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Brain Death (brain + death)
Selected AbstractsETHICAL DEBATE OVER ORGAN DONATION IN THE CONTEXT OF BRAIN DEATHBIOETHICS, Issue 2 2010MARY JIANG BRESNAHAN ABSTRACT This study investigated what information about brain death was available from Google searches for five major religions. A substantial body of supporting research examining online behaviors shows that information seekers use Google as their preferred search engine and usually limit their search to entries on the first page. For each of the five religions in this study, Google listings reveal ethical controversy about organ donation in the context of brain death. These results suggest that family members who go online to find information about organ donation in the context of brain death would find information about ethical controversy in the first page of Google listings. Organ procurement agencies claim that all major world religions approve of organ donation and do not address the ethical controversy about organ donation in the context of brain death that is readily available online. [source] Brain Death Activates Donor Organs and Is Associated with a Worse I/R Injury After Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2007S. Weiss The majority of transplants are derived from donors who suffered from brain injury. There is evidence that brain death causes inflammatory changes in the donor. To define the impact of brain death, we evaluated the gene expression of cytokines in human brain dead and ideal living donors and compared these data to organ function following transplantation. Hepatic tissues from brain dead (n = 32) and living donors (n = 26) were collected at the time of donor laparotomy. Additional biopsies were performed before organ preservation, at the time of transplantation and one hour after reperfusion. Cytokines were assessed by real-time reverse transcriptase,polymerase chain reaction (RT,PCR) and cytometric bead array. Additionally, immunohistological analysis of tissue specimens was performed. Inflammatory cytokines including IL-6, IL-10, TNF-,, TGF-, and MIP-1, were significantly higher in brain dead donors immediately after laparotomy compared to living donors. Cellular infiltrates significantly increased in parallel to the soluble cytokines IL-6 and IL-10. Enhanced immune activation in brain dead donors was reflected by a deteriorated I/R injury proven by elevated alanin-amino-transferase (ALT), aspartat-amino-transferase (AST) and bilirubin levels, increased rates of acute rejection and primary nonfunction. Based on our clinical data, we demonstrate that brain death and the events that precede it are associated with a significant upregulation of inflammatory cytokines and lead to a worse ischemia/reperfusion injury after transplantation. [source] Early Hemodynamic Injury During Donor Brain Death Determines the Severity of Primary Graft Dysfunction after Lung TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2007V. S. Avlonitis Sympathetic discharge and hypertensive crisis often accompany brain death, causing neurogenic pulmonary edema. Progressive systemic inflammatory response develops, which can injure the lung further. We investigated whether (a) early hemodynamic injury during donor brain death increases reperfusion injury after lung transplantation and (b) delaying lung recovery would augment reperfusion injury further, because of the progressive systemic inflammatory response in the donor. Brain death was induced by intracranial balloon inflation in rats, with or without ,-adrenergic blockade pretreatment to prevent the hypertensive crisis. Another group of rats had a sham procedure. Lungs were retrieved 15 min after brain death or sham procedure and reperfused using recipient rats. In a fourth group, brain death was induced and the lungs were retrieved 5 h after brain death and reperfused. Postreperfusion, lungs retrieved early from untreated brain-dead donors developed more severe reperfusion injury, as assessed by functional parameters and inflammatory markers, than those from sham or alpha-blockade-treated donors. Lungs retrieved late from brain-dead donors had similar inflammatory markers after reperfusion to those retrieved early, but significantly lower pulmonary vascular resistance. Early hemodynamic damage during donor brain death increases reperfusion injury after lung transplantation. Delaying retrieval may allow the lung to recover from the hemodynamic injury. [source] Undulating toe movements in brain death,EUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2004G. Saposnik For many years, death implied immobility. Nevertheless, there are anecdotal reports of spontaneous or reflex movements (SRMs) in patients with Brain death (BD). The presence of some movements can preclude the diagnosis of BD, and consequently, the possibility of organ donation for transplantation. McNair and Meador [(1992), Mov Dord7: 345,347] described the presence of undulating toe