Brain-dead Multi-organ Donors Research Articles

Human blood vessel microbiota in healthy adults based on common femoral arteries of brain-dead multi-organ donors.

Discovery of human microbiota is fundamentally changing our perceptions of certain diseases and their treatments. However little is known about the human blood vessel microbiota, it may have important effects on vascular pathological lesions and vascular homograft failure. In our prospective survey study fourteen femoral arteries, harvested from donors in multi-organ donations, were examined using the V3-V4 region 16S rRNA sequencing method. The most abundant phyla in the human vascular microbiota were Proteobacteria, Firmicutes and Actinobacteria. At the genus level, the most abundant taxa were Staphylococcus, Corynebacterium, Pseudomonas, Bacillus, Acinetobacter and Propionibacterium. Of the bacterial taxa that have an indirect effect on the development of atherosclerosis, we found Porphyromonas gingivalis, Prevotella nigrescens and Enterobacteriaceae spp. with different abundances in our samples. Of the bacteria that are more common in the intestinal flora of healthy than of atherosclerosis patients, Roseburia and Ruminococcus occurred in the majority of samples. The human arterial wall has a unique microbiota that is significantly different in composition from that of other areas of the body. Our present study provides a basis for ensuing research that investigates the direct role of the microbiota in vascular wall abnormalities and the success of vascular allograft transplantations.

Donor Simvastatin Treatment is More Effective in Donors with Low Plasma Levels of Arginine

<h3>Purpose</h3> Brain death may lead to a severe impairment of endothelial function and affect graft function. Recent study shows that simvastatin treatment to the organ donor decreases plasma biomarker levels of myocardial injury and heart failure and reduces the number of acute rejection episodes with hemodynamic compromise early after heart transplantation. However, the mechanisms of donor simvastatin treatment remain unknown. Therefore, we analyzed the plasma metabolomics of brain-dead heart transplant donors with or without simvastatin treatment to examine the molecular background of the beneficial effects. <h3>Methods</h3> In a prospective, double-blinded randomized controlled trial, 84 multiorgan donors were randomly assigned to receive either 80 mg of simvastatin (n=42) via nasogastric tube or to receive no simvastatin (n=42). Plasma samples from 84 human brain-dead multi-organ donors were collected immediately before organ procurement. We profiled over 100 targeted metabolites using mass spectrometry. <h3>Results</h3> We found that arginine and tryptophan were weakly negatively correlated with simvastatin treatment. Univariate Cox regression analysis showed that low levels of arginine were significantly associated with acute rejection and graft-related mortality (Figure 1 A,B). Additionally, we saw that donor simvastatin treatment significantly reduced the number of acute rejections by 41% (p=0.012) in low arginine group within the first year (Figure 1C). There was no difference in donor demographics between the groups. However, there was a statistically significantly higher need for mechanical circulatory support for hearts from donors with low arginine levels. <h3>Conclusion</h3> This study shows that donor simvastatin treatment could be more efficient in brain-dead heart transplant donors with low arginine. Further analysis will be conducted by exploring the interplay between arginine and simvastatin in detail. The complete results will be presented at the ISHLT2022 congress.

Plasma proteome of brain-dead organ donors predicts heart transplant outcome

The pathophysiological changes related to brain death may affect the quality of the transplanted organs and expose the recipients to risks. We probed systemic changes reflected in donor plasma proteome and investigated their relationship to heart transplant outcomes. Plasma samples from brain-dead multi-organ donors were analyzed by label-free protein quantification using high-definition mass spectrometry. Unsupervised and supervised statistical models were used to determine proteome differences between brain-dead donors and healthy controls. Proteome variation and the corresponding biological pathways were analyzed and correlated with transplant outcomes. Statistical models revealed that donors had a unique but heterogeneous plasma proteome with 237 of 463 proteins being changed compared to controls. Pathway analysis showed that coagulation, gluconeogenesis, and glycolysis pathways were upregulated in donors, while complement, LXR/RXR activation, and production of nitric oxide and reactive oxygen species in macrophages pathways were downregulated. In point-biserial correlation analysis, lysine-specific demethylase 3A was moderately correlated with any grade and severe PGD. In univariate and multivariate Cox regression analyses myosin Va and proteasome activator complex subunit 2 were significantly associated with the development of acute rejections with hemodynamic compromise within 30 days. Finally, we found that elevated levels of lysine-specific demethylase 3A and moesin were identified as predictors for graft-related 1-year mortality in univariate analysis. We show that brain death significantly changed plasma proteome signature Donor plasma protein changes related to endothelial cell and cardiomyocyte function, inflammation, and vascular growth and arteriogenesis could predict transplant outcome suggesting a role in donor evaluation.

BRAIN DEATH ALTERS ECTONUCLEOTIDASE ACTIVITIES AND PURINE NUCLEOTIDE LEVELS IN HUMAN PLASMA

Background: Profound metabolic and molecular changes triggered by brain death may significantly affect graft dysfunction in the recipient. However, the effects of brain death on transplanted organs are largely unknown and no clinical biomarker is available to assess and treat organ grafts to improving transplantation outcomes. The purpose of this study is to investigate the plasma metabolic alterations profile of human brain-dead organ donors. Methods: We analyzed plasma samples from 119 human brain-dead multi-organ donors taken immediately before organ procurement and samples from 48 healthy volunteers. We profiled over 100 metabolites using targeted ultra-performance liquid chromatography-tandem mass spectrometry. We determined biological pathways that are enriched in the significant metabolites. Results: Based on multivariate analysis of metabolite data, 29 metabolites were found to be expressed at significantly different levels between brain-dead donors and healthy controls plasma group. Interestingly, brain death induced rapid up-regulation of nucleotide catabolizing soluble ectonucleotidases, which leads to the observed shift in plasma nucleotide levels. Pathway enrichment analysis suggested that these metabolites were involved in purine metabolism, methylhistidine metabolism, glycine metabolism, and phosphatidylethanolamine biosynthesis. Significant metabolites associated with disease terms such as early markers of myocardial injury, chronic renal failure and cardiogenic shock, among others. Conclusion: The metabolic profile of brain-dead organ donors described in this study sheds light on the molecular level effects of brain injury on systemic level. Altered metabolites such as purine nucleosides may be the members of a communication network between the brain and the vascular system in physiological and pathological conditions.

Plasma Metabolomic Profile of Human Brain-Dead Organ Donors

Profound metabolic and molecular changes triggered by solid organ donor brain death may significantly affect posttransplant graft function. However, the effects of brain death on transplanted organs are poorly understood and no clinical biomarker or targeted therapy is available to predict or prevent primary or late graft dysfunction, respectively. This study elaborates the plasma metabolomic profile of human brain-dead organ donors. We compared plasma samples from 119 human brain-dead multi-organ donors, taken immediately before organ procurement, to samples from 48 healthy volunteers. We employed targeted ultra-performance liquid chromatography-tandem mass spectrometry to profile over 100 metabolites. The metabolite profiles of the brain-dead donors and healthy individuals overlapped, but both groups also exhibited unique metabolites. Based on unsupervised and supervised multivariate analysis of metabolite profiles, 29 metabolites were found to be expressed at significantly different levels between brain-dead donors and controls. Pathway enrichment analysis suggested that these metabolites were involved in purine metabolism, methylhistidine metabolism, glycine metabolism, and phosphatidylethanolamine biosynthesis. Interestingly, brain death induced the rapid up-regulation of purine nucleosides as well as an increase in serine levels in plasma. The metabolomic profile of brain-dead organ donors described in this study sheds light on the molecular level effects of brain injury on a systemic level. Whether the metabolites presented here represent the systemic inflammatory reaction or predict later allograft function, remains to be fully elucidated. The complete analysis will be presented at the ISHLT 2020 congress.

Differential sensitivity of human islets from obese versus lean donors to chronic high glucose or palmitate.

Due to the shortage of multi-organ donors, human pancreatic islet transplantation has now been extended to islets originating from obese subjects. In this study, our aim is to compare the respective sensitivity of human islets from lean vs obese donors to chronic high glucose or high palmitate. Human islets were isolated from pancreases harvested from brain-dead multi-organ donors. Islets were cultured during 72 hours in the presence of moderate (16.7 mmol/L) or high (28 mmoL/L) glucose concentrations, or glucose (5.6 mmoL/L) and palmitate (0.4 mmoL/L), before measurement of their response to glucose. We first observed a greater insulin response in islets from obese donors under both basal and high-glucose conditions, confirming their hyperresponsiveness to glucose. When islets from obese donors were cultured in the presence of moderate or high glucose concentrations, insulin response to glucose remained unchanged or was slightly reduced, as opposed to that observed in lean subjects. Moreover, culturing islets from obese donors with high palmitate also induced less reduction in insulin response to glucose than in lean subjects. This partial protection of obese islets is associated with less induction of inducible nitric oxide synthase in islets, together with a greater expression of the transcription factor forkhead box O1 (FOXO1). Our data suggest that in addition to an increased sensitivity to glucose, islets from obese subjects can be considered as more resistant to glucose and fatty acid excursions and are thus valuable candidates for transplantation.

