Normothermic Machine Perfusion ◽  
Preservation Solutions ◽  
Positive Correlations ◽  
Rat Livers

Abstract In transplantation, livers are transported to recipients using static cold storage (SCS), whereby livers are exposed to cold ischemic injury that contribute to post-transplant risk factors. We hypothesized that flushing organs during procurement with cold preservation solutions could influence the number of donor blood cells retained in the allograft thereby exacerbating cold ischemic injury. We present the results of rat livers that underwent 24h SCS after being flushed with a cold University of Wisconsin (UW) solution versus room temperature (RT) lactated ringers (LR) solution. These results were compared to livers that were not flushed prior to SCS and thoroughly flushed livers without SCS. We used viability and injury metrics collected during normothermic machine perfusion (NMP) and the number of retained peripheral cells (RPCs) measured by histology to compare outcomes. Compared to the cold UW flush group, livers flushed with RT LR had lower resistance, lactate, AST, and ALT at 6 hours of NMP. The number of RPCs also had significant positive correlations with resistance, lactate, and potassium levels and a negative correlation with energy charge. In conclusion, livers exposed to cold UW flush prior to SCS appear to perform worse during NMP, compared to RT LR flush.

scholarly journals PRESERVAÇÃO DE FÍGADOS HUMANOS COM PERFUSÃO EX-VIVO: UMA VISÃO DO ESTADO DA ARTE

2017 ◽  
Vol 20 (1) ◽  
pp. 20-24
Author(s):  
Samuel Roque Alves ◽  
Lucas Medeiros Lopes ◽  
Ivelise Regina Canito Brasil
Keyword(s):  
Cold Storage ◽  
Ex Vivo ◽  
Ex Situ ◽  
Machine Perfusion ◽  
University Of Wisconsin ◽  
Hypothermic Machine Perfusion ◽  
Normothermic Machine Perfusion

SCS (Static Cold Storage) é a técnica mais utilizada para preservação de órgãos. A HMP (Hypothermic Machine Perfusion) foi inicialmente proposta por Belzer, nos anos 1960. A NMP (Normothermic machine perfusion) evita isquemia fria, mantém a função hepática, monitora a função do enxerto em tempo real pelo fluxo de produção de bile. O presente trabalho visa sumarizar estudos de preservação hepática ex-situ e os resultados com diferentes combinações de parâmetros, dando enfoque aos trabalhos com fígados humanos. Realizamos revisão da literatura, selecionamos 73 artigos, sendo 15 revisões de literatura e 58 estudos experimentais. Destes, oito foram realizados em humanos, 12 em porcos e 39 em ratos. Dos oito estudos com fígados humanos, cinco utilizaram HMP, dois utilizaram SNMP e um utilizou NMP. Todos mostraram melhora da função do enxerto e marcadores bioquímicos de lesão. Quanto às soluções utilizadas, a maioria usou a solução UW (University of Wisconsin), enquanto um trabalho utilizou solução de concentrado de hemácias. O tempo de perfusão variou de 30 minutos a 24 horas. A utilização de órgãos critério-expandidos surge como alternativa para pacientes esperando transplante. As máquinas de perfusão estão cada vez mais presentes no contexto do transplante de órgãos sólidos e serão essenciais para redução das filas de espera, fornecendo maior número de enxertos viáveis para transplante. O desenvolvimento de máquinas viáveis e práticas para perfusão de fígados humanos já está se tornando realidade e representa o futuro do transplante de fígado; espera-se que mais modelos e protocolos sejam testados nos próximos anos e passem a ter utilização clínica rotineira.

scholarly journals Physiological effects of altering oxygenation during kidney normothermic machine perfusion

2019 ◽  
Vol 316 (5) ◽  
pp. F823-F829 ◽  
Author(s):  
Thomas D. Adams ◽  
Sarah A. Hosgood ◽  
Michael L. Nicholson
Keyword(s):  
Blood Flow ◽  
Renal Function ◽  
Renal Blood Flow ◽  
Cold Storage ◽  
Ischemic Injury ◽  
Warm Ischemia ◽  
Oxygen Extraction ◽  
Machine Perfusion ◽  
Oxygen Extraction Ratio ◽  
Normothermic Machine Perfusion

Kidney normothermic machine perfusion (NMP) has historically used a 95% O2-5% CO2 gas mixture. Using a porcine model of organ retrieval, NMP, and reperfusion, we tested the hypothesis that reducing perfusate oxygenation ([Formula: see text]) would be detrimental to renal function and cause injury. In the minimal ischemic injury experiment, kidneys sustained 10 min of warm ischemia and 2 h of static cold storage before 1 h of NMP with either 95%, 25%, or 12% O2 with 5% CO2 and N2 balance. In the clinical injury experiment, kidneys with 10-min warm ischemia and 17-h static cold storage underwent 1-h NMP with the above gas combinations or 18-h static cold storage as a control. They were then reperfused with whole blood and 95% O2 for 3 h. Overall, reducing [Formula: see text] did not significantly influence renal function in either experiment. Furthermore, there were no differences in the injury markers urinary neutrophil gelatinase-associated lipocalin or tissue high-motility group box protein 1. In the minimal ischemic injury experiment, a [Formula: see text] of 25% significantly reduced renal blood flow and increased vascular resistance. Oxygen delivery, consumption, and extraction (oxygen extraction ratio) were significantly greater at 95% [Formula: see text]. In the clinical injury experiment, renal blood flow was significantly increased at 25% [Formula: see text] and Na+ excretion decreased. At 95% [Formula: see text], the oxygen content and oxygen extraction ratio were significantly increased. During reperfusion, renal blood flow was significantly increased in the 25% group. The control group pH was significantly decreased compared with the 25% group. Our data suggest that reducing [Formula: see text] during NMP does not have detrimental effects on renal function or markers of injury.