flexion movements (UTF) in BD patients. UTF consists in a sequential brief plantar flexion of the toes. Our aim was to determine the frequency, characteristics and predisposing factors of UTF movements in a prospective multicenter cohort study of patients with BD. Patients with confirmed diagnosis of BD were assessed to evaluate the presence of UTF using a standardized protocol. All patients had a routine laboratory evaluation, CT scan of the head, and EEG. Demographic, clinical, hemodynamic and blood gas concentration factors were analyzed. amongst 107 BD patients who fulfilled the AAN requirements, 47 patients (44%) had abnormal movements. UTF was observed in 25 (23%) being the most common movement (53%). Early evaluation (OR 4.3, CI95% 1.5,11.9) was a predictor of UTF in a multivariate regression model. The somato-sensory evoked potential (SSEPs) as well as brainstem auditory evoked potentials (BAEPs) did not elicit a cortical response in studied patients with UTF. This spinal reflex is probably integrated in the L5 and S1 segments of the spinal cord. Abnormal movements are common in BD, being present in more than 40% of individuals. UTF was the most common spinal reflex. In our sample, early evaluation was a predictor of UTF. Health care professionals, especially those involved in organ procurement for transplantation, must be aware of this sign. The presence of this motor phenomenon does not preclude the diagnosis of BD. [source] Brain death and its implications for management of the potential organ donorACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2009J. F. BUGGE The systemic physiologic changes that occur during and after brain death affect all organs suitable for transplantation. Major changes occur in the cardiovascular, pulmonary, endocrine, and immunological systems, and, if untreated may soon result in cardiovascular collapse and somatic death. Understanding these complex physiologic changes is mandatory for developing effective strategies for donor resuscitation and management in such a way that the functional integrity of potentially transplantable organs is maintained. This review elucidates these physiological changes and their consequences, and based on these consequences the rationale behind current medical management of brain-dead organ donors is discussed. [source] Systemic inflammation in the brain-dead organ donorACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2009A. BARKLIN Brain death itself impairs organ function in the potential donor, thereby limiting the number of suitable organs for transplantation. In addition, graft survival of kidneys obtained from brain-dead (BD) donors is inferior to that of kidneys obtained from living donors. Experimental studies confirm an inferior graft survival for the heart, liver and lungs from BD compared with living donors. The mechanism underlying the deteriorating effect of brain death on the organs has not yet been fully established. We know that brain death triggers massive circulatory, hormonal and metabolic changes. Moreover, the past 10 years have produced evidence that brain death is associated with a systemic inflammatory response. However, it remains uncertain whether the inflammation is induced by brain death itself or by events before and after becoming BD. The purpose of this study is to discuss the risk factors associated with brain death in general and the inflammatory response in the organs in particular. Special attention will be paid to the heart, lung, liver and kidney and evidence will be presented from clinical and experimental studies. [source] Medical and legal considerations of brain deathACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2004T. T. Randell Brain death was first defined in 1968, and since then laws on determining death have been implemented in all countries with active organ transplantation programs. As a prerequisite, the aetiology of brain death has to be known, and all reversible causes of coma have to be excluded. The regulations for the diagnosis of brain death are most commonly given by the national medical associations, and they vary between countries. Thus, the guidelines given in the medical textbooks are not universally applicable. The diagnosis is based on clinical examination, but confirmatory tests, such as angiography or EEG, are allowed on most occasions. Brain death is followed by cardiovascular and hormonal changes, which have implications in the management of a potential organ donor. Spinal reflexes are preserved, and motor and haemodynamic responses are frequently observed in brain dead patients. [source] Brain death: an important paradigm shift in the 20th centuryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2003G. Settergren The description of death in medical or pathophysiological terms changed during the last century. The focus of attention shifted from the condition of the heart to the state of the brain. The current paper investigates the time period from 1866, when the effects of an increased intracranial pressure (ICP) were studied experimentally, to 1967, when the first heart transplantation was performed. Between 1894 and 1965 four neurosurgeons: Horsley in England, Cushing in USA, Wertheimer in France and Frykholm in Sweden made important contributions. Documented discussions, if ventilator treatment should be stopped in patients with a dead brain and a beating heart, began in 1959. However, already during the latter part of the 19th century it was shown that the heart could continue to beat if artificial ventilation was performed, when spontaneous respiration had ceased due to a high ICP. Furthermore, brain death was by chance implemented in clinical practice in heart surgery with cardiopulmonary bypass (CPB) some years before the expressions ,death of the nervous system' and ,brain death' were coined. [source] Signal Transduction Pathways Involved in Brain Death-Induced Renal InjuryAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009H. R. Bouma Kidneys derived from brain death organ donors show an inferior survival when compared to kidneys derived from living donors. Brain death is known to induce organ injury by evoking an inflammatory response in the donor. Neuronal injury triggers an inflammatory response in the brain, leading to endothelial dysfunction and the release of cytokines in the circulation. Serum levels of interleukin-6, -8, -10, and monocyte chemoattractant protein-1 (MCP-1) are increased after brain death. Binding with cytokine-receptors in kidneys stimulates activation of nuclear factor-kappa B (NF-,B), selectins, adhesion molecules and production of chemokines leading to cellular influx. Mitogen-activated protein kinases (MAP-kinases) mediate inflammatory responses and together with NF-,B they seem to play an important role in brain death induced renal injury. Altering the activation state of MAP-kinases could be a promising drug target for early intervention to reduce cerebral injury related donor kidney damage and improve outcome after transplantation. [source] Early Hemodynamic Injury During Donor Brain Death Determines the Severity of Primary Graft Dysfunction after Lung TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2007V. S. Avlonitis Sympathetic discharge and hypertensive crisis often accompany brain death, causing neurogenic pulmonary edema. Progressive systemic inflammatory response develops, which can injure the lung further. We investigated whether (a) early hemodynamic injury during donor brain death increases reperfusion injury after lung transplantation and (b) delaying lung recovery would augment reperfusion injury further, because of the progressive systemic inflammatory response in the donor. Brain death was induced by intracranial balloon inflation in rats, with or without ,-adrenergic blockade pretreatment to prevent the hypertensive crisis. Another group of rats had a sham procedure. Lungs were retrieved 15 min after brain death or sham procedure and reperfused using recipient rats. In a fourth group, brain death was induced and the lungs were retrieved 5 h after brain death and reperfused. Postreperfusion, lungs retrieved early from untreated brain-dead donors developed more severe reperfusion injury, as assessed by functional parameters and inflammatory markers, than those from sham or alpha-blockade-treated donors. Lungs retrieved late from brain-dead donors had similar inflammatory markers after reperfusion to those retrieved early, but significantly lower pulmonary vascular resistance. Early hemodynamic damage during donor brain death increases reperfusion injury after lung transplantation. Delaying retrieval may allow the lung to recover from the hemodynamic injury. [source] ARE RECENT DEFENCES OF THE BRAIN DEATH CONCEPT ADEQUATE?BIOETHICS, Issue 2 2010ARI JOFFE ABSTRACT Brain death is accepted in most countries as death. The rationales to explain why brain death is death are surprisingly problematic. The standard rationale that in brain death there has been loss of integrative unity of the organism has been shown to be false, and a better rationale has not been clearly articulated. Recent expert defences of the brain death concept are examined in this paper, and are suggested to be inadequate. I argue that, ironically, these defences demonstrate the lack of a defensible rationale for why brain death should be accepted as death itself. If brain death is death, a conceptual rationale for brain death being equivalent to death should be clarified, and this should be done urgently. [source] Undulating toe movements in brain death,EUROPEAN JOURNAL OF NEUROLOGY, Issue 11 2004G. Saposnik For many years, death implied immobility. Nevertheless, there are anecdotal reports of spontaneous or reflex movements (SRMs) in patients with Brain death (BD). The presence of some movements can preclude the diagnosis of BD, and consequently, the possibility of organ donation for transplantation. McNair and Meador [(1992), Mov Dord7: 345,347] described the presence of undulating toe flexion movements (UTF) in BD patients. UTF consists in a sequential brief plantar flexion of the toes. Our aim was to determine the frequency, characteristics and predisposing factors of UTF movements in a prospective multicenter cohort study of patients with BD. Patients with confirmed diagnosis of BD were assessed to evaluate the presence of UTF using a standardized protocol. All patients had a routine laboratory evaluation, CT scan of the head, and EEG. Demographic, clinical, hemodynamic and blood gas concentration factors were analyzed. amongst 107 BD patients who fulfilled the AAN requirements, 47 patients (44%) had abnormal movements. UTF was observed in 25 (23%) being the most common movement (53%). Early evaluation (OR 4.3, CI95% 1.5,11.9) was a predictor of UTF in a multivariate regression model. The somato-sensory evoked potential (SSEPs) as well as brainstem auditory evoked potentials (BAEPs) did not elicit a cortical response in studied patients with UTF. This spinal reflex is probably integrated in the L5 and S1 segments of the spinal cord. Abnormal movements are common in BD, being present in more than 40% of individuals. UTF was the most common spinal reflex. In our sample, early evaluation was a predictor of UTF. Health care professionals, especially those involved in organ procurement for transplantation, must be aware of this sign. The presence of this motor phenomenon does not preclude the diagnosis of BD. [source] Movements in brain deathEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2001G. Saposnik [source] Phenomenological diversity of spinal reflexes in brain deathEUROPEAN JOURNAL OF NEUROLOGY, Issue 3 2000J. F. Spittler In brain death, spinal reflexes and automatisms are observed which may cause irritation and even doubt in the diagnosis. In the literature there are no dedicated descriptions of the diversity and of neuroanatomical considerations. In 278 examinations of 235 patients for the determination of brain death, on 42 occasions obvious spinal reflexes and/or spinal automatisms were observed in 27 brain dead bodies. Because they were not systematically searched for, minute forms have probably been missed. The reflexes (R) and automatisms (A) are described according to the time of observation in relation to the development of brain death, the presumable spinal localization and the possible phylogenetical interpretation. Especially disquieting examples are discussed in more detail, e.g. monophasic EndotrachealSuction,ThoracicContraction-R supposedly switched in segments C2,6 or TrapeziusPinch,ShoulderProtrusion-R conveyed by the accessory nerve (terminology according to the scheme: for the reflexes, Trigger-Response-R: for the automatisms, Movement-A). After these experiences a more thorough examination showed frequent observations of rather minute forms of spinal reflexes, as well as automatisms and even the Lazarus sign (in possibly more than two thirds of the examinations). An estimation of the factual frequency would necessitate special attention to those much more frequent but less obvious minute spinal reflexes and automatisms. [source] Attitudes of intensive care nurses towards brain death and organ transplantation: instrument development and testingJOURNAL OF ADVANCED NURSING, Issue 5 2006Jung Ran Kim BN MClinN DipN RN Aims., This paper reports the development and testing of an instrument assessing attitudes of Korean intensive care unit nurses. Background., Reluctance by healthcare professionals to identify brain-dead patients as a potential donor is one reason for a shortfall in transplantable organs in all countries. Organ donation from brain-dead patients is a particularly contentious issue in Korea, following recent legal recognition of brain death within the cultural context of Confucian beliefs. Method., A 38-item instrument was developed from the literature and key informant interviews, and validated by an expert panel and a pilot study. A survey was conducted with Korean intensive care unit nurses (n = 520) from October 2003 to January 2004. Principal component analysis with varimax rotation was used to determine construct validity. Item-to-total correlations and Cronbach's coefficient alpha were used to determine the scale's internal consistency and unidimensionality. Results., The scale demonstrated high internal consistency (alpha = 0·88). Principal component analysis yielded a four-component structure: Discomfort, Enhancing quality of life, Willingness to be a donor and Rewarding experience. Overall, Korean intensive care unit nurses showed positive attitudes towards organ transplantation, despite some mixed feelings. Conclusion., The attitude scale was reliable and valid for this cohort. Areas were identified where professional development may enhance positive attitudes towards organ transplantation from brain-dead donors. Effective education for intensive care unit nurses is necessary to increase the organ donor pool in Korea. Further research could test the instrument with other populations. [source] Brain death and its implications for management of the potential organ donorACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 10 2009J. F. BUGGE The systemic physiologic changes that occur during and after brain death affect all organs suitable for transplantation. Major changes occur in the cardiovascular, pulmonary, endocrine, and immunological systems, and, if untreated may soon result in cardiovascular collapse and somatic death. Understanding these complex physiologic changes is mandatory for developing effective strategies for donor resuscitation and management in such a way that the functional integrity of potentially transplantable organs is maintained. This review elucidates these physiological changes and their consequences, and based on these consequences the rationale behind current medical management of brain-dead organ donors is discussed. [source] Systemic inflammation in the brain-dead organ donorACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 4 2009A. BARKLIN Brain death itself impairs organ function in the potential donor, thereby limiting the number of suitable organs for transplantation. In addition, graft survival of kidneys obtained from brain-dead (BD) donors is inferior to that of kidneys obtained from living donors. Experimental studies confirm an inferior graft survival for the heart, liver and lungs from BD compared with living donors. The mechanism underlying the deteriorating effect of brain death on the organs has not yet been fully established. We know that brain death triggers massive circulatory, hormonal and metabolic changes. Moreover, the past 10 years have produced evidence that brain death is associated with a systemic inflammatory response. However, it remains uncertain whether the inflammation is induced by brain death itself or by events before and after becoming BD. The purpose of this study is to discuss the risk factors associated with brain death in general and the inflammatory response in the organs in particular. Special attention will be paid to the heart, lung, liver and kidney and evidence will be presented from clinical and experimental studies. [source] Insulin alters cytokine content in two pivotal organs after brain death: a porcine modelACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 5 2008A. BARKLIN Background: To optimize the quantity and quality of organs available for transplantation, it is crucial to gain further insight into the treatment of brain dead organ donors. In the current study we hypothesized that insulin treatment after brain death alters cytokine content in the heart, liver, and kidney. Methods: Sixteen brain dead pigs (35,40 kg) were treated with either (1) no insulin [brain dead without insulin treatment treatment (BD)], or (2) insulin infusion intravenously (i.v.) at a constant rate of 0.6 mU/kg/min during 360 min [brain dead with insulin treatment (BD+I)]. Blood glucose was clamped at 4.5 mmol/l by infusion of 20% glucose. Blood samples for insulin, glucose, catecholamines, free fatty acids, and glucagon were obtained during the experimental period. Six hours after brain death biopsies were taken from the heart, liver, and kidney. These were analyzed for cytokine mRNA and proteins [tumor necrosis factor-, (TNF-,), interleukin (IL)-6, and IL-10]. Results: The BD+I compared with the BD animals had lower IL-6 concentrations in the right ventricle of the heart (P=0.001), in the renal cortex (P=0.04) and in the renal medulla (P=0.05), and lower IL-6 mRNA in the renal medulla (P=0.0002). Furthermore, the BD+I animals had lower concentrations in the renal medulla of IL-10 (P=0.01), and tended to have lower TNF-, in the renal cortex (P=0.06) than the BD animals. In the right ventricle of the heart TNF-, mRNA and IL-10 mRNA were higher in the BD+I than in the BD group (P=0.002 and 0.004). Conclusion: Insulin has anti-inflammatory effects on cytokine concentration in the heart and kidney after brain death. [source] Medical and legal considerations of brain deathACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2004T. T. Randell Brain death was first defined in 1968, and since then laws on determining death have been implemented in all countries with active organ transplantation programs. As a prerequisite, the aetiology of brain death has to be known, and all reversible causes of coma have to be excluded. The regulations for the diagnosis of brain death are most commonly given by the national medical associations, and they vary between countries. Thus, the guidelines given in the medical textbooks are not universally applicable. The diagnosis is based on clinical examination, but confirmatory tests, such as angiography or EEG, are allowed on most occasions. Brain death is followed by cardiovascular and hormonal changes, which have implications in the management of a potential organ donor. Spinal reflexes are preserved, and motor and haemodynamic responses are frequently observed in brain dead patients. [source] Brain death: an important paradigm shift in the 20th centuryACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 9 2003G. Settergren The description of death in medical or pathophysiological terms changed during the last century. The focus of attention shifted from the condition of the heart to the state of the brain. The current paper investigates the time period from 1866, when the effects of an increased intracranial pressure (ICP) were studied experimentally, to 1967, when the first heart transplantation was performed. Between 1894 and 1965 four neurosurgeons: Horsley in England, Cushing in USA, Wertheimer in France and Frykholm in Sweden made important contributions. Documented discussions, if ventilator treatment should be stopped in patients with a dead brain and a beating heart, began in 1959. However, already during the latter part of the 19th century it was shown that the heart could continue to beat if artificial ventilation was performed, when spontaneous respiration had ceased due to a high ICP. Furthermore, brain death was by chance implemented in clinical practice in heart surgery with cardiopulmonary bypass (CPB) some years before the expressions ,death of the nervous system' and ,brain death' were coined. [source] Pediatric cardiothoracic domino transplantation: The psychological costs and benefitsPEDIATRIC TRANSPLANTATION, Issue 5 2004Jo Wray Abstract:, The first domino transplants were carried out in the UK in 1987, since which time 52 such procedures have been carried out involving patients within the paediatric cardiothoracic transplant programmes of Harefield and Great Ormond Street Hospitals. Although there are medical advantages in using domino organs , such as the ability for preoperative cross-matching, the heart not being subjected to the biochemical changes of brain death and less post-transplant coronary artery disease in the recipients of domino hearts compared with the recipients of hearts from cadaveric donors , the psychological sequelae for both donor and recipient have not been previously studied. The objective of this study was to identify the main psychological themes for patients involved in the domino programmes at the two hospitals, focusing on those situations where both patients were cared for in the same tertiary centre. Patients and their families were interviewed during routine outpatient clinic visits. Negative themes identified by patients included anxiety, guilt, resentment and anger if either patient had a poor outcome or suffered significant complications, disappointment and low self-esteem for potential donors whose heart was not used and recipient awareness of donor characteristics. Positive themes included gratefulness, comfort for the recipient that someone had not had to die for them directly and the benefit to the donor of giving their heart to another patient. In conclusion, domino transplantation has many medical advantages but there are significant negative psychological concomitants which need to be addressed within the multi-disciplinary management of these patients. [source] The Sleeping Giant Awakens,Liver Transplantation in ChinaAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2010J. Fung The number of liver transplants in China continues to rise, but the challenge of increasing the use of donation after brain death remains daunting. See Article by Allam et al on page 1834. [source] Successful Organ Transplantation from Donors Poisoned with a Carbamate InsecticideAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010J. H. Garcia Currently, liver transplantation is the only option for patients with end-stage liver disease. In Brazil, the mortality rate on the waiting list is about 25%. Multiple strategies to expand the donor pool are being pursed, however, grafts from poisoned donors are rarely used. This report documents successful liver, kidney and heart transplantations from four female donors who suffered brain death by hypoxia despite cardiopulmonary resuscitation following Aldicarb exposure ([2-methyl-2-(methylthio)propionaldehyde O-(methylcarbamoyl)-oxime]). The success rate of 12 grafts from four donors poisoned by Aldicarb was 91% 6 months after transplantation. Poisoned patients are another pool of organ donors who at present are probably underused by transplantation services. More studies are necessary to confirm the safety for the recipients. [source] Donor Intervention and Organ Preservation: Where Is the Science and What Are the Obstacles?