Heart-beating Donors Research Articles

Effects of exogenous surfactant on the non‐heart‐beating donor lung graft in experimental lung transplantation – a stereological study

The use of non-heart-beating donor (NHBD) lungs may help to overcome the shortage of lung grafts in clinical lung transplantation, but warm ischaemia and ischaemia/reperfusion injury (I/R injury) resulting in primary graft dysfunction represent a considerable threat. Thus, better strategies for optimized preservation of lung grafts are urgently needed. Surfactant dysfunction has been shown to contribute to I/R injury, and surfactant replacement therapy is effective in enhancing lung function and structural integrity in related rat models. In the present study we hypothesize that surfactant replacement therapy reduces oedema formation in a pig model of NHBD lung transplantation. Oedema formation was quantified with (SF) and without (non-SF) surfactant replacement therapy in interstitial and alveolar compartments by means of design-based stereology in NHBD lungs 7 h after cardiac arrest, reperfusion and transplantation. A sham-operated group served as control. In both NHBD groups, nearly all animals died within the first hours after transplantation due to right heart failure. Both SF and non-SF developed an interstitial oedema of similar degree, as shown by an increase in septal wall volume and arithmetic mean thickness as well as an increase in the volume of peribron-chovascular connective tissue. Regarding intra-alveolar oedema, no statistically significant difference could be found between SF and non-SF. In conclusion, surfactant replacement therapy cannot prevent poor outcome after prolonged warm ischaemia of 7 h in this model. While the beneficial effects of surfactant replacement therapy have been observed in several experimental and clinical studies related to heart-beating donor lungs and cold ischaemia, it is unlikely that surfactant replacement therapy will overcome the shortage of organs in the context of prolonged warm ischaemia, for example, 7 h. Moreover, our data demonstrate that right heart function and dysfunctions of the pulmonary vascular bed are limiting factors that need to be addressed in NHBD.

A Biblical Approach to Cadaveric Organ Transplants

Upon passing their driver’s license exam every American has the opportunity to become an organ donor. Organ donor status allows immediate retrieval of transplantable organs after death for transplantation into other patients in order to save their lives. Many citizens endorse this action because one donor can save multiple lives by donating viable organs postmortem. However, some people do not endorse organ transplants arguing that it violates the body and that being an organ donor results in a premature declaration of death. The current standard for cadaveric transplantation is retrieval from heart beating donors. A heart beating donor is brain dead with circulation artificially maintained by a ventilator. The ethical permissibility of this standard is questioned by some Christians. Christians do not believe in a bodily resurrection which provides one basis for permitting organ transplants. Christians also view the body as having intrinsic worth because of the presence of the image of God. When one views bodies as having intrinsic worth organ donation becomes a natural logical conclusion supported by stewardship and loving others (Richards, 2012). While there is nothing inherently wrong with giving of receiving cadaveric organs ethical discussions still remain. Transplantation of cadaveric organs raises ethical questions about the dying process, defining death, and bodily integrity (Ramsey, 2002). The best way to evaluate these ethical issues is by establishing a Biblical framework through which to consider and evaluate them. This paper will perform that task, ultimately arguing for the support of cadaveric transplants by Christians as an exercise of stewardship practiced in a way that maintains the sanctity of life.

Forensic Aspect of Mechanical Ventilation in Intensive Care Unit

Facing a medicolegal problem while serving in a govt. or semi govt. or private hospital has become a headache for medical professionals. It may be in the form of civil or criminal or corporate or composite negligence. Problems arising from treatment in intensive care unit are a recent edition in this regard. Death of a patient in ICU, organ transplantation from a beating heart donor may bring charge of negligence against the doctor, nurse, hospital staffs and authority. Here we have tried to focus on this aspect medicolegal disputes and the way to overcome these problems in short.

Impact of static cold storage VS hypothermic machine preservation on ischemic kidney graft: inflammatory cytokines and adhesion molecules as markers of ischemia/reperfusion tissue damage. Our preliminary results

AbstractAt the present time, deceased heart-beating donor kidney allografts are usually stored cold. Extended-criteria donor (ECD) grafts show higher sensitivity to ischemia–reperfusion damage than standard kidneys. The increasing use of marginal organs in clinical transplantation urgently requires a more effective preservation system. Pulsatile hypothermic machine perfusion has shown major advantages over static cold storage in terms of reduced organ injury during preservation and improved early graft function. This preliminary study aims to compare pulsatile hypothermic machine perfusion and static cold storage of kidney allografts, outlining differences in the levels of early inflammatory cytokines (TNF-α, IL-2 and IL-1β) and soluble intracellular adhesion molecule (sICAM-1) in perfusion and preservation liquid.

Obstacles of Non–heart-beating Donor Kidney Transplantation in Japan to Date and Future Perspectives

In Japan, multiple organ retrieval from brain-dead heart-beating donors has been gradually increasing since the law was adopted in 1997 and amended in 2009. However, almost more than 90% of total deceased donor kidney transplantation (DDKT) in Japan are still obtained from non–heart-beating donors (NHBD). The majority of NHBD are Maastricht categories IV and III. In category IV, we usually place a double balloon arterial and a venous drainage catheter via the femoral vessels after the diagnosis of clinical brain death and acquisition of informed consent from the family. After controlled cardiac arrest, the double balloons are inflated and in situ cold perfusion started as soon as possible to minimize warm ischemic time (WIT), seeking to achieve a zero to within a few minutes WIT in most cases. In category III, it is impossible to place the device prior to cardiac arrest. In these cases, after declaration of cardiac death, cardiopulmonary compression is accompanied by systemic heparinization, immediate laparotomy, and insertion of a cold perfusion catheter at the aortic and caval bifurcations to minimize WIT. NHBD kidney retrieval is critical; extirpation must be performed as rapidly as possible. The results of NHBD kidney transplantation in Japan are excellent, according to the advancement and utilization of in situ cannulation, organ perfusion, and sophisticated retrieval techniques. The patient and graft survival rates of DDKT at 1, 3, and 5 years in most recent 2001 to 2007 era were 95.4%, 92.2%, 89.1% (n = 945) and 89.2%, 83.7%, 77.8% (n = 919), respectively.

Organ donation in the UK: how general practice can help

Solid organ transplantation not only dramatically improves the length and quality of life of the recipients but also saves the NHS money.1,2 Organs routinely transplanted include heart, lung, liver, pancreas, and bowel but other organs that may be transplanted include thymus, hand, face, leg, abdominal wall, and uterus. The last two decades have seen major changes in organ transplantation: developments in surgery, anaesthesia, interventional radiology, microbiology, and pharmacology have transformed what many still today believe is a high intensity, high risk procedure with a high mortality to a routine procedure with low morbidity and a high long-term success rate. As the number of patients undergoing and surviving transplantation increases, GPs will see increasing numbers. However, transplantation activity is limited by donor availability. Organ donors may be living or deceased. Living organ donation is regulated across the UK by the Human Tissue Authority which ensures that donation is done ethically, legally, and without financial or other inducement. Most living donations are directed to a named recipient (usually a family member or close friend) but we are seeing a small but increasing number of altruistic donors who donate to strangers. Living donation is not devoid of risk to the donor: the risk of death for a kidney donor is of the order of 1 in 4000 but for a living liver donor, the risk of death is about 1 in 250. Deceased donation may occur after brain death (DBD; previously known as heart beating donors) or after circulatory death (DCD). A decade ago, the UK was very firmly in the lower ranking for organ donation (with donor rates of 12.0 per million population (pmp) in 2003 (Figure 1 …

Heparin does not seem to improve the function of pulmonary grafts for lung transplantation

Background. It has been debated whether or not heparin infusion before or after non-heart-beating donors are declared dead improves the quality of pulmonary grafts. In clinical lung transplantation with heart-beating donors (HBDs) heparin is routinely infused prior to organ harvesting since it is believed to improve pulmonary grafts by minimizing thrombosis formation in the pulmonary grafts. Here, we raise the question of whether or not the use of heparin in HBDs improves the quality of the pulmonary grafts. Methods. Twelve landrace pigs were divided into two groups of six animals; heparin was given prior to lung harvesting in one group, while the other group did not receive any heparin. The lungs were evaluated using an ex vivo lung perfusion (EVLP) method. Results. No significant difference in arterial oxygen partial pressure (PaO2) was observed between the two groups at an inspired oxygen fraction (FiO2) of 1.0 (mean 69.2 kPa, range 46.1–77.0 in the non-heparin group, and 61.6 kPa, range 47.9–71.4 in the heparin group, p = 0.44), neither in pulmonary vascular resistance: mean 543 ((dyne × s)/cm5) (range 280–615) in the non-heparin group and 533 ((dyne × s)/cm5) (320–762) in the heparin group (p = 0.99). Conclusions. Heparin did not seem to improve pulmonary graft function in our animal model using conventional HBDs.

