Brain Death Group Research Articles

Angiotensin-converting enzyme 2 activation attenuates inflammation and oxidative stress in brain death donor followed by rat lung transplantation

Brain death (BD) provides most of the donor organs destined for lung transplantation (LTx). However, the organs may be affected by inflammatory and oxidative processes. Based on this, we hypothesize that the angiotensin-converting enzyme 2 (ACE2) activation can reduce the lung injury associated with LTx. 3 h after BD induction, rats were injected with saline (BD group) or an ACE2 activator (ACE2a group; 15 mg/kg-1) and kept on mechanical ventilation for additional 3 h. A third group included a control ventilation (Control group) prior to transplant. After BD protocol, left LTx were performed, followed by 2 h-reperfusion. ACE2 activation was associated with better oxygenation after BD management (p = 0.01), attenuating edema (p = 0.05) followed by the reduction in tissue resistance (p = 0.01) and increase of respiratory compliance (p = 0.02). Nrf2 expression was also upregulated in the ACE2a group (p = 0.03). After transplantation, ACE2a group showed lower levels of TNF-α (p = 0.02), IL-6 (p = 0.001), IL-1β (p = 0.01), ROS (p = 0.004) and MDA (p = 0.002), in addition to higher CAT activity (p = 0.04). In conclusion, our study suggests that ACE2 activation improves anti-inflammatory and antioxidant activity in a model of LTx.

Anti-inflammatory effect of thalidomide in an experimental lung donor model of brain death.

Lung transplantation stands as a vital treatment for severe lung diseases, primarily sourcing organs from donors with brain death (BD). This research delved into the potential anti-inflammatory effects of thalidomide in rats with BD-induced lung complications. In this study twenty-four Wistar rats were divided into three groups: the control (CTR), brain death (BD) and brain death + thalidomide (TLD) groups. Post specific procedures, a 360min monitoring period ensued. Comprehensive analyses of blood and heart-lung samples were conducted. Elevated IL-6 levels characterized both BD and TLD groups relative to the CTR (p = 0.0067 and p = 0.0137). Furthermore, TNF-α levels were notably higher in the BD group than both CTR and TLD (p = 0.0152 and p = 0.0495). Additionally, IL-1β concentrations were significantly pronounced in both BD and TLD compared to CTR, with the BD group surpassing TLD (p = 0.0256). Immunohistochemical assessments revealed augmented NF-ĸB expression in the BD group in comparison to both CTR and TLD (p = 0.0006 and p = 0.0005). With this study we can conclude that BD induced acute pulmonary inflammation, whereas thalidomide manifested a notable capability in diminishing key inflammatory markers, indicating its prospective therapeutic significance in lung transplantation scenarios.

Male versus female inflammatory response after brain death model followed by ex vivo lung perfusion

BackgroundEx vivo lung perfusion (EVLP) is a useful tool for assessing lung grafts quality before transplantation. Studies indicate that donor sex is as an important factor for transplant outcome, as females present higher inflammatory response to brain death (BD) than males. Here, we investigated sex differences in the lungs of rats subjected to BD followed by EVLP.MethodsMale and female Wistar rats were subjected to BD, and as controls sham animals. Arterial blood was sampled for gas analysis. Heart–lung blocks were kept in cold storage (1 h) and normothermic EVLP carried out (4 h), meanwhile ventilation parameters were recorded. Perfusate was sampled for gas analysis and IL-1β levels. Leukocyte infiltration, myeloperoxidase presence, IL-1β gene expression, and long-term release in lung culture (explant) were evaluated.ResultsBrain dead females presented a low lung function after BD, compared to BD-males; however, at the end of the EVLP period oxygenation capacity decreased in all BD groups. Overall, ventilation parameters were maintained in all groups. After EVLP lung infiltrate was higher in brain dead females, with higher neutrophil content, and accompanied by high IL-1β levels, with increased gene expression and concentration in the culture medium (explant) 24 h after EVLP. Female rats presented higher lung inflammation after BD than male rats. Despite maintaining lung function and ventilation mechanics parameters for 4 h, EVLP was not able to alter this profile.ConclusionIn this context, further studies should focus on therapeutic measures to control inflammation in donor or during EVLP to increase lung quality.

Using extracorporeal membrane oxygenation in donations after cardiac death or brain death: A single-center experience and long-term outcome.