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010S. Feng The organ shortage is widely acknowledged as the most critical factor hindering the full realization of success for solid organ transplantation. Innovation in the areas of donor management and organ preservation offers the most realistic hope to improve both the quality and size of the current organ supply. Although the basic science dissecting the complex processes of brain death and ischemia/reperfusion injury is replete with exciting discoveries, the clinical science investigating donor management and organ preservation is sparse in contrast. This review will survey the current landscape of trials to mitigate organ injury through interventions administered to donors in vivo or organs ex vivo. Consideration will then be given to the scientific, logistical and ethical obstacles that impede the transformation of laboratory breakthroughs into innovative treatments that simultaneously improve organ quality and supply. [source] Modulation of Brain Dead Induced Inflammation by Vagus Nerve StimulationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010S. Hoeger Because the vagus nerve is implicated in control of inflammation, we investigated if brain death (BD) causes impairment of the parasympathetic nervous system, thereby contributing to inflammation. BD was induced in rats. Anaesthetised ventilated rats (NBD) served as control. Heart rate variability (HRV) was assessed by ECG. The vagus nerve was electrically stimulated (BD + STIM) during BD. Intestine, kidney, heart and liver were recovered after 6 hours. Affymetrix chip-analysis was performed on intestinal RNA. Quantitative PCR was performed on all organs. Serum was collected to assess TNF, concentrations. Renal transplantations were performed to address the influence of vagus nerve stimulation on graft outcome. HRV was significantly lower in BD animals. Vagus nerve stimulation inhibited the increase in serum TNF, concentrations and resulted in down-regulation of a multiplicity of pro-inflammatory genes in intestinal tissue. In renal tissue vagal stimulation significantly decreased the expression of E-selectin, IL1, and ITGA6. Renal function was significantly better in recipients that received a graft from a BD + STIM donor. Our study demonstrates impairment of the parasympathetic nervous system during BD and inhibition of serum TNF, through vagal stimulation. Vagus nerve stimulation variably affected gene expression in donor organs and improved renal function in recipients. [source] Liver Transplantation with Grafts from Controlled Donors after Cardiac Death: A 20-Year Follow-up at a Single CenterAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010S. Yamamoto The first liver transplantation (LTx) in Sweden was performed in 1984, but brain death as a legal death criterion was not accepted until 1988. Between November 1984 and May 1988, we performed 40 consecutive LTxs in 32 patients. Twenty-four grafts were from donors after cardiac death (DCD) and 16 grafts from heart-beating donors (HBD). Significantly, more hepatic artery thrombosis and biliary complications occurred in the DCD group (p < 0.01 and p < 0.05, respectively). Graft and patient survival did not differ between the groups. In the total group, there was a significant difference in graft survival between first-time LTx grafts and grafts used for retransplantation. There was better graft survival in nonmalignant than malignant patients, although this did not reach statistical significance. Multivariate analysis revealed cold ischemia time and post-LTx peak ALT to be independent predictive factors for graft survival in the DCD group. In the 11 livers surviving 20 years or more, follow-up biopsies were performed 18,20 years post-LTx (n = 10) and 6 years post-LTx (n = 1). Signs of chronic rejection were seen in three cases, with no difference between DCD and HBD. Our analysis with a 20-year follow-up suggests that controlled DCD liver grafts might be a feasible option to increase the donor pool. [source] Attitudes of the American Public toward Organ Donation after Uncontrolled (Sudden) Cardiac DeathAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010M. L. Volk Concerns about public support for organ donation after cardiac death have hindered expansion of this practice, particularly rapid organ recovery in the context of uncontrolled (sudden) cardiac death (uDCD). A nationally representative Internet-based panel was provided scenarios describing donation in the context of brain death, controlled cardiac death and uncontrolled cardiac death. Participants were randomized to receive questions about trust in the medical system before or after the rapid organ recovery scenario. Among 1631 panelists, 1049 (64%) completed the survey. Participants expressed slightly more willingness to donate in the context of controlled and uncontrolled cardiac death than after brain death (70% and 69% vs. 66%, respectively, p < 0.01). Eighty percent of subjects (95% CI 77,84%) would support having a rapid organ recovery program in their community, though 83% would require family consent or a signed donor card prior to invasive procedures for organ preservation. The idea of uDCD slightly decreased trust in the medical system from 59% expressing trust to 51% (p = 0.02), but did not increase belief that a signed donor card would interfere with medical care (28% vs. 32%, p = 0.37). These