Improvement of Hepatocyte Recovery From Rat Liver Subjected to 1-Hour Warm Ischemic Injury by Using Citrate Phosphate Dextrose Added to Euro-Collins Perfusion Solution

Warm ischemia (WI)-related injury interferes with recovery of primary hepatocyte after collagenase digestion of surgically resected or non–heart-beating donor livers as human cell sources. We speculated that digestion is impaired due to reduced microcirculation, caused by microembolism after WI. We sought to improve hepatocyte recovery after WI using a rat model. Anesthetized 9-week-old male Sprague-Dawley rats underwent a midline abdominal incision to insert a 22-gauge cannula into the portal vein. WI was initiated by ligating both the cannula and the hepatic artery. We compared Euro-Collins (EC) perfusion solution with 2 anticoagulants—heparin or citrate phosphate dextrose (CPD)—versus ethylene glycol tetraacetic acid (EGTA) combined with Ca2+− and Mg2+-free Hank's solution (CM-free Hank's solution). Use of CM-free Hank's solution yielded only 0.75 ± 0.15 × 108 and 0.82 ± 0.20 × 108 cells at 30 and 60 minutes WI respectively. However, CPD, but not heparin, added to the EC solution produced the best cell recovery (CPD: 2.15 ± 0.38 × 108; heparin: 1.63 ± 0.31 × 108). During macroscopic observation, CPD added to EC solution also demonstrated best blood flushing. CPD added to EC solution achieved greater hepatocyte recovery than CM-free Hank's solution by restoring microcirculation during flushing of blood from liver tissue subjected to WI.

The incidence of potential missed organ donors in intensive care units and emergency rooms: a retrospective cohort

There is a shortage of organ donors in Canada. The number of potential organ donors that are not referred to organ procurement organizations in Canada is unknown. We conducted a retrospective cohort study of all deaths in ICUs and emergency rooms not referred to the Human Organ Procurement and Exchange Program in four hospitals between 1 January 2008 and 31 December 2010. The primary outcome was the number of normal and expanded criteria heart-beating donors and circulatory death (DCD) donors. Of 2,931 deaths, 64 patients were identified as having a high probability for progression to heart-beating donation (Glasgow Coma Score of 3 and three or more absent brainstem reflexes) and 130 patients were assessed for possible DCD donation. The number of potential abdominal and lung heart-beating donors ranged from 3.2 to 7.5 and 0.5 to 2.7 per million population. The number of potential DCD abdominal and lung donors ranged from 3.9 to 6.5 and 2.7 to 4.3 per million population. Potential heart-beating abdominal (p=0.04) and lung (p=0.06) donors increased after legislation mandating donation discussion. Non-pupillary brainstem reflexes were documented in fewer than 60% of records. Life-sustaining treatment was withdrawn in 19 of 46 (41.3%) cardiac arrest patients not requiring high doses of vasoactive drugs within 24h. The number of heart-beating or DCD organ donors represented by missed referrals may represent up to 7.5 donors per million population. Improved documentation of brainstem reflexes and encouraging referral of patients suffering cardiac arrest to ICU specialists may improve donor numbers.