The use of extended criteria donors is a routine practice that sometimes involves extracorporeal membrane oxygenation (ECMO) in donations after cardiac death or brain death. We performed a retrospective study in a single center from January 2006 to December 2019. The study included 90 deceased donor liver transplants. The patients were divided into three groups: the donation after brain death (DBD) group (n = 58, 64.4%), the DBD with ECMO group (n = 11, 12.2%) and the donation after cardiac death (DCD) with ECMO group (n = 21, 23.3%). There were no significant differences between the DBD with ECMO group and the DBD group. When comparing the DCD with ECMO group and the DBD group, there were statistically significant differences for total warm ischemia time (p < 0.001), total cold ischemia time (p = 0.023), and split liver transplantation (p < 0.001), and there was significantly poor recovery in regard to total bilirubin level (p = 0.027) for the DCD with ECMO group by repeated measures ANOVA. The 5-year survival rates of the DBD, DBD with ECMO, and DCD with ECMO groups were 78.1%, 90.9%, and 75.6%, respectively. The survival rate was not significantly different when comparing the DBD group to either the DBD with ECMO group (p = 0.435) or the DCD with ECMO group (p = 0.310). Using ECMO in donations after cardiac death or brain death is a good technology, and it contributed to 35.6% of the liver graft pool.

Transplantation Outcomes with Donor Hearts after Circulatory Death

BackgroundData showing the efficacy and safety of the transplantation of hearts obtained from donors after circulatory death as compared with hearts obtained from donors after brain death are limited.MethodsWe conducted a randomized, noninferiority trial in which adult candidates for heart transplantation were assigned in a 3:1 ratio to receive a heart after the circulatory death of the donor or a heart from a donor after brain death if that heart was available first (circulatory-death group) or to receive only a heart that had been preserved with the use of traditional cold storage after the brain death of the donor (brain-death group). The primary end point was the risk-adjusted survival at 6 months in the as-treated circulatory-death group as compared with the brain-death group. The primary safety end point was serious adverse events associated with the heart graft at 30 days after transplantation.ResultsA total of 180 patients underwent transplantation; 90 (assigned to the circulatory-death group) received a heart donated after circulatory death and 90 (regardless of group assignment) received a heart donated after brain death. A total of 166 transplant recipients were included in the as-treated primary analysis (80 who received a heart from a circulatory-death donor and 86 who received a heart from a brain-death donor). The risk-adjusted 6-month survival in the as-treated population was 94% (95% confidence interval [CI], 88 to 99) among recipients of a heart from a circulatory-death donor, as compared with 90% (95% CI, 84 to 97) among recipients of a heart from a brain-death donor (least-squares mean difference, −3 percentage points; 90% CI, −10 to 3; P<0.001 for noninferiority [margin, 20 percentage points]). There were no substantial between-group differences in the mean per-patient number of serious adverse events associated with the heart graft at 30 days after transplantation.ConclusionsIn this trial, risk-adjusted survival at 6 months after transplantation with a donor heart that had been reanimated and assessed with the use of extracorporeal nonischemic perfusion after circulatory death was not inferior to that after standard-care transplantation with a donor heart that had been preserved with the use of cold storage after brain death. (Funded by TransMedics; ClinicalTrials.gov number, NCT03831048.)

Evaluation of Optic Nerve Sheath Diameter for Prediction of the Development of Brain Death in Patients Admitted to the Intensive Care Unit with Intracranial Hemorrhage

Intracranial hemorrhage results in an increase in intracranial pressure, which is considered to be the leading cause of brain death. Follow-up of these patients and early recognition of possible brain death are important for organ donation. It has been shown that increased intracranial pressure is proportional to the changes in optic nerve sheath diameter. The aim of this study was to investigate the usability of changes in optic nerve sheath diameter secondary to increased intracranial pressure as a precursor for identification of patients who will develop brain death. Patients admitted to the intensive care unit with intracranial hemorrhage and a Glasgow Coma Scale score of 7 or less were divided into 3 groups: brain death group (patients with brain death), hemorrhage group (patients who died due to hemorrhage), and survivor group (patients who were discharged from the intensive care unit). Optic nerve sheath diameter was measured by computed tomography taken at admission. The highest value for optic nerve sheath diameter was measured in the brain death group (P < .001). The cutoff point for optic nerve sheath diameter to predict the presence of brain death was determined as >6.62 mm. The area underthe curve for optic nerve diameter was 0.85 (sensitivity 66.20%, specificity 90%; P < .001). The results showed a 25.529- fold increased risk of brain death in measurements above this value. An optic nerve sheath diameter value of >6.62 mm measured on initial cranial computed tomography of patients admitted to the intensive care unit with a diagnosis of intracranial hemorrhage is indicative of an increased risk of brain death.

Early prediction model of brain death in out-of-hospital cardiac arrest patients: a single-center retrospective and internal validation analysis

BackgroundA shortage of donor organs amid high demand for transplantable organs is a worldwide problem, and an increase in organ donation would be welcomed by the global healthcare system. Patