Warm Ischemic Damage Research Articles

Abstract 4147630: Towards transplantation of hearts from donation after circulatory death - stem cell derived therapy for ameliorating donor organ damage

The use of heart transplantation (HTx), a key life-saving therapy for end-stage heart failure, is limited by the shortage of acceptable donor hearts. Although donation after circulatory death (DCD) offers a potentially promising resource for clinical transplantation, its adoption for HTx is concerned by warm ischemic damage during the death process. Mesenchymal stem cell (MSC)-derived paracrine action has been proved to mediate cardioprotection. Based on our previous study showing that MSC conditioned media (MSC CM) and MSC-exosomes (MSC Exo) confer improved donor heart preservation during cold ischemic storage, we aimed to test the effect of MSC CM and MSC Exo on ex vivo recovery of ischemia-damaged myocardium and on promoting the implanted DCD heart function using an in vivo murine heterotopic heart transplantation model. Methods: Donor hearts from adult male C57BL/6 mice with 0, 30’ or 50’ in vivo warm ischemia (WI) were divided into (n=5-7/group): 1) no WI; 2) 30’-WI; 3) 50’-WI; 4) no WI+4h cold storage at 0-4°C (no WI+CS); 5) 30’-WI+CS; 6) 50’-WI+CS; 7) 50’-WI+CS+vehicle; 8) 50’-WI+CS+MSC CM; and 9) 50’-WI+CS+MSC Exo. The CM and Exo were obtained from cultivation of human bone marrow-MSCs in serum-free media for 72h and was added into preservation solution. Donor hearts were implanted into C57BL/6 male recipients using cervical heterotopic heart transplantation. At 24h post-surgery, left ventricular (LV) function was detected in transplanted hearts. Abdominal artery pressure was measured in recipients to validate technical reproducibility of the HTx model. Mitochondrial structure was detected by electron microscopy on the fixed human LV (hDCD&hDBD). Results: WI significantly impaired LV function in transplanted DCD hearts vs. no-WI (Fig. A, B). Intriguingly, markedly improved graft function was observed in MSC CM- or Exo-treated DCD hearts vs. vehicle (Fig. C). Short and disrupted cristae in mitochondria were noticed in hDCD vs. hDBD (Fig. D). Conclusions: Our results represent the initial evidence that MSC secretome (CM&Exo) mediates ex vivo cardiac repair in DCD hearts and validate an approach on MSC derived therapy to rescue marginal DCD donor hearts and improve post-transplant graft function.

O169: The impact of time to death in donors after circulatory death on recipient outcome in simultaneous pancreas-kidney transplantation

Abstract Background Agonal times can vary between organ donors after circulatory death (DCD) following withdrawal of treatment, which leads to variable warm ischaemic damage to pancreas grafts. Currently there is little evidence supporting procurement team standdown times based on donor time to death (TTD). We examined what impact TTD had on pancreas graft outcomes following DCD transplantation. Methods Data were extracted from the UK transplant registry from 2014 to 2022. TTD was defined as withdrawal of life-sustaining treatment to donor asystole; asystolic time was the time from asystole to aortic perfusion. Predictors of graft loss were fitted into a Cox proportional hazards model. Adjusted restricted cubic spline (RCS) models were generated to further delineate the relationship between TTD and outcome. Statistical significance was set at P<0.05. Results 375 DCD simultaneous kidney-pancreas transplant recipients were included. Median TTD was 13-minutes (IQR 10 to 16-minutes), median asystolic time was 13-minutes (IQR 11 to 15-minutes). Increasing TTD was not associated with poorer graft survival (aHR 0.98, 95% CI 0.68-1.41, P=0.901). Increasing asystolic time was significantly associated with worse graft survival in the TTD model (aHR 2.51, 95%CI 1.16-5.43, P=0.020). RCS modelling confirmed there was no relationship between TTD and graft survival, however a non-linear relationship was demonstrated between asystolic time and graft survival. Conclusion We found no evidence that TTD impacts pancreas graft survival in DCD SPK transplantation, however increasing asystolic time was significant predictors of graft loss. Procurement teams should attempt to minimise asystolic time to reduce ischaemic injury to the pancreas graft.

Understanding the Brain-based Determination of Death When Organ Recovery Is Performed With DCDD In Situ Normothermic Regional Perfusion.

Understanding the Brain-based Determination of Death When Organ Recovery Is Performed With DCDD In Situ Normothermic Regional Perfusion.