Kidneys From Donors With Incidental Renal Tumors

The increase in the prevalence of end-stage renal disease in developed countries and the shortage of deceased donors has made it necessary to increase the graft pool by means of several strategies, such as live donation, non-heart-beating donors, and expanded criteria donors. Frequently, and because of the increasing acceptance of older donors, we find a higher percentage of incidental renal masses in these donors as a result of the inherent epidemiology of this disease. These kidneys can be considered suitable grafts after bench surgery to remove the tumor. Retrospective analysis of donors with a diagnosis of incidental small renal mass before implantation and their corresponding recipients was performed between January 2007 and September 2012. All cases underwent an ex vivo tumorectomy with a preoperatory pathologic analysis. Recipients were followed up according to our standard renal tumor protocol. Eight donors with incidental renal mass were detected (four live and four deceased donors). The mean age was 47.8 years. Eleven transplantations were performed. Eight cases received the kidney after tumor exeresis, and three, the contralateral one. The recipient mean age was 53.8 years.The mean tumor diameter was 14.8 mm, with pathologic stages pT1a in seven cases and pT1b in one case (five clear cell renal carcinoma, two chromophobe type, and one lipoma). Surgical margins were negative. Mean follow-up was 32.34 months; none of the patients presented tumor recurrence, and all had correct renal function. Kidneys with small incidental tumors can be considered an option for kidney transplantation in selected patients.

A new liver graft preparation method for uncontrolled non-heart-beating donors, combining short oxygenated warm perfusion and prostaglandin E1

BackgroundTo resolve the shortage of donors associated with liver transplantation, the potential uncontrolled non-heart-beating donor (UNHBD) pool is expected to increase. However, warm ischemia-reperfusion injury leads to inferior survival in transplantation using the grafts from UNHBD compared with those from heart-beating donors. To overcome this problem, we developed a new method for preparation of liver grafts from UNHBDs consisting of a combination of short oxygenated warm perfusion (SOWP) and prostaglandin E1 (PGE1). MethodsUsing an ex vivo perfusion rat model, we examined the effectiveness of this new method. ResultsUsing SOWP and PGE1 treatment, the total amount of bile production during reperfusion in UNHBD grafts was increased to the same level as that in the heart-beating donor grafts. The addition of PGE1 to SOWP buffer decreased aspartate aminotransferase/alanine aminotransferase and tumor necrosis factor α levels during 1 h of reperfusion. Necrosis and apoptosis were significantly decreased by SOWP + PGE1 treatment. SOWP + PGE1 ameliorated induction of mitochondrial permeability transition, and the total amount of mitochondrial cytochrome c in the SOWP + PGE1 group after reperfusion was kept significantly higher than that in the no treatment group. Cytosolic c-Jun N-terminal protein kinase activation was significantly suppressed by SOWP + PGE1. Decrease in mitochondrial Bcl-2 was suppressed by SOWP alone and SOWP + PGE1 treatment, and Bax in the mitochondria was significantly suppressed by SOWP + PGE1. ConclusionSOWP and PGE1 prior to cold preservation significantly improved the function of liver grafts that underwent warm ischemia-reperfusion injury. Therefore, this method might be useful in liver transplantation using UNHBD grafts.

Routine Microbiologic Culture of Kidney Transport Fluid: A Single-Center Retrospective Study

BackgroundMicrobiologic culture of renal transplant fluid (RTF) has been performed since the 1950s and remained routine in some transplant centers. Although not evidence based, this conventional practice is relatively time consuming and costly. This single-center study sought to determine the prevalence and clinical significance of positive microbiologic cultures of RTF. MethodsData on RTF were collected retrospectively from renal transplant cases who had samples taken from RTF for microbiology from 2000 to 2006. Review of patient notes and microbiology reports identified positive results, time and type of antibiotic, posttransplantation development of sepsis, and any significant infection. ResultsOver the 6-year period we performed 370 renal transplantations from cadaveric or non–heart-beating donors. The living related or unrelated cases (n = 67) were excluded because we did not obtain RTF samples. Among the 303 remaining recipients, 237 (78%) had microscopy, culture, and sensitivity reports available. Positive cultures were identified in 66 patients, of whom 2% (n = 6) developed postoperative complications, including those related to organisms identified in the RTF in 3 patients. ConclusionsEarly identification of microorganisms, particularly in transplant patients, affects patient outcomes and quality of life. Routine screening of RTF for contamination allows for RTF-informed treatment of symptomatic patients after transplantation.

Extended Criteria Donors; a Safe Way To Expand the Lung Donor Pool?