scholarly journals Human liver stem cell‐derived extracellular vesicles reduce injury in a model of normothermic machine perfusion of rat livers previously exposed to a prolonged warm ischemia

2021 ◽  
Vol 34 (9) ◽  
pp. 1607-1617
Author(s):  
Nicola De Stefano ◽  
Victor Navarro‐Tableros ◽  
Dorotea Roggio ◽  
Alberto Calleri ◽  
Federica Rigo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Extracellular Vesicles ◽  
Human Liver ◽  
Warm Ischemia ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion ◽  
Rat Livers

scholarly journals Impact of Red Blood Cells on Function and Metabolism of Porcine Deceased Donor Kidneys During Normothermic Machine Perfusion

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Leonie H. Venema ◽  
L. Leonie van Leeuwen ◽  
Rene A. Posma ◽  
Harry van Goor ◽  
Rutger J. Ploeg ◽  
...  
Keyword(s):  
Red Blood Cells ◽  
Blood Cells ◽  
Deceased Donor ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion

Visualization of Endothelial Cell Structure During Machine Perfusion Preservation of Livers

2002 ◽  
Author(s):  
Shailendra Jain ◽  
Saurin Purohit ◽  
Jian Zhang ◽  
Mark G. Clemens ◽  
Charles Y. Lee
Keyword(s):  
Confocal Microscopy ◽  
Red Blood Cells ◽  
Blood Cells ◽  
Cell Structure ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Machine Perfusion ◽  
Success Rates ◽  
University Of Wisconsin ◽  
Heart Beating

The development of machine perfusion preservation (MPP) of kidney has led to significant improvements and greater success rates in kidney transplantation by providing superior preserved tissue and viable non-heart-beating donor tissue. However, machine perfusion of livers has not been successful in improving preservation. Currently, the major cause of damage associated with MPP of livers remains unclear. Previous studies showed increased vascular resistance and blockages during and after 24hrs MPP but no direct evidence existed. Utilizing a novel two colors fluorophores labeling, an intravital microscopic study was conducted to obtain real time images and confocal microscopy to get detailed images in order to correlate fluorescent-tagged endothelial cells (ECs) with red cell stasis. Fluorescein isothiocynate (FITC) was used to label red blood cells (RBCs) and DiI acetylated low-density lipoprotein (DiI acLDL) was used to mark ECs. Structure of ECs was recorded and assessed during 24hrs MPP with University of Wisconsin (UW) solution at 4°C with a flow rate of 4ml/min. Images recorded from intravital microscopy and confocal microscopy show ECs rounding over a period of 24 hrs and subsequent red blood cells stasis after 24hrs MPP and during rewarming.

scholarly journals Normothermic Machine Perfusion versus Cold Storage of Liver in Pig Model: A Meta-Analysis

2018 ◽  
Vol 23 ◽  
pp. 197-206 ◽  
Author(s):  
Shiqi Bian ◽  
Zhijun Zhu ◽  
Liying Sun ◽  
Lin Wei ◽  
Wei Qu ◽  
...  
Keyword(s):  
Cold Storage ◽  
Meta Analysis ◽  
Pig Model ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion

scholarly journals Twenty-four hour ex-vivo normothermic machine perfusion in rat livers

TECHNOLOGY ◽  
2020 ◽  
pp. 1-10
Author(s):  
Omar Haque ◽  
Casie A. Pendexter ◽  
Stephanie E.J. Cronin ◽  
Siavash Raigani ◽  
Reiner J. de Vries ◽  
...  
Keyword(s):  
Rat Liver ◽  
Ex Vivo ◽  
Liver Perfusion ◽  
Therapeutic Interventions ◽  
Liver Graft ◽  
Large Animal ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion ◽  
Organ Quality ◽  
Rat Livers

Ex-vivo liver perfusion (EVLP) is an ideal platform to study liver disease, therapeutic interventions, and pharmacokinetic properties of drugs without any patient risk. Rat livers are an ideal model for EVLP due to less organ quality variability, ease of hepatectomy, well-defined molecular pathways, and relatively low costs compared to large animal or human perfusions. However, the major limitation with rat liver normothermic machine perfusion (NMP) is maintaining physiologic liver function on an ex-vivo machine perfusion system. To address this need, our research demonstrates 24-hour EVLP in rats under normothermic conditions. Early (6 hour) perfusate transaminase levels and oxygen consumption of the liver graft are shown to be good markers of perfusion success and correlate with viable 24-hour post-perfusion histology. Finally, we address overcoming challenges in long-term rat liver perfusions such as rising intrahepatic pressures and contamination, and offer future directions necessary to build upon our work.

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