P2.29: IGL-1 solution for the preservation of human intestine: the first report in the literature

Introduction: IGL-1 is a newer preservation solution largely resembling University Wisconsin (UW) solution in terms of ingredients but where the viscous starch has been replaced by polyethylene glycol resulting in lower viscosity. In addition, IGL-1 has low potassium and high sodium concentrations (extracellular-type solution). The solution has been used in several European countries for the preservation of kidneys, pancreases and livers with efficacy and safety comparable to those of UW or Custodiol. However, a systematic appraisal of the intestinal preservation injury using ILG-1 is missing. Methods: Following aortic retrograde perfusion with 4 liters IGL-1, the ileum of fifteen deceased, brain dead multiorgan donors was retrieved and stored at 4C. Samples were obtained after 8h, 14h and 24 hours of cold storage. Histology (Chiu/Park scale), Goblet cells (GC) count, apoptosis (active caspase 3) and tight junction proteins claudin 3 and Zonula occludens (ZO)-1 were studied. Results: Eight hours of cold storage resulted in a moderate epithelial detachment form lamina propria (median Chiu grade 2 (range 1–3) and minimal GC depletion. Preservation injury progressed to a median grade of 3 (range 2–5) after 14 hours and remained at similar levels at 24 hours. Active Caspase-3 was very low or absent at all time-points. After 8h ZO-1 expression was well preserved along the entire villus but became discontinuous after 14 hours of cold storage. Claudin 3 staining pattern remained well preserved throughout the entire cold storage. Conclusions: The development of the preservation injury in the human intestine following perfusion and storage in IGL-1 appears similar with the other solutions. Interestingly, the structural preservation injury did not seem to continue to worsen after 14 hours while the injury at subcellular level advanced further.

Surgical technique and outcomes of uteri retrieval from brain-dead multi-organ donors: a preclinical research of human uterine transplantation

Objective: To evaluate the surgical technique and outcomes of uteri retrieval from brain-dead multi-organ donors.This study is a preclinical research of human living uterine transplantation. Methods: From May, 2015 to May, 2017, four uteri retrieval procedures, characterized with radical hysterectomy and uterine vascular pedicles dissection, were performed in multi-organ brain-dead donors.The uterus was the third authorized organ after the kidney and liver retrieval procedures in the first two cases.The uterine pedicles included the uterus, ovaries, fallopian tubes, the upper one-third of the vagina and internal iliac vessels or external iliac vessels.The perfusion of the uterus was conducted after the retrieval for evaluating the availability, followed by histopathological examination of the uterine issues per 30 minutes. Results: Since the uterine vein was quite difficult to identify and dissect in the first two case, which result in the rupture of triple uterine veins.Therefore, the uterine venous vessels including uterine vein connected with internal iliac vein and internal iliac arteries were selected as vascular grafts and dissected successfully in the last two cases, which could be perfused with the mixture of 4 ℃ heparinized physiological saline through each artery because of shortening the surgical time and arranging the uterine procurement as the first authorized organ procedure.Mean (SD) operative time was 152.5±39.0 min (115-215 min, n=4). Conclusion: Our preliminary experience indicated that the uterus could be retrieved from the brain-dead multi-organ donors and transplanted to the recipient.The attempt of skeletonizing the uterine veins should be replaced by dissection of internal iliac vein.