Evaluation of the safety of retroperitoneal laparoscopic partial nephrectomy by investigating the perioperative indicators.

In recent years, open nephron sparing partial nephrectomy (OPN) has been gradually applied and generally accepted. Recent statistical data show that PN not only can safely and effectively preserve the functional nephron, but also has fewer complications, low local recurrence rate and no significant difference in long-term survival rate compared with nephrectomy/radical nephrectomy, which has gradually become a routine treatment for small renal cell carcinoma. Therefore, how to maximize the protection of postoperative residual renal function (RRF) and reduce the risk of CKD while achieving the ideal local and overall tumor control effect is the key to the treatment of renal cancer, and is also the focus of attention of urologists and nephrologists. To evaluate the safety of retroperitoneal laparoscopic partial nephrectomy (RLPN) by investigating the perioperative indicators and postoperative follow-up. A total of 40 hospitalized patients in our hospital from December 2019 to December 2021 were selected and followed up for a long time. Patients with renal tumors less than 4cm in diameter and exogeneous or partial exogeneity were randomly divided into 2 groups. Patients in retroperitoneal laparoscopic group (n = 20) were treated with nephron sparing partial nephrectomy (0.5-1cm). Twenty patients underwent retroperitoneal laparoscopic radical nephrectomy (LRN).The time of removal of drainage tube, drainage volume, time of feeding activity and postoperative hospital stay were recorded, and the safety of the operation was evaluated. nephron sparing partial nephrectomy is suitable for patients with localized renal carcinoma or benign tumor <4cm. RLPN can be applied to all indications of open nephron sparing partial nephrectomy (OPN), with good safety, and can preserve residual renal function to the greatest extent. The operative vascular occlusion time was controlled within 40 minutes, and the use of renal function protection measures during the operation was safe and controllable in reducing the prevention of warm ischemic kidney damage, with good safety. The renal tumor capsule with 0.5cm~1cm margin was complete by postoperative pathology. In the process of tumor resection and suture collection system in the RLPN group, we improved the previous operation of "resection before hemostasis" to "resection while hemostasis" and "knot-free suture" technology, which saved the operation time of intracavity suture knotting. Reduced cortical tear caused by vertical pull during knot tying. The combined effect of biological clip and hemostatic gauze can stimulate the granulation proliferation of renal cortical wound and accelerate the repair. With the combination of knot-free suture and renal segment vascular occlusion, hot ischemic kidney damage is reduced. In the RLPN group, there were no complications of urinary fistula and bleeding, and no abnormal changes in renal function during follow-up. The safety of RLPN group is worthy of affirmation. The perioperative safety and short-term postoperative renal function recovery of RLPN are good, and the overall safety of this operation is worthy of affirmation.

Direct Lung Procurement with Ongoing Abdominal Normothermic Regional Perfusion

<h3>Introduction</h3> Donation after circulatory death (DCD) has recently advanced with abdominal normothermic regional perfusion (A-NRP). The A-NRP technique has been implemented to minimize warm ischemic damage to the abdominal organs significantly improving recipient outcomes. There is now a necessity for a standardized and reproducible technique for direct procurement of cardiothoracic organs while A-NRP is ongoing. <h3>Case Report</h3> There were seven successful lung retrievals in the presence of A-NRP that we have performed and reporting. The mean age of the donors was 40 with 4 males. A-NRP was established either via femoral vessels or via the abdominal vessels after laparotomy while the chest was opened simultaneously. The cardiothoracic organs were isolated by application of vascular clamps to decending aorta, SVC caudal to azygos vein and the supradiaphragmatic IVC. Following antegrade pneumoplegia, cardiectomy was performed. After delivering retrograde pneumoplegia, lungs were carefully retrieved with meticulous hemostasis by using liga clips, stitches and diathermy allowing 2 hours of uninterrupted A-NRP in each of the seven successful lung procurements. In all the cases, there was a successful completion of A-NRP without blood loss in the chest. No thoracic cell salvage was required. All lungs once procured, were placed in cold saline, transported on ice to the implanting or research center. Two double and one single left lung (severe right-side consolidation) were successfully transplanted with good short-mid term outcome along with procurement and transplantation of abdominal organs. One pair of lungs was placed on EVLP but declined due to insufficient improvement. Three lungs were procured purely for research <h3>Summary</h3> Direct Lung procurement with A-NRP is a challenging retrieval technique requiring optimal coordination of the abdominal and thoracic retrieval teams. We have successfully performed seven retrievals with 100% successful completion of A-NRP consistently which is first in the world.

