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Purpose: To develop and validate a perfused organ model for characterizing ablations for irreversible electroporation (IRE)-based therapies.
Materials And Methods: Eight excised porcine livers were mechanically perfused with a modified phosphate-buffered saline solution to maintain viability during IRE ablation. IRE pulses were delivered using 2 monopolar electrodes over a range of parameters, including voltage (1,875-3,000 V), pulse length (70-100 µsec), number of pulses (50-600), electrode exposure (1.0-2.0 cm), and electrode spacing (1.5-2.0 cm). Organs were dissected, and treatment zones were stained with triphenyl tetrazolium chloride to demonstrate viability and highlight the area of ablation. Results were compared with 17 in vivo ablations performed in canine livers and 35 previously published ablations performed in porcine livers.
Results: Ablation dimensions in the perfused model correlated well with corresponding in vivo ablations (R = 0.9098) with a 95% confidence interval of < 2.2 mm. Additionally, the validated perfused model showed that the IRE ablation zone grew logarithmically with increasing pulse numbers, showing small difference in ablation size over 200-600 pulses (3.2 mm ± 3.8 width and 5.2 mm ± 3.9 height).
Conclusions: The perfused organ model provides an alternative to animal trials for investigation of IRE treatments. It may have an important role in the future development of new devices, algorithms, and techniques for this therapy.
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http://dx.doi.org/10.1016/j.jvir.2016.07.012 | DOI Listing |
PLoS One
September 2025
Department of Cardiac Surgery, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Background: Cardiac ischemia reperfusion (I/R) injury is a serious consequence of reperfusion therapy for myocardial infarction (MI). Peptidylarginine deiminase 4 (PAD4) is a calcium-dependent enzyme that catalyzes the citrullination of proteins. In previous studies, PAD4 inhibition protected distinct organs from I/R injury by preventing the formation of neutrophil extracellular traps (NETs) and attenuating inflammatory responses.
View Article and Find Full Text PDFFront Cardiovasc Med
August 2025
Department of Surgery, Heart Institute, Morsani College of Medicine, University of South Florida, Tampa, FL, United States.
Protein kinases have crucial roles in intracellular signal transduction pathways that affect a wide range of biochemical processes, including apoptosis, metabolism, proliferation, and protein synthesis. Vascular endothelial cells are important regulators of vasomotor tone, tissue/organ perfusion, and inflammation. Since its discovery in the late 1970s, a growing body of literature implicates protein kinase C (PKC) in pathways involving angiogenesis, endothelial permeability, microvascular tone, and endothelial activation.
View Article and Find Full Text PDFExp Clin Transplant
August 2025
>From the Division of Transplant Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; and the Sackler School of Medicine at Tel Aviv University, Tel Aviv, Israel.
Objectives: On-site normothermic machine perfusion of the liver may require hepatic arterial reconstruction. The effect of arterial reconstruction on the deve-lopment of primary ischemic cholangiopathy has not been fully elucidated in liver transplants with organs donated after circulatory death. The aim of this study was to evaluate the effect of normothermic machine perfusion with arterial reconstruction at the onset of ischemic cholangiopathy in liver transplants with organs donated after circulatory death.
View Article and Find Full Text PDFNat Rev Nephrol
September 2025
Nuffield Department of Surgical Sciences, University of Oxford, Oxford, UK.
The global shortage of suitable donor kidneys is the primary challenge in kidney transplantation, and it is exacerbated by ageing donors with increased numbers of health issues. Improving organ assessment, preservation and conditioning could enhance organ utilization and patient outcomes. Hypothermic machine perfusion (HMP) is associated with better results than static cold storage by reducing delayed graft function and improving short-term graft survival, especially in kidneys recovered from marginal-quality donors.
View Article and Find Full Text PDFPerfusion
September 2025
Department of Surgery, Columbia University, New York, NY, USA.
Static cold storage (SCS) on ice has remained the gold standard preservation method for heart transplantation, and prolonged cold ischemia outside the typical 4-6 hour window is associated with an increased risk of primary graft dysfunction - a consequence attributed to ischemic damage and reperfusion injury. This, unfortunately limits the travel radius for donor heart procurement, a key factor that contributes to the overall shortage of donor organs. Recent research and clinical data have illustrated the validity of other preservation systems in preserving cardiac allografts, and many of these devices have shown promise in potentially prolonging the tolerated ischemic time beyond the accepted standard.
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