Critical warm ischemia time point for cardiac donation after circulatory death.
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ABSTRACT:
SUBMITTER: Sanchez-Camara S
PROVIDER: S-EPMC9303247 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The ultimate treatment for patients with end-stage heart failure is heart transplantation. The number of donor hearts which are primarily procured from donation after brain death (DBD) donors is limited, but donation after circulatory death (DCD) donor hearts can increase the heart donor pool. However, ischemia and reperfusion injuries associated with the DCD process causes myocardial damage, limiting the use of DCD hearts in transplantation. Addressing this problem is critical in the exploration of DCD hearts as suitable donor hearts for transplantation. In this study, rat hearts were procured following the control beating-heart donor (CBD) or DCD donation process. Changes in mitochondria and cardiac function from DCD hearts subjected to 25 or 35 minutes of ischemia followed by 60 minutes of reperfusion were compared to CBD hearts. Following ischemia, rates of oxidative phosphorylation and calcium retention capacity were progressively impaired in DCD hearts compared to CBD hearts. Reperfusion caused additional mitochondrial dysfunction in DCD hearts. Developed pressure, inotropy and lusitropy, were significantly reduced in DCD hearts compared to CBD hearts. We, therefore, suggest that interventional strategies targeted before the onset of ischemia and at reperfusion could protect mitochondria, thus potentially making DCD hearts suitable for heart transplantation.
| S-EPMC7769461 | biostudies-literature
Project description:Dr. O.P. Yadava, CEO and Chief Cardiac Surgeon, National Heart Institute, New Delhi, India, and Editor-in-Chief, Indian Journal of Thoracic and Cardiovascular Surgery, in a conversation with Dr. Catherine Dushyant Sudarshan, discusses the state of donation after circulatory death for cardiac transplant and how it can address the donor shortages.
| S-EPMC7538526 | biostudies-literature
Project description:ObjectivesTo determine whether hearts reanimated with normothermic regional perfusion (NRP) have clinically detectable changes in function using echocardiography comparing the prearrest and post-NRP imaging. As heart transplantation from donation after circulatory death (DCD) continues to increase, preliminary results suggest outcomes comparable with donation after brain death. It is unknown whether the obligatory period of warm ischemia experienced during DCD withdrawal process causes immediate changes in cardiac allograft function following in situ reanimation.MethodsWe retrospectively reviewed and compared predonation with postreanimation echocardiographic findings in all DCD donors at our institution from January to October 2021. All DCD donor organs were reanimated with in situ thoracoabdominal NRP after circulatory death. Echocardiographic assessment included (1) 2-dimensional and speckle-tracking measures of chamber size and function; (2) ejection fraction; (3) fractional area change; and (4) global longitudinal strain.ResultsAltogether, 4 DCD heart donations were performed during the study period. Basic demographics and withdrawal ischemic time periods are reported. There were no changes in left ventricular ejection fraction and right ventricular fractional area change when comparing the predonation and the postreanimation echocardiogram. There was a minimal, nonstatistically significant decrease in left ventricular global longitudinal strain and right ventricular free-wall systolic strain in 3 of the 4 donors following reanimation.ConclusionsDCD cardiac allografts reanimated with NRP demonstrated no change in echocardiographic parameters used for a standard predonation donor heart evaluation. Findings suggest cardiac function of DCD allografts reanimated with thoracoabdominal NRP is not adversely impacted by limited period of warm ischemia following circulatory arrest.
| S-EPMC9579788 | biostudies-literature
Project description:Transplantation of any organ into a recipient requires a donor. Lung transplant has a long history of an inadequate number of suitable donors to meet demand, leading to deaths on the waiting list annually since national data was collected, and strict listing criteria. Before the Uniform Determination of Death Act (UDDA), passed in 1980, legally defined brain death in the U.S., all donors for lung transplant came from sudden death victims [uncontrolled Donation after Circulatory Death donors (uDCDs)] in the recipient's hospital emergency department. After passage of the UDDA, uDCDs were abandoned to Donation after Brain Death donors (DBDs)-perhaps prematurely. Compared to livers and kidneys, many DBDs have lungs that are unsuitable for transplant, due to aspiration pneumonia, neurogenic pulmonary edema, trauma, and the effects of brain death on lung function. Another group of donors has become available-patients with a devastating irrecoverable brain injury that do not meet criteria for brain death. If a decision is made by next-of-kin (NOK) to withdraw life support and allow death to occur by asphyxiation, with NOK consent, these individuals can have organs recovered if death occurs relatively quickly after cessation of mechanical ventilation and maintenance of their airway. These are known as controlled Donation after Circulatory Death donors (cDCDs). For a variety of reasons, in the U.S., lungs are recovered from cDCDs at a much lower rate than kidneys and livers. Ex-vivo lung perfusion (EVLP) in the last decade has had a modest impact on increasing the number of lungs for transplant from DBDs, but may have had a larger impact on lungs from cDCDs, and may be indispensable for safe transplantation of lungs from uDCDs. In the next decade, DCDs may have a substantial impact on the number of lung transplants performed in the U.S. and around the world.
| S-EPMC8662509 | biostudies-literature
Project description:We conducted a prospective observational study on 100 consecutive patients admitted to intensive care units at Leeds General Infirmary following out-of-hospital cardiac arrest. In the non-survivors, we reviewed their potential for organ donation via donation after circulatory death. Out of the 100 patients, 53 did not survive to hospital discharge. Out of these non-survivors, 13 died very suddenly within the intensive care unit and 3 other patients subsequently died in a general ward following discharge from the intensive care unit. One patient became brainstem dead, with out-of-hospital cardiac arrest secondary to a subarachnoid haemorrhage, rather than a primary cardiac cause. This patient went on to donate via the brain death mode. The remaining 36 patients had treatment withdrawn in the intensive care unit. Of these, 29 were referred to the transplant team for potential donation after circulatory death, and 14 were deemed to be medically suitable for organ donation. However, the families of only seven agreed to proceed with the donation process. Of these seven, only one went on to donate, primarily because the majority did not die within the 3-h window for acceptable warm ischaemia. In this series, the potential for donation after circulatory death following out-of-hospital cardiac arrest was limited. We would suggest an open dialogue between intensive care unit staff and transplant teams about the realistic potential for organ donation in each case. When clinicians believe it is unlikely that donation after circulatory death will proceed due to a failure to die within the pre-requisite time, then not starting with the donation after circulatory death process should be seriously considered.
| S-EPMC5606394 | biostudies-literature
Project description:ObjectiveDespite growing evidence of comparable outcomes in recipients of donation after circulatory death and donation after brain death donor lungs, donation after circulatory death allografts continue to be underused nationally. We examined predictors of nonuse.MethodsAll donors who donated at least 1 organ for transplantation between 2005 and 2019 were identified in the United Network for Organ Sharing registry and stratified by donation type. The primary outcome of interest was use of pulmonary allografts. Organ disposition and refusal reasons were evaluated. Multivariable regression modeling was used to assess the relationship between donor factors and use.ResultsA total of 15,458 donation after circulatory death donors met inclusion criteria. Of 30,916 lungs, 3.7% (1158) were used for transplantation and 72.8% were discarded primarily due to poor organ function. Consent was not requested in 8.4% of donation after circulatory death offers with donation after circulatory death being the leading reason (73.4%). Nonuse was associated with smoking history (P < .001), clinical infection with a blood source (12% vs 7.4%, P = .001), and lower PaO2/FiO2 ratio (median 230 vs 423, P < .001). In multivariable regression, those with PaO2/FiO2 ratio less than 250 were least likely to be transplanted (adjusted odds ratio, 0.03; P < .001), followed by cigarette use (0.28, P < .001), and donor age >50 (0.75, P = .031). Recent transplant era was associated with significantly increased use (adjusted odds ratio, 2.28; P < .001).ConclusionsNontransplantation of donation after circulatory death lungs was associated with potentially modifiable predonation factors, including organ procurement organizations' consenting behavior, and donor factors, including hypoxemia. Interventions to increase consent and standardize donation after circulatory death donor management, including selective use of ex vivo lung perfusion in the setting of hypoxemia, may increase use and the donor pool.
| S-EPMC7647952 | biostudies-literature
Project description:While donation after circulatory death (DCD) has expanded options for organ donation, many who wish to donate are still unable to do so. We conducted face-to-face interviews with family members (N = 15) who had direct experience with unsuccessful DCD and 5 focus groups with professionals involved in the donation process. We used qualitative content analysis to characterize the harms of nondonation as perceived by participants. Participants reported a broad spectrum of harms affecting organ recipients, donors, and donor families. Harms included waste of precious life-giving organs and hospital resources, inability to honor the donor's memory and character, and impaired ability for families to make sense of tragedy and cope with loss. Donor families empathized with the initial hope and ultimate despair of potential recipients who must continue their wait on the transplant list. Focus group members reinforced these findings and highlighted the struggle of families to navigate the uncertainty regarding the timing of death during the donation process. While families reported significant harm, many appreciated the donation attempt. These findings highlight the importance of organ donation to donor families and the difficult experiences associated with current processes that could inform development of alternative donation strategies.
| S-EPMC5790593 | biostudies-literature
Project description:BACKGROUND Ischemia/reperfusion injury (IRI) is an inherent problem in organ transplantation, owing to the obligate period of ischemia that organs must endure. Cyclosporine A (CsA), though better know as an immunosuppressant, has been shown to mitigate warm IRI in a variety of organ types, including the liver. However, there is little evidence for CsA in preventing hepatic IRI in the transplant setting. MATERIAL AND METHODS In the present study, we tested the effect of CsA on hepatic IRI in a large-animal ex vivo model of donation after circulatory death (DCD). Porcine donors were pre-treated with either normal saline control or 20 mg/kg of CsA. Animals were subject to either 45 or 60 minutes of warm ischemia before hepatectomy, followed by 2 or 4 hours of cold storage prior to reperfusion on an ex vivo circuit. Over the course of a 12-hour perfusion, perfusion parameters were recorded and perfusate samples and biopsies were taken at regular intervals. RESULTS Peak perfusate lactate dehydrogenase was significantly decreased in the lower-ischemia group treated with CsA compared to the untreated group (4220 U/L [3515-5815] vs 11 305 [10 100-11 674]; P=0.023). However, no difference was seen between controls and CsA-treated groups on other parameters in perfusate alanine or asparagine aminotransferase (P=0.912, 0.455, respectively). Correspondingly, we found no difference on midpoint histological injury score (P=0.271). CONCLUSIONS We found minimal evidence that CsA is protective against hepatic IRI in our DCD model.
| S-EPMC10838008 | biostudies-literature
Project description:Normothermic regional perfusion (NRP) allows assessment of therapeutic interventions prior to donation after circulatory death transplantation. Sodium-3-hydroxybutyrate (3-OHB) increases cardiac output in heart failure patients and diminishes ischemia-reperfusion injury, presumably by improving mitochondrial metabolism. We investigated effects of 3-OHB on cardiac and mitochondrial function in transplanted hearts and in cardiac organoids. Donor pigs (n = 14) underwent circulatory death followed by NRP. Following static cold storage, hearts were transplanted into recipient pigs. 3-OHB or Ringer's acetate infusions were initiated during NRP and after transplantation. We evaluated hemodynamics and mitochondrial function. 3-OHB mediated effects on contractility, relaxation, calcium, and conduction were tested in cardiac organoids from human pluripotent stem cells. Following NRP, 3-OHB increased cardiac output (P < 0.0001) by increasing stroke volume (P = 0.006), dP/dt (P = 0.02) and reducing arterial elastance (P = 0.02). Following transplantation, infusion of 3-OHB maintained mitochondrial respiration (P = 0.009) but caused inotropy-resistant vasoplegia that prevented weaning. In cardiac organoids, 3-OHB increased contraction amplitude (P = 0.002) and shortened contraction duration (P = 0.013) without affecting calcium handling or conduction velocity. 3-OHB had beneficial cardiac effects and may have a potential to secure cardiac function during heart transplantation. Further studies are needed to optimize administration practice in donors and recipients and to validate the effect on mitochondrial function.
| S-EPMC10774377 | biostudies-literature
Project description:BackgroundDonation after circulatory death (DCD) liver transplantation (LT) has become an effective mechanism for expanding the donor pool and decreasing waitlist mortality. However, it is unclear if low-volume DCD centers can achieve comparable outcomes to high-volume centers.MethodsFrom 2011 to 2019 utilizing the United Network for Organ Sharing (UNOS) database, liver transplant centers were categorized into tertiles based on their annual volume of DCD LTs. Donor selection, recipient selection, and survival outcomes were compared between very-low volume (VLV, n = 1-2 DCD LTs per year), low-volume (LV, n = 3-5), and high-volume (HV, n > 5) centers.ResultsOne hundred and ten centers performed 3273 DCD LTs. VLV-centers performed 339 (10.4%), LV-centers performed 627 (19.2%), and HV-centers performed 2307 (70.4%) LTs. 30-day, 90-day, and 1-year patient and graft survival were significantly increased at HV-centers (all P < .05). Recipients at HV-centers had shorter waitlist durations (P < .01) and shorter hospital lengths of stay (P < .01). On multivariable regression, undergoing DCD LT at a VLV-center or LV-center was associated with increased 1-year patient mortality (VLV-OR:1.73, 1.12-2.69) (LV-OR: 1.42, 1.01-2.00) and 1-year graft failure (VLV-OR: 1.79, 1.24-2.58) (LV-OR: 1.28, .95-1.72).DiscussionIncreased annual DCD liver transplant volume is associated with improved patient and graft survival.
| S-EPMC9287056 | biostudies-literature