The airflow and cooling characteristics in the airway of NHBD lung with hypothermic ventilation

Hypothermic ventilation through trachea can cool Non-heart beating donor (NHBD) lungs noninvasively in vivo, thus avoiding warm ischemic damage. However, previous experimental studies with large lungs have shown poor cooling effect in bronchial terminal of NHBD lungs. To investigate the airflow and cooling characteristics of this process, a physiologically realistic upper airway model was established. In addition, droplet spraying was considered to enhance the heat transfer during the cooling process. The results show that the irregular geometry of realistic airway will lead to non-uniformity distribution of internal flow and temperature, and the local cooling effect in different regions is related to the velocity distribution. The secondary flow at the bifurcation can forcibly strengthen the heat exchange between the cold air and the hot air in the nearby low-speed area. Increasing the ventilation flow will strengthen the turbulence and heat exchange in the airway, so as to improve the overall cooling effect. The synergistic effect of cold air and droplet spraying can enhance the cooling effect in the airway. And large droplets (i.e. 10 μm) are conducive to the cooling enhancement of the central airway, while small droplets (i.e. 2 μm) are conducive to the cooling of the distal bronchus.

Current review of machine perfusion in liver transplantation from the Japanese perspective.

In light of the present evidence, machine perfusion is opening up new horizons in the field of liver transplantation. Although many advances have been made in liver transplantation, organ preservation methods have so far changed very little. Static cold storage is universally used for graft preservation in liver transplantation; however, there is a need for better preservation methods, such as ex vivo machine perfusion, to improve the outcomes by decreasing warm ischemic damage. Based on the findings of basic and clinical trials, hypothermic and normothermic machine perfusion techniques are now commercially available and include the OrganOx metra, Liver Assist, Cleveland NMP device, Organ Care System, and LifePort Liver. Recent clinical trials have provided further evidence for the potential role of normothermic machine perfusion to resuscitate and subsequently improve utilization of marginal or currently discarded livers. Further studies are required to explore the longer-term outcomes, late biliary complications, outcomes in specific high-risk groups, viability biomarkers, optimum and maximum perfusion duration, perfusate composition, and liver-directed therapeutic interventions during normothermic machine perfusion. The use of organs from marginal donors after brain death, such as fatty livers and the livers from elderly donors with multiple comorbidities, may be accepted for machine perfusion in Japan in the near future.

The Use of the Oxygenated AirdriveTM Machine Perfusion System in Kidney Graft Preservation: A Clinical Pilot Study

Background: The shortage of donor kidneys has led to the use of marginal donors, e.g., those whose kidneys are donated after circulatory death. Preservation of the graft by hypothermic machine perfusion (HMP) provides a viable solution to reduce warm ischemic damage. This pilot study was undertaken to assess the feasibility and patient safety of the Airdrive^TM HMP system in clinical kidney transplantation. Methods: Five deceased-donor kidneys were preserved using the oxygenated Airdrive HMP system between arrival at the recipient center (Amsterdam UMC) and implantation in the patient. The main study end-points were adverse effects due to the use of Airdrive HMP. Secondary end-points were clinical outcomes and perfusion parameters. All events occurring during the transplantation procedure or within 1 month of follow-up were monitored. Results: Five patients were included in this pilot study. No technical failures were observed during the preservation period using the Airdrive HMP. Mean perfusion parameters were: duration 8.5 h (3–15 h), pressure 25 mm Hg (18–25 mm Hg), flow 49.77 mL/min (19–58 mL/min), resistance 0.57 mm Hg/min/mL (0.34–1.3 mm Hg/min/mL), and temperature 8.2 °C (2–13°C). Mean cold ischemia time (CIT) was 20.2 h (11–29.5 h). No adverse events or technical failures were observed during preservation and transplantation or during the 1-month follow-up. Conclusions: This pilot study showed the feasibility of the use of the Airdrive HMP system with no adverse events in clinical kidney transplantation.

Effect on the donor lungs of using abdominal normothermic regional perfusion in controlled donation after circulatory death.

Controlled donation after circulatory death (cDCD) donors are becoming a common source of organs for transplantation globally. However, the graft survival rate of cDCD abdominal organs is inferior to that of organs from brain-dead donors. The rapid retrieval (RR) technique is used by most donor organ procurement teams. The abdominal normothermic regional perfusion (A-NRP) technique has been implemented to minimize warm ischaemic damage to the abdominal organs. However, there is limited information on the effect of A-NRP on the quality of the donor lungs. This study aimed to compare lung transplantation outcomes using lungs procured from cDCD donors using the A-NRP and abdominal RR techniques. A single-centre retrospective analysis of consecutive transplant recipients of cDCD lungs from June 2013 to December 2019 was performed. The recipients were divided into 2 cohorts according to the abdominal procurement technique used. The recipient and donor characteristics (age, sex, cause of brain injury, warm ischaemic time, diagnosis, lung allocation score and other factors), incidence of primary graft dysfunction and early survival were monitored. Twenty-eight consecutive lung transplantation recipients were identified (median age 59 years; 61% male); 14 recipients received lungs using the A-NRP and 14 using abdominal RR for abdominal organ retrieval. There were no significant differences in the baseline characteristics, primary graft dysfunction (P = 0.70), hospital mortality (P = 1.0) and 1-year survival rate (P = 1.0) between the 2 groups. No difference was observed in lung transplantation outcomes irrespective of the abdominal organ procurement technique used (A-NRP or abdominal RR).

Determination of Optimal Coronary Flow for the Preservation of "Donation after Circulatory Death" in Murine Heart Model.

Donation after circulatory death donors (DCD) have the potential to increase the number of heart transplants. The DCD hearts undergo an extended period of warm ischemia, which mandates the use of machine perfusion preservation if they are to be successfully recovered for transplantation. Because the minimum coronary artery flow needed to meet the basal oxygen demand (DCRIT) of a DCD heart during machine perfusion preservation is critical and yet unknown, we studied this in a DCD rat heart model. Adult male rats were anesthetized, intubated, heparinized, and paralyzed with vecuronium. The DCD hearts (n = 9) were recovered 30 minutes after circulatory death whereas non-DCD control hearts (n = 12) were recovered without circulatory death. Hearts were perfused through the aorta with an oxygenated Belzer Modified Machine Perfusion Solution (A3-Bridge to Life Ltd. Columbia, SC) at 15°C or 22°C starting at a flow index of 300 ml/100 g/min and decreasing by 40 ml/100 g/min every 10 minutes. Inflow (aortic) and outflow (inferior vena cava) perfusate samples were collected serially to assess the myocardial oxygen consumption index (MVO2) and O2 extraction ratio. The DCRIT is the minimum coronary flow below which the MVO2 becomes flow dependent. The MVO2, DCRIT, and oxygen extraction ratios were higher in DCD hearts compared with control hearts. The DCRIT for DCD hearts was achieved only at 15°C and was significantly higher (131.6 ± 7 ml/100 g/min) compared with control hearts (107.7 ± 8.4 ml/100 gm/min). The DCD hearts sustain warm ischemic damage and manifest higher metabolic needs during machine perfusion. Establishing adequate coronary perfusion is critical to preserving organ function for potential heart transplantation.

(472) - The Interleukin 4 Receptor-α Potentiates the Effect of Oncostatin M Receptor on the Release of FGF23 by Cardiomyocytes

are combined, there are concerns regarding delays to institution of liver cold preservation. The aim of this study was to develop a combined DCD heart and liver retrieval protocol in a pig model with subsequent normothermic machine perfusion (NMP) of both organs to mitigate warm ischemic damage. Methods: Pigs (n= 12; 60-70 kg) were anesthetised. Baseline observations were recorded. After sternotomy, and laparotomy, ventilatory support was withdrawn to mimic DCD conditions. Death was defined as equalisation of central venous and mean arterial pressures. After a 5-minute standoff period, 1.5-2 L blood was collected from a right atrial cannula then a cardiac preservation flush (4°C) commenced via the proximal ascending aorta. The inferior vena cava was cut to vent the organs. The thoracic cavity was kept cold with saline ice slush. The heart was explanted and prepared on back-table for NMP. Liver preservation was begun immediately after blood collection by cold preservation solution flush via the infra-renal aorta and portal vein. The hepatic artery, portal vein and common bile duct were transected, and the liver explanted for back-table NMP preparation. Results: Warm ischaemic time (WIT) and back-table time (BTT) was 21 + 5 and 29 + 6 min for the heart; 20 + 6 (commencement of flush) and 33 + 19 min for the liver. The average blood volume collected was 1.6 L: 1:1 dilution with Krebs resulted in significant hemodilution (from 23 + 5% to 15 + 6%) and hypocalcemia (1.30 + 0.15 to 0.64 + 0.32 mM). This resulted in sub-optimal cardiac contractile recovery despite a favourable lactate profile. Liver enzyme release, bile production, and lactate and pH profiles were favourable during the first 4-6 hours of NMP but deteriorated thereafter. Conclusion: Heart and liver retrieval under standard DCD protocol is possible without excessively extending the WIT for either organ. However, there is insufficient donor blood to support NMP of both organs.

Assessment of eGFR and One-Hour Biopsy Using In-Situ-Cooling Double-Balloon Catheters in Deceased Kidney Transplants.

Introduction and Objectives:The shortage of deceased donor kidneys for transplantation has become a worldwide issue in the past decades. However, both availability and feasibility of marginal deceased donor kidneys are still problematic. To increase donor pool, we created a specially designed in-situ cooling system. The purpose of this study was to estimate availability of deceased donor kidneys, analyze donor one-hour biopsy, and better evaluate methods to estimate donor/recipient kidney function other than using donor Cr, comparing with living related transplants. Materials and Methods:We studied 129 deceased renal transplant recipients (DD) who received kidneys from non-heart-beating donors beginning in 1984. Donors were in Maastricht Donor Categories III and IV and to minimize warm ischemic kidney damage we performed in situ cooling with specially designed double-balloon catheters. Twenty-nine living-related transplants (LD) were a control group. Results:In the DD group average donor Cr and eGFR levels at admission were 0.3-2.1mg/dl (ave. 1.0) and 24-138 ml/min/1.73 (ave. 67) and levels before death were 0.3-15.9 (2.7) and 4-164 (34). Average recipient Cr and eGFR levels at discharge were 0.3-5.3 (1.8) and .10-133 (39). To define kidney function after transplant, the DD were classified according to recipient eGFR at discharge: <25 for the poor function group (PF: n=32) and >25 for the good function group (GF: n=95). GF had higher eGFR levels at donor hospital admission than the PF (p=0.005). There was no statistically significant difference in Cr levels of donor (at admission and before death) between those groups. Pathologically, the DD with less glomerular sclerosis of 1-hour biopsies had better graft survival than damaged subjects (p=0.015). Other histological scores were not associated with kidney survival. Conclusion:Deceased kidney transplants had excellent renal function with our double balloon catheter system. Compared with donor Cr levels, eGFR and 1-hour biopsy could be useful for donor evaluation and transplant renal function.

Hypothermic or normothermic abdominal regional perfusion in high-risk donors with extended warm ischemia times: impact on outcomes?

Donation after circulatory determination of death (DCD) has the potential to increase the applicability of transplantation as a treatment for end-stage organ disease; its use is limited, however, by the warm ischemic damage suffered by potential grafts. Abdominal regional perfusion (ARP) has been employed in this setting to not only curtail the deleterious effects of cardiac arrest by re-establishing oxygenated flow but also test and even improve the viability of the kidneys and liver prior to transplantation. In the present review article, we discuss experimental and clinical studies that have been published to date on the use of ARP in DCD, differentiating between its application under hypothermic and normothermic conditions. In addition to describing results that have been achieved thus far, we describe the major obstacles limiting the broader implementation of ARP in this context as well as potential means for improving the effectiveness of this modality in the future.

Cardiac Transplantation Using Hearts from Donation after Circulatory Death (Dcd) Donors – A Viable Source of Organs?

Purpose Use of DCD donors for heart transplantation is limited by fear of warm ischaemic damage. We aim to investigate the impact of varying periods of warm ischaemia (WI) on cardiac function, and evaluate pharmacological post-conditioning strategies to limit ischaemic injury. Methods and Materials In a porcine DCD asphyxia model, 3 warm ischaemic times (WIT) were evaluated. Hearts were flushed with Celsior post WI. Pharmacological post-conditioning was instituted through supplementation of Celsior ( table 1 ). Hearts were explanted onto an isolated working heart circuit & performance assessed for 4 hours - functional (Cardiac Output, Coronary Flow), metabolic (pH, lactate, myocardial oxygen consumption), and biochemical parameters of myocardial injury (troponin, LDH) were evaluated. Results Compared to control hearts, Group 1 showed complete functional recovery, Group 2 partial recovery & Group 3 minimal recovery. Group 2 had higher lactate levels (p=0.03) and troponin release (p=0.03) than Group 1. Following supplementation (Group 2S), there was improved recovery (c/w group 2), with superior CO (p=0.01), higher coronary flows (p=0.01), decreased troponin release (p=0.05), less oedema (p=0.03), all comparable to control hearts levels. Improvement also occurred between group 3 and 3S. Conclusions Hearts with a WIT of Table 1 Group n = WIT (mins) Preservation Solution (Supplementation = addition of gyceryl trinitrate, erythropoietin and zoniporide) Control 6 - Celsior Group 1 6 15-20 Celsior Group 2 6 30 Celsior Group 2S 6 30 Celsior - supplemented Group 3 3 40 Celsior Group 3S 3 40 Celsior - supplemented

Mild hypothermia during global cardiac ischemia opens a window of opportunity to develop heart donation after cardiac death

Although heart donation after cardiac death (DCD) could greatly improve graft availability, concerns regarding warm ischemic damage typically preclude transplantation. Improving tolerance to warm ischemia may thus open a window of opportunity for DCD hearts. We investigated the hypothesis that, compared with normothermia, mild hypothermia (32°C) initiated after ischemic onset improves cardiac functional recovery upon reperfusion. Isolated, working hearts from adult, male Wistar rats underwent global, no-flow ischemia, and reperfusion (n=28). After ischemic onset, temperature was maintained at either 37°C for 20 or 30min or reduced to 32°C for 40, 50, or 60min. Recovery was measured after 60-min reperfusion. Following normothermic ischemia, recovery of rate-pressure product (RPP; per cent of preischemic value) was almost complete after 20-min ischemia (97±9%), whereas no recovery was detectable after 30-min ischemia. After mildly hypothermic ischemia (32°C), RPP also recovered well after 40min (86±4%). Markers of metabolism and necrosis were similar in 37°C/20min and 32°C/40min groups. Simple reduction in cardiac temperature by a few degrees after the onset of global ischemia dramatically prolongs the interval during which the heart remains resistant to functional deterioration. Preservation of hemodynamic function is associated with improved metabolic recovery and reduced necrosis. The application of mild hypothermia may be a simple first step towards development of clinical protocols for DCD heart recovery.

Evaluation of 18F-Fluorodeoxyglucose Labeled Fresh Islets and Warm Ischemic Islets Survival after Transplantation with Positron Emission Tomography

Objective: In recent years, the use of positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) labeled islets has been considered to be a potential modality to visualize islet transplantation. This modality is helpful to quantify early engraftment of islet transplantation. The objective of this study was to evaluate the early islets survival of the FDG labeled islets with or without warm ischemic damage, that were transplanted into the liver using a PET. Methods: Islets were isolated from Lewis rat pancreata with or without 30-minute warm ischemia times (WIT). For islets' labeling, 300 islets were incubated with 3MBq FDG for 60 minutes. FDG-labeled syngeneic fresh islets or WIT islets were transplanted into the liver via portal vein. In in vivo study, a dynamic PET scan of the liver was started at the end of islet transplantation and scanned for 90 minutes. The FDG uptake was expressed liver% injection dose (ID). In ex vivo study, the liver was exposed to a imaging plate for 30 minutes and the imaging plate was scanned with laser biomolecular imager for single fluorescence autoradiography. Results: In the PET study, FDG labeled islets ware visualized and were shown as the heterogeneous hot spots in the liver. The liver% ID of the fresh islets was 27.8 and that of the WIT islets was 20.1 at the end of islet transplantation. At 90 minutes after transplantation, the liver% ID was decreased to 14.7 in the fresh islets and 10.1 in the WIT islets 10.1. In the autoradiogram, the numbers of hot spots were more obviously visualized in the liver with the fresh islets than in the liver with the WIT islets. Conclusion: Our study demonstrated that almost 50% of the islets were immediately lost in both the fresh islets and the WIT islets transplantation at 90 minutes after transplantation. Islet survival, however, was 1.4 times higher in the fresh islets than that in the WIT islets in the early engraftment phase. The positron emission tomography (PET) with 18F-fluorodeoxyglucose (FDG) labeled islets may be a potent modality to evaluate and quantify the successful clinical islets transplantation.

Assessment of eGFR and One-Hour Biopsy in Living-Related and Deceased Kidney Transplants with Using In-Situ-Cooling Double-Balloon Catheters

Introduction: The worldwide shortage of deceased donor kidneys for transplantation has become a serious issue in the past decade and marginal donor kidneys have been studied. However, both availability and feasibility of marginal deceased donor kidneys are still problematic. Some kidney donor candidates have been rejected because of increased creatinine(Cr) levels prior to death, while some transplants have had good renal function in spite of the high Cr levels of the donors. In order to reduce the discarded donor kidney rate, we performed specially designed in-situ cooling system. The aim of the present study was to estimate availability of deceased donor kidney with using our in-situ-cooling system, analyze donor one-hour biopsy, and find better evaluation method to estimate donor kidney function rather than using donor Cr, comparing with living related transplants. Methods: We studied 129 deceased renal transplant recipients (DD) who received kidneys from non-heart-beating donors beginning in 1984. Calcineurin Inhibitors were given to all transplants. Donors were in Maastricht Donor Categories III and IV and to minimize warm ischemic kidney damage we performed in situ cooling with specially designed double-balloon catheters. One-hour biopsies were analyzed with Remuzzi's evaluation system, and were scored for glomerulosclerosis, tubular atrophy, interstitial fibrosis and vascular narrowing. Twenty-nine living-related transplants (LD) were a control group. Results: In the DD group average donor Cr and eGFR levels at admission were 0.3-2.1 mg/dl (ave. 1.0) and 24-138 ml/min/1.73 (ave. 67) and levels before death were 0.3-15.9 (2.7) and 4-164 (34). Average recipient Cr and eGFR levels at discharge were 0.3-5.3 (1.8) and .10-133 (39). Although average donor Cr levels before death were high, the DD had good function using our catheter system. To define kidney function after transplant, the DD were classified according to recipient eGFR at discharge: < 25 ml/min/1.73 for the poor function group (PF: n=32) and >25 for the good function group (GF: n=95). GF had higher eGFR levels at donor hospital admission than the PF (p=0.005). There was no statistically significant difference in Cr levels of donor (at admission and before death) between those groups. Pathologically, the DD with less glomerular sclerosis of 1-hour biopsies had better graft survival than damaged subjects (p=0.015). Other histological scores were not associated with kidney survival. In mild-damaged histological scores, discharge-eGFR levels of DD and LD were the same with no statistically significant difference, although DD had poorer function than LD in less-damaged scores. Conclusions: Deceased kidney transplants had excellent renal function with our double balloon catheter system. Donor Cr levels were not a useful measurement for our analysis, but eGFR and 1-hour biopsy should be used for donor evaluation and transplant renal function.

Hearts from Donations after Circulatory Death (DCD) Donors - Ischaemic Post-Conditioning Significantly Improves Recovery of Cardiac Function Following Warm Ischaemia in A Porcine Model

Introduction: Utilisation of hearts from Donations after circulatory death (DCD) donors has been limited by fear of warm ischaemic damage. We aim to investigate the impact of varying periods of warm ischaemia on cardiac function in DCD hearts, and evaluate ischaemic post-conditioning strategies to limit warm ischaemic injury. Methods: Utilising a porcine DCD model, 3 warm ischaemic time (WIT) periods were evaluated. All hearts were antegrade flushed with Celsior solution after the designated period of warm ischaemia. Ischaemic post-conditioning was affected with the supplementation of Celsior with glyceryl trinitrate (GTN), erythropoietin (EPO), and zoniporide - this approach has been studied extensively in our laboratory1. (table 1)Hearts were explanted onto an isolated working heart circuit. Left heart performance was assessed for 4 hours - functional assessment (Cardiac Output, Coronary Flow, Left Atrial Pressure (LAP) vs Aortic Flow (AF) challenge), metabolic recovery (pH, lactate, myocardial oxygen consumption), and biochemical parameters (troponin, LDH) were evaluated. Results: When compared with control hearts, Group 1 hearts showed complete functional recovery, Group 2 had partial recovery and Group 3 had no recovery. Cardiac Output was inferior with Group 2 hearts (graph 1). The increase in AF in response to increased LAP was significantly blunted for Group 2 (p=0.05), when compared with control and Group 1. Group 2 hearts also remained more acidotic (p=0.03), had higher lactate levels (p=0.03), greater troponin release (p=0.03) and had non-significant trends towards higher LDH levels than control or Group 1 hearts. Following the supplementation of the preservation flush for 30 minute warm ischaemia hearts (Group 4) there was a significantly improved functional and biochemical recovery when compared with group 2 hearts (unsupplemented 30 minute warm ischaemia hearts). Comparing group 2 and group 4, group 4 had superior Cardiac Output (p < 0.01, see graph 1), higher coronary flows (p < 0.01), superior performance in the AF vs LAP challenge (p = 0.03), and decreased troponin release (p=0.05).Figure: [Graph 1]Conclusion: Hearts with a WIT of less than 20 minutes demonstrate excellent recovery, supporting the potential for DCD hearts in transplantation. The detrimental effects of warm ischaemia become evident beyond 20 minutes - here, ischaemc post-conditioning strategies aimed at mitigating ischaemia-reperfusion injury significantly improve cardiac recovery. With the utilization of such strategies in preserving cardiac function following 30 minutes of warm ischaemia, the potential for translation to clinical DCD heart transplantation is greatly strengthened and warrants further investigation.