Purpose Although the worldwide need to expand the lung donor pool, 75 % of multi-organ donors are discarded for lung transplantation (LTx). Herein, we report the outcome of liberalizing standard lung donor criteria. Methods and Materials All effective heart-beating lung donors within our hospital network between 2000 and 2010 (n=449) were classified as standard (SCD, n=284) or extended (ECD, n=149) criteria donors according to age (>55years), P/F ( Results Short-term outcome demonstrated significant differences in ICU stay ( p =0.03), PGD T12 ( p =0.003), T24 ( p =0.009) and T48 ( p =0.03) but not for time to extubation ( p =0.28). No significant differences were seen in long-term outcome like acute rejection ( p =0.84), chronic rejection ( p =0.18) and 10-year survival ( p =0.33, Figure A). Adding donor smoking status resulted in similar findings. Significant differences remained in short-term outcome like PGD T12( p =0.001), T24( p =0.001) and T48( p =0.001), extubation time ( p =0.04), ICU stay ( p =0.02) was observed. While no differences were found for long-term outcome as acute rejection ( P =0.85), chronic rejection ( p =0.54) and survival ( p =0.72, Figure B). Conclusions Although, transplanting ECD lungs has an impact on the early post-operative outcome after LTx, even more pronounced for lungs from smokers, liberalization of lung donor criteria did not negatively influence long-term outcome after LTx.

Épidémiologie de la transplantation rénale en France

Kidney transplantation activity in France is among the most important worldwide: in 2011, 2976 transplants have been performed (47.5 per million population), and the number of patients living with a functional graft is estimated around 30,000, representing 44.7% of all patients (n=67,270) treated for end-stage renal failure. However, the rate of preemptive kidney transplants remains very low, only 3.3% of incident patients starting renal replacement therapy. The analysis of demand showed a progressive increase in recent years, as demonstrated by the registration rate on the kidney transplantation waiting list, increasing by 5% yearly between 2006 and 2010, but with huge differences according to age categories and regional registration areas, reflecting discrepant appreciations in indications for kidney transplantation. The median waiting time between registration and transplantation increased progressively in recent years, reaching 22.3months with considerable variations according to regional areas and transplantation teams. Kidney transplantation activity, while increasing continuously, is far to cover the rising demand, and inexorably patients accumulate on the waiting list (around 9000 patients were registered by January 2012). This situation is the consequence of insufficient organ procurement activity. The deceased organ procurement rate remained high: 1572 harvested donors in 2011 (24.1 per million population), but the proportion of older donors rose in recent years, to reach the rate of 26% of donors older than 65years in 2011. The procurement activity of donors after cardiac arrest was reintroduced in 2006, but increased slowly: 65 transplants were performed in 2011 using kidney procured in non heart-beating donors. The living donor kidney transplantation activity has markedly increased recently: 302 living donor transplantations were performed in 2011, representing 10.1% of the kidney transplantations. Facing the predictable increase in the number of candidates, all efforts should be put together, by increasing the living donor transplantation activity and by supporting and promoting the deceased donor procurement activity.

Lung transplant of extrahospitalary donor after cardiac death

Non–heart-beating donors (NHBDs) have to meet the predefined criteria for organ donation including death from irreversible cessation of the beating heart. The Maastricht conference defined 4 NHBD categories to differentiate their viability and ethical-legal support. In Spain, NHBDs who originate from an out-of-hospital setting correspond to type II donors. These are patients who have had a cardiac arrest outside hospital and, after failed CPR attempts, are transferred with hemodynamic support measures to the hospital for organ donation. The Hospital Clínico San Carlos also has a lung donation program in collaboration with the Hospital Puerta de Hierro in Madrid and the Hospital Marques de Valdecilla in Santander. The objective of this study is to describe the results of lung transplantation of after cardiac death program, specifically the section regarding lung extraction donation. Twenty potential lung donors were obtained during the study. Most patients were male (19 cases), with a mean age of 42 years (36.5-49.5 years). A total of 33 lungs were donated (18 right and 15 left lungs). Most extractions were multiorganic (19 cases). One liver, 19 kidneys, 2 pancreas, and 19 corneas were obtained from these donors; bone tissue was obtained from all donors. The transplantation was bipulmonary in 13 cases and unipulmonary in 7. Thirty days after transplantation, 2 recipients died, 1 died of stroke associated with bilateral pneumonia and 1 died of hypovolemic shock resulting from hemothorax. The remaining 18 patients were progressing well at 30 days. Our data suggest that lung transplantation from patients after extrahospitalary cardiac death is feasible.