Factors influencing the contamination rates of the conjunctival swabs and organ culture media of human donor eyes

This study assessed the influence of donor, environmental, and logistical factors on the contamination rates of the conjunctival swabs and organ culture media of human donor eyes.In total, 1008 conjunctival swabs and 418 organ culture media samples from 504 consecutive human donor eyes were analyzed. Cross-tabulation, chi-squared tests, and Fisher's exact tests were used to assess the influence of the different factors on the contamination rates of the conjunctival swabs and organ culture media.The overall contamination rates were 28.4% for the conjunctival swabs and 1.0% for the organ culture media. A prolonged time between death and the conjunctival swab collection was associated with an increased conjunctival swab contamination rate [odds ratio (OR) = 1.9, 95% confidence interval (CI) = 1.2–3.0, P = .007]. The highest conjunctival swab contamination rate was found in the corneas procured in external institutions (outside the university hospital) (44.1%, OR = 3.6, 95%CI = 1.5–8.4, P = .003). Hospitalization times of 2 to 7 days prior to death were associated with an increased conjunctival swab contamination risk (OR = 2.6, 95%CI = 1.1–5.8, P = .021). However, the sex, age, cause of donor death, differentiation between septic and aseptic donors, differentiation between heart-beating brain-dead multiorgan donors and cadaveric donors, a warmer mean monthly temperature, and death to corneoscleral disc excision time did not significantly increase the conjunctival swab contamination risk. In addition, none of these factors affected the organ culture media contamination risk. Moreover, a positive conjunctival swab did not significantly increase the media contamination risk (P = .08). Surprisingly, the microorganisms causing media contamination were present at 50% of the amount detected on the conjunctival surface of the respective donor eye.A prolonged time between death and the conjunctival swab collection, a hospitalization time of 2 to 7 days prior to death, and corneal collection outside the university hospital seemed to be the main factors responsible for an increased conjunctival swab contamination risk. In addition, our investigation illustrated that a positive conjunctival swab is not a strong indicator for organ culture media contamination. Critical discussion is necessary regarding the validity of conjunctival swabs as prognostic parameters for organ culture media contamination.

Characterization of Islets from Chronic Calcific Pancreatitis Patients of Tropical Region with Distinct Phenotype

Background and Objective: Islet autotransplantation is performed to preserve endocrine function in patients undergoing pancreatic resections for painful chronic pancreatitis. We characterized islets isolated from chronic pancreatitis patients (CP) of tropical region. Patients and Methods: Pancreatic tissues were obtained from CP patients with and without diabetes undergoing pancreatic resections (n = 35) and brain-dead multi organ donors (n = 6; considered as controls). Islets isolated were assessed for yield, purity, viability and in vitro islet function (Glucose stimulated insulin release, GSIR) as per standard protocols. Results: Islets from CP patients without diabetes were similar to controls in yield (control 4120 - 6100 IE/g, CP 3550 - 5660 IE/g), purity (control 78% ± 12%, CP 70% ± 8.2%) and viability (control 85% ± 8%, CP 81% ± 10%) and islets from CP patients with diabetes showed decreases in yield (3002 - 2300 IE/g), purity (61% ± 16%) and viability (62% ± 21%). Islets measuring 50 - 200 μ were similar in abundance in controls (94.74% ± 3.2%) and CP patients with and without diabetes, 86.31% ± 4.9%, 91.03% ± 3.8%. GSIR of islets from CP patients and controls were similar at 5.5 mM glucose (2.8 - 3.1 μU/ml). However, GSIR at 16.5 mM glucose was decreased in CP patients (control 18.5 ± 0.6, CP without diabetes 11.8 ± 0.3, CP with diabetes 4.3 ± 0.3 μU/ml). Conclusion: Our results demonstrate suitability of islets isolated from CP patients of tropical region for autotransplantation.

Improvement in Renal Function After Late Conversion to Sirolimus-Based Immunosuppression in Composite Tissue Allotransplantation

Improvement in Renal Function After Late Conversion to Sirolimus-Based Immunosuppression in Composite Tissue Allotransplantation

Human Uterus Retrieval From a Multi-Organ Donor

To determine if a uterus can be retrieved for reproductive organ transplantation and to describe the surgical technique. We participated in a local organ donor network retrieval team for over 6 months. Heart-beating, brain-dead multi-organ donors were identified through an existing donor network following routine protocols. After institutional review board and organ donor network approval of the uterus transplantation project, approximately 1,800 eligible organ donors were identified as required by legislation. Multi-organ procurement surgery took place in approximate 150 of these, with nine specifically consented for the uterus retrieval. Regularly performed multi-organ transplantation retrievals included the uterus without complications in eight donors. Pedicles used included the ovarian, uterine, or internal iliac vessels. After retrieval, serial histology sections throughout the period of cold ischemia, taken every 15-30 minutes, showed no signs of change over 12 hours of cold ischemia. The human uterus can be obtained from local organ donor networks using existing protocols. III.