2266 ASSESSMENT OF EGFR AND ONE-HOUR BIOPSY USING IN-SITU-COOLING DOUBLE-BALLOON CATHETERS IN DECEASED KIDNEY TRANSPLANTS

You have accessJournal of UrologyTransplantation & Vascular Surgery: Renal Transplantation, Vascular Surgery II1 Apr 20122266 ASSESSMENT OF EGFR AND ONE-HOUR BIOPSY USING IN-SITU-COOLING DOUBLE-BALLOON CATHETERS IN DECEASED KIDNEY TRANSPLANTS Kazuo Mizutani, Ryohei Hattori, Tsuneo Kinukawa, Osamu Kamihira, and Momokazu Gotoh Kazuo MizutaniKazuo Mizutani Nagoya, Aichi, Japan More articles by this author , Ryohei HattoriRyohei Hattori Nagoya, Japan More articles by this author , Tsuneo KinukawaTsuneo Kinukawa Nagoya, Japan More articles by this author , Osamu KamihiraOsamu Kamihira Komaki, Japan More articles by this author , and Momokazu GotohMomokazu Gotoh Nagoya, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2444AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES The shortage of deceased donor kidneys for transplantation has become a worldwide issue in the past decades. However, both availability and feasibility of marginal deceased donor kidneys are still problematic. To increase donor pool and improve results, we created a specially designed in-situ cooling system. The purpose of this study was to estimate availability of deceased donor kidneys, analyze donor one-hour biopsy, and better evaluate methods to estimate donor/recipient kidney function other than using donor Cr, comparing with living related transplants. METHODS We studied 129 deceased renal transplant recipients (DD) who received kidneys from non-heart-beating donors beginning in 1984. Calcineurin Inhibitors were given to all transplants. Donors were in Maastricht Donor Categories III and IV and to minimize warm ischemic kidney damage we performed in situ cooling with specially designed double-balloon catheters. One-hour biopsies were analyzed with Remuzzi's evaluation system, and were scored for histological assessment. Twenty-nine living-related transplants (LD) were a control group. RESULTS In the DD group average donor Cr and eGFR levels at admission were 0.3-2.1mg/dl (ave. 1.0) and 24-138 ml/min/1.73 (ave. 67) and levels before death were 0.3-15.9 (2.7) and 4-164 (34). Average recipient Cr and eGFR levels at discharge were 0.3-5.3 (1.8) and .10-133 (39). Although average donor Cr levels before death were high, the DD had good function using our catheter system. To define kidney function after transplant, the DD were classified according to recipient eGFR at discharge: <25 ml/min/1.73 for the poor function group (PF: n=32) and >25 for the good function group (GF: n=95). GF had higher eGFR levels at donor hospital admission than the PF (p=0.005). There was no statistically significant difference in Cr levels of donor (at admission and before death) between those groups. Pathologically, the DD with less glomerular sclerosis of 1-hour biopsies had better graft survival than damaged subjects (p=0.015). Other histological scores were not associated with kidney survival. In mild-damaged histological scores, discharge-eGFR levels of DD and LD were the same with no statistically significant difference, although DD had poorer function than LD in less-damaged scores. CONCLUSIONS Deceased kidney transplants had excellent renal function with our double balloon catheter system. Donor Cr levels were not a useful measurement for our analysis, but eGFR and 1-hour biopsy should be used for donor evaluation and transplant renal function. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e914 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazuo Mizutani Nagoya, Aichi, Japan More articles by this author Ryohei Hattori Nagoya, Japan More articles by this author Tsuneo Kinukawa Nagoya, Japan More articles by this author Osamu Kamihira Komaki, Japan More articles by this author Momokazu Gotoh Nagoya, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Donation after circulatory death – a new role for the anaesthetist?

Donation after circulatory death – a new role for the anaesthetist?