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Hypoxia, Free Radicals, and Reperfusion Injury Following Cold Storage and Reperfusion of Livers for Transplantation
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Ronald G. Thurman, Wenshi Gao, Henry D. Connor, Sigrid Bachmann, Robert T. Currin, Ronald P. Mason, John J. Lemasters
Kupffer cells make up 80 to 90% of all tissue macrophages in the body.148 When activated, Kupffer cells release oxygen radicals, nitric oxide, eicosanoids, proteases, TNF, and other cytokines.149 These compounds likely intensify inflammatory responses and microcirculatory disturbances already caused by injury to the vascular endothelium (Figure 4). Spin trapping techniques and nitroblue tetrazolium cytochemistry have demonstrated oxygen radical formation by stored and reperfused liver grafts directly.133,150 These radicals may lead to neutrophil margination and further inflammatory injury, since superoxide dismutase decreases neutrophil infiltration into reperfused liver following both warm and cold ischemia.151,152 The adult respiratory distress syndrome and multiple organ failure associated with primary graft failure may be due to systemic release of soluble toxic mediators by activated Kupffer cells and possibly other cell types.112,114,153
Nonsuture Cuff Technique for Organ Transplantation in the Rat
Published in Waldemar L. Olszewski, CRC Handbook of Microsurgery, 2019
M. Olausson, L. Mjörnstedt, Hans Brynger
When the donor and recipient operations are performed simultaneously, the warm ischemia time is short (1 to 2 min), which is the time needed for connecting the donor vessels to the recipient vessels. This should be compared with the conventional suture technique where the warm ischemia time usually is between 15 to 25 min. The cold ischemia time corresponds to the operation time.
Pancreas transplantation
Published in Demetrius Pertsemlidis, William B. Inabnet III, Michel Gagner, Endocrine Surgery, 2017
As perioperative complication rate and long-term graft survival correlate to a great extent with quality of the donor, most transplant centers use strict acceptance inclusion criteria. Although a few centers use partial pancreas grafts from living donors, the vast majority are from deceased donors, and mostly from donors after brain death (DBDs) [3]. The major factors that determine donor organ quality are age (common cutoff 30–40), BMI (common cutoff 25–30), and kidney function, which is a marker of end-organ perfusion [15–18]. Intraoperative assessment of the surgeon is important, and not infrequently, organs are found to have excessive fat deposition or fibrosis and are discarded at the time of retrieval. Steatotic organs have an increased risk of posttransplant pancreatitis secondary to reperfusion injury [16]. A donor history of significant alcohol use is also a common exclusion criterion. Recently, a systematic evaluation of pancreas allograft quality using the Scientific Registry of Transplant Recipients (SRTR) data was done to construct a pancreas donor risk index (PDRI) [18], aimed to predict long-term graft function. The PDRI included 10 donor and 1 transplant characteristics. Donor factors include donor sex, cause of death, creatinine, height, and donation after cardiac death (DCD). The transplant-related factor was preservation time, or cold ischemia time. Donor age, BMI, and DCD status were found to have the greatest impact on risk for graft loss during the first year posttransplant.
Devices for donor lung preservation
Published in Expert Review of Medical Devices, 2022
Cora R Bisbee, Curry Sherard, Jennie H. Kwon, Zubair A. Hashmi, Barry C. Gibney, Taufiek Konrad Rajab
Central to the idea of donor organ preservation is the concept of balancing metabolic demand and hypoxic injury during transport and storage. Cold preservation reduces oxygen demand and aerobic metabolism as enzymes in the citric acid cycle and pyruvate oxidation are inhibited [4]. However, these reduced temperatures can denature proteins leading to cell destabilization and reactive oxygen species, ultimately causing cell necrosis and apoptosis [5]. Donor organs stored in higher temperatures raise metabolic demand for oxygen leading to hypoxic injury and impaired organ function [4]. Ideally, a balanced temperature minimizing the effects of these two extremes can be found. To reduce the harmful effects of cold ischemic storage, organs are flushed with preservation solutions that assist in decelerating metabolism while simultaneously providing an environment that maintains tissue viability [5]. The biology behind cold ischemia, warm ischemia, and preservation solutions are at the cornerstone of lung transplant preservation strategies.
Current Status of Liver Transplantation Using Marginal Grafts
Published in Journal of Investigative Surgery, 2020
Amr Badawy, Toshimi Kaido, Shinji Uemoto
Prolonged cold ischemia time usually exacerbates the hepatic ischemia/reperfusion injury leading to increased risk of primary nonfunction, delayed graft function, ischemic cholangiopathy and graft loss [60,79]. In 2018, Pan et al. [80] conducted a retrospective analysis using the United Network for Organ Sharing (UNOS) database. They analyzed the data of 67,426 recipients and observed that CIT between 9 and 16 h was associated with increased risk of graft loss. However, a study by Grat et al. [81] found that prolonged CIT (≥9 h) had no effect on 5-year graft survival in low MELD recipients (<10), while it was an independent risk factor for poor 5-year graft survival in high MELD recipients (>20). Also, they noticed that older donor age (>46 years) provoked the negative effect of prolonged CIT on graft survival in recipients with MELD score between 10 and 20. Therefore, it was suggested by several studies that prolonged CIT if associated with other donor or recipient risk factors such as older donors, graft steatosis, recipient high MELD score, obesity, and diabetes mellitus would significantly increase the risk of graft loss [79,81–83].
L-Carnitine and Potential Protective Effects Against Ischemia-Reperfusion Injury in Noncardiac Organs: From Experimental Data to Potential Clinical Applications
Published in Journal of Dietary Supplements, 2018
Azadeh Moghaddas, Simin Dashti-Khavidaki
Preserving organs in cold storage fluid is always a matter of interest. The potential protective effects of LC have been established in cold preservation fluid as described in the hepatic injury section. This issue has been assessed in a comprehensive study conducted in 2005. The study was performed in an isolated perfused kidney, which already had injury. The aim of this study was to explore whether addition of PLC during cold storage of the donor kidney prevents I/R injury and facilitates immediate graft function. Data revealed that pre-ischemia exposure of kidneys to PLC largely prevented renal function impairment in the isolated perfused kidney. Histologic findings in the PLC-administrated group showed very mild post-ischemic kidney lesions compared with untreated ischemic kidneys. Adding PLC to organ preservation solution during cold ischemia largely preserved the organ as compared to untreated ischemic grafts. Furthermore, addition of PLC to Belzer UW solution prevented PMN cell graft infiltration and reduced tubular injury in the first hours after transplantation, which may be attributed to I/R protection. These new achievements will probably be important in posttransplant delayed graft function treatment modalities (Mister et al., 2002).