Vascular Tissue Banking: State of the Art

Introduction The cardiovascular homograft banks in Italy were set up in 1994 in Milan (Lombardia) and Treviso (Veneto) and in 2001 in Bologna, Emilia Romagna. In this study we briefly summarize the data from Emilia Romagna Cardiovascular Tissue Bank. Material and Methods In Emilia Romagna, vascular homografts were harvested from brain-dead multiorgan donors (aged 15–55 years) by a dedicated vascular surgery team. All donors were virologically screened for human immunodeficiency virus (HIV), hepatitis B and C, Treponema pallidum, cytomegalovirus (CMV), and Toxoplasma. After transferring the vascular homografts to Emilia Romagna Cardiovascular Tissue Bank facilities, the arteries were prepared, classified (class III to I), and transferred to an antibiotic-containing solution under a laminar flow cabinet. After the decontamination, all homografts were cryopreserved and stored in the vapour phase of liquid nitrogen. Microbiological tests were performed in all phases of preparation. Samples were routinely taken from 1 vessel and formalin fixed for the histology. Bags with cryopreserved homografts were sent in dry ice to the hospitals when required and thawing protocol of the Bank was included. Results and Conclusions From January 2002 to October 2004, 543 homografts from 125 heart-beating donors were harvested and transferred to Emilia Romagna Cardiovascular Tissue Bank. After preparation, 459 of 543 (85%) were cryopreserved and stored. Vascular homografts classified class I were discarded. Other criteria of rejection were: (1) positive serology, and (2) persistent positive microbiology after decontamination. From March 2002, 333 cryopreserved homografts were assigned to several vascular surgery departments in Italy. The assessment of 3-year activity of Emilia Romagna Cardiovascular Tissue Bank might be used as an indicator of the efficiency of selecting, cryopreserving, and allocating quality-controlled vascular homografts.

Preservation of Vein Allograft Viability during Long-Term Storage

Background: The aim of this study was to compare the vein allograft viability following cryopreservation with that remaining after prolonged refrigerated storage. Materials and Methods: Great saphenous vein biopsies had been cryopreserved, and the samples were divided into two matched groups and stored in tissue culture medium for 42 days at +4°C, either with or without regular medium replacement. Each vein allograft was biopsied and assayed for viability every third day by the methyltetrazolium reduction assay. Viability indexes of vein allografts harvested from brain-dead multi-organ donors and from cadavers whose warm ischemic periods were maximally 24 h were also compared. Results: Vein allografts stored for 42 days at +4°C showed a similar viability (58.9 ± 1.2%) to that of cryopreserved veins (59.7 ± 2.3%). This was true even when cryopreserved and thawed allografts were subjected to 3 days of post-thaw incubation under presumably favorable conditions (58.7 ± 1.6%). There was no viability index difference between the samples with medium replaced and not replaced and the specimens harvested from two different donor groups. Conclusions: Long-term storage of vein allografts at +4°C is a valuable option for regular banking practice. Sufficient amounts can be procured from cadavers similar to tissue donors.

Value of cardiac troponin I and T for selection of heart donors and as predictors of early graft failure.

Cardiac troponin I and T (cTnI and cTnT) are sensitive and specific markers of myocardial damage. We evaluated them for the selection of heart donors and as predictors of early graft failure after heart transplantation. cTnI, cTnT, myoglobin, and creatine kinase (CK) levels and its isoenzyme MB (CKMB) activity and mass were measured in serum samples immediately before opening the pericardium from 126 consecutive brain-dead multi-organ donors over 10 years of age inspected by our harvesting team. Donors with serum creatinine >2.0 mg/dL (n=6) were excluded from the analysis. Donors for high-urgency status recipients (n=2) were also excluded. The remaining donors were retrospectively divided into three groups: group I (n=68), grafts with good function; group II (n=11), grafts with impaired function; and group III (n=39), grafts not accepted for transplantation. No differences in donor and recipient characteristics were found among the groups. The mean values of cTnI (0.36+/-0.88 microg/L, 4.45+/-3.28 microg/L, and 3.02+/-7.88 micog/L, respectively) and cTnT (0.016+/-0.029 microg/L, 0.134+/-0.114 microg/L, and 0.123+/-0.245 microg/L, respectively) were lower in group I when compared with groups II or III (cTnI: P<0.0001, P=0.018; cTnT: P<0.0001, P=0.012). The cTnI value was higher in group II compared with group III (P=0.023). The cTnT values were similar in groups II and III. A cTnI value >1.6 microg/L as a predictor of early graft failure had a specificity of 94%, and a cTnT value of >0.1 microg/L had a specificity of 99%. The odds ratio for the development of acute graft failure after heart transplantation was 42.7 for donors with cTnI >1.6 microg/L and 56.9 for donors with cTnT >0.1 microg/L. No differences of myoglobin, CKMB activity, or CKMB/CK ratio were found among the groups. Significantly higher cTnI and cTnT values were found in peripheral blood at the time of explantation in donors of hearts with subsequently impaired graft function and in not accepted donors. cTnI and cTnT are useful as additional parameters for heart donor selection.