findings provide support for the careful expansion of uDCD, albeit with formal consent prior to organ preservation. [source] ASTS Recommended Practice Guidelines for Controlled Donation after Cardiac Death Organ Procurement and TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009D. J. Reich The American Society of Transplant Surgeons (ASTS) champions efforts to increase organ donation. Controlled donation after cardiac death (DCD) offers the family and the patient with a hopeless prognosis the option to donate when brain death criteria will not be met. Although DCD is increasing, this endeavor is still in the midst of development. DCD protocols, recovery techniques and organ acceptance criteria vary among organ procurement organizations and transplant centers. Growing enthusiasm for DCD has been tempered by the decreased yield of transplantable organs and less favorable posttransplant outcomes compared with donation after brain death. Logistics and ethics relevant to DCD engender discussion and debate among lay and medical communities. Regulatory oversight of the mandate to increase DCD and a recent lawsuit involving professional behavior during an attempted DCD have fueled scrutiny of this activity. Within this setting, the ASTS Council sought best-practice guidelines for controlled DCD organ donation and transplantation. The proposed guidelines are evidence based when possible. They cover many aspects of DCD kidney, liver and pancreas transplantation, including donor characteristics, consent, withdrawal of ventilatory support, operative technique, ischemia times, machine perfusion, recipient considerations and biliary issues. DCD organ transplantation involves unique challenges that these recommendations seek to address. [source] Combining Cariporide with Glyceryl Trinitrate Optimizes Cardiac Preservation During Porcine Heart TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009A. J. Hing Sodium,hydrogen exchange inhibitors, such as cariporide, are potent cardioprotective agents, however, safety concerns have been raised about intravenously (i.v.) administered cariporide in humans. The aim of this study was to develop a preservation strategy that maintained cariporide's cardioprotective efficacy during heart transplantation while minimizing recipient exposure. We utilized a porcine model of orthotopic heart transplantation that incorporated donor brain death and 14 h static heart storage. Five groups were studied: control (CON), hearts stored in Celsior; CAR1, hearts stored in Celsior with donors and recipients receiving cariporide (2 mg/kg i.v.) prior to explantation and reperfusion, respectively; CAR2, hearts stored in Celsior supplemented with cariporide (10 ,mol/L); GTN, hearts stored in Celsior supplemented with glyceryl trinitrate (GTN) (100 mg/L); and COMB, hearts stored in Celsior supplemented with cariporide (10 ,mol/L) plus GTN (100 mg/L). A total of 5/5 CAR1 and 5/6 COMB recipients were weaned from cardiopulmonary bypass compared with 1/5 CON, 1/5 CAR2 and 0/5 GTN animals (p = 0.001). Hearts from the CAR1 and COMB groups demonstrated similar cardiac function and troponin release after transplantation. Supplementation of Celsior with cariporide plus GTN provided superior donor heart preservation to supplementation with either agent alone and equivalent preservation to that observed with systemic administration of cariporide to the donor and recipient. [source] Kidney Injury Molecule-1 is an Early Noninvasive Indicator for Donor Brain Death-Induced Injury Prior to Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009W. N. Nijboer With more marginal deceased donors affecting graft viability, there is a need for specific parameters to assess kidney graft quality at the time of organ procurement in the deceased donor. Recently, kidney injury molecule-1 (Kim-1) was described as an early biomarker of renal proximal tubular damage. We assessed Kim-1 in a small animal brain death model as an early and noninvasive marker for donor-derived injury related to brain death and its sequelae, with subsequent confirmation in human donors. In rat kidney, real-time PCR revealed a 46-fold Kim-1 gene upregulation after 4 h of brain death. In situ hybridization showed proximal tubular Kim-1 localization, which was confirmed by immunohistochemistry. Also, Luminex assay showed a 6.6-fold Kim-1 rise in urine after 4 h of brain death. In human donors, 2.5-fold kidney injury molecule-1 (KIM-1) gene upregulation and 2-fold higher urine levels were found in donation after brain death (DBD) donors compared to living kidney donors. Multiple regression analysis showed that urinary KIM-1 at brain death diagnosis was a positive predictor of recipient serum creatinine, 14 days (p < 0.001) and 1 year (p < 0.05) after kidney transplantation. In conclusion, we think that Kim-1 is a promising novel marker for the early, organ specific and noninvasive detection of brain death-induced donor kidney damage. [source] | ||||||||||||||||||||||