Brain Death, Paternalism, and the Language of “Death”

The controversy surrounding the dead donor rule and the adequacy of neurological criteria for death continues unabated. However, despite disagreement on fundamental theoretical questions, I argue that there is significant (but not complete) agreement on the permissibility of organ retrieval from heart-beating donors. Many disagreements are rooted in disputes surrounding language meaning and use, rather than the practices of transplant medicine. Thus I suggest that the debate can be fruitfully recast in terms of a dispute about language. Given this recasting, I argue that the language used to describe organ donation is misleading and paternalistic. Finally, I suggest that the near-agreement on the permissibility of heart-beating organ retrieval ought to be reconsidered. If the paternalism is not justified, then either the language used to describe organ transplantation must change radically, or it would seem to follow that much of the transplant enterprise lacks ethical justification.

Maximum tolerable warm ischaemia time in transplantation from non-heart-beating-donors

Donation after cardiac death is defined as organ donation once death is declared after irreversible cessation of circulatory and respiratory functions. The aim of this subjective review is to evaluate the outcome of grafts and recipients in consideration of the length of ischaemia and individuating those who can be considered suitable donors after cardiac arrest. Our main conclusion is that graft and patient survival are comparable either if the organs come from non-heart-beating-donors (NHBD) or heart beating donors (HBD) but complications were reported more frequently in NHBD than in HBD. Warm ischaemia time reduction and close selection of donors are keys to successful NHBD transplantation.

Pulmonary Function Assessment Method with Type II Non-heart Beating Donors in Spain is Valid

Lung transplantation unit from Hospital 12 de Octubre began its work in October 2008. In the last five years, 80 lung transplants have been performed with a hospital mortality rate of 6.5% and a five years survival of 79.7%. As a result of the need of obtaining a greater number of donors, and encouraged by the outpatient non heart beating donors program within our hospital, we considered the possibility of assessing these donors lung grafts. We have followed the methodology designed and set off with good results by other hospitals in the area of Madrid. Nevertheless some changes have been included such as Bithermical multiorgan preservation, where abdominal organs are preserved in normothermia and thoracic ones in hypothermia. However, this methodology has not been scientifically proven. We have reproduced in a laboratory lung function assessment manoeuvres of pulmonary grafts from non heart beating donors. Then we have compared the correlation with the lung function assessment before cardiac arrest, applying the procedure on 40 pigs. Outcomes are promising.

Movements after the clinical diagnosis of brain death: supraspinal motor responses or spinal reflexes

In a recent issue of Critical Care, Wu and Orizaola Balaguer [1] hypothesized that nociceptive head turning after brain death (BD) is a spinal reflex. We argue that it can be a supraspinal response, which would invalidate a diagnosis of BD. The sternocleidomastoid and trapezius are innervated by the spinal nucleus of the accessory nerve extending from the lower medulla to the ventral horn of the spinal cord (C1-C4) [2]. Lower motor neurons from the lower medulla to C2 project to the sternocleidomastoid [2], contributing to the reported motor responses. The spinal nerve roots of the accessory nerve ascend through the foramen magnum and descend through the jugular foramen. Compression of the vertebral-basilar arteries (causing intracranial circulatory arrest) and the spinal nerve roots by cerebellar tonsillar herniation at the foramen magnum would abolish the spinal accessory nerve reflex as well as cause cervicomedullary infarction. The pyramidal tract projecting from the telencephalon controls voluntary movements. Subcortical nuclei in the diencephalon, mesencephalon, and rhombencephalon control non-voluntary movements. Complex movements are generally explained as spinal reflexes rather than supraspinal motor responses, despite an incidence of 40% to 50% in heart-beating donors [3]. Dismissal of supraspinal motor responses is incongruent with the finding [4] that, on histopathological examination, about 60% of heart-beating donors have normal or minimal ischemic injury to the brainstem. If (as these histopathological findings show) the subcortical nuclei are possibly uninjured, then the supraspinal origin of movements cannot be excluded [5]. The absence of brainstem injury at autopsy raises doubt that all movements in BD are spinal motor reflexes. Additional histopathological data are needed to determine whether movements originate from supraspinal or spinal nuclei.

Postmortem and ex vivo carbon monoxide ventilation reduces injury in rat lungs transplanted from non–heart-beating donors

Postmortem and ex vivo carbon monoxide ventilation reduces injury in rat lungs transplanted from non–heart-beating donors