Primary aortic valve replacement with allografts over twenty-five years: Valve-related and procedure-related determinants of outcome

Objectives: Allografts offer many advantages over prosthetic valves, but allograft durability varies considerably. Methods: From 1969 through 1993, 618 patients aged 15 to 84 years underwent their first aortic valve replacement with an aortic allograft. Concomitant surgery included aortic root tailoring (n = 58), replacement or tailoring of the ascending aorta (n = 56), and coronary artery bypass grafting (n = 87). Allograft implantation was done by means of a “freehand” subcoronary technique (n = 551) or total root replacement (n = 67). The allografts were antibiotic sterilized (n = 479), cryopreserved (n = 12), or viable (unprocessed, harvested from brain-dead multiorgan donors or heart transplant recipients, n = 127). Maximum follow-up was 27.1 years. Results: Thirty-day mortality was 5.0%, and crude survival was 67% and 35% at 10 and 20 years. Ten- and 20-year rates of freedom from complications were as follows: endocarditis, 93% and 89%; primary tissue failure, 62% and 18%; and redo aortic valve replacement, 81% and 35%. Multivariable Cox analyses identified several valve- and procedure-related determinants: rising allograft donor age and antibiotic-sterilized allograft for mortality; donor more than 10 years older than patient for endocarditis; rising donor age minus patient age, rising implantation time (from harvest to aortic valve replacement), and donor age more than 65 years for tissue failure; and rising donor age minus patient age, young patient age, rising implantation time, and subcoronary implantation preceded by aortic root tailoring for redo aortic valve replacement. Estimated 10- and 20-year rates of freedom from tissue failure for a 70-year-old patient with a viable valve from a 30-year-old donor and no other risk factors were 91% and 64%; the figures were 71% and 20% if the donor age was 65 years. The rates of freedom from tissue failure for a 30-year-old patient with a 30-year-old donor were 82% and 39%; the figures were 49% and 3% with a 65-year-old donor. Beneficial influences of a viable valve were largely covered by short harvest time (no delay for allografts from brain dead organ donors or heart transplant recipients) and short implantation time. Conclusions: Primary allograft aortic valve replacement can give acceptable results for up to 25 years. The late results can be improved by the use of a viable allograft, by matching patient and donor age, and by more liberal use of free root replacement with re-implantation of the coronary arteries rather than tailoring the root to accommodate a subcoronary implantation. (J Thorac Cardiovasc Surg 1999;117:77-91)

Donor thyroid function does not affect outcome in orthotopic liver transplantation.

Brainstem death is associated with endocrine and metabolic alterations that can result in donor hemodynamic instability. It has been suggested that these changes can be reversed through hormonal manipulation of the donor. We measured thyroid hormone levels (free triiodothyronine [fT3], free tetraiodothyronine [fT4], reverse triiodothyronine) and thyroid-stimulating hormone (TSH) in 50 consecutive adult brain dead multiorgan donors. Recipient graft function was assessed using peak and day 5 aspartate aminotransferase, peak serum bilirubin, and minimum prothrombin time during the first week after OLT. Free T3 was low in 32/50 donors and was associated with a low fT4 in 24 cases. TSH was normal in 35 donors and we found no correlation between TSH levels and fT3 or fT4. Reverse triiodothyronine was normal or high in 96% of donors. Patient and graft survival were 96% for both the low and high fT3 groups. These data suggest that euthyroid sick syndrome is the most likely cause for the endocrine and metabolic alterations seen in brainstem-dead donors. This does not appear to influence liver recipient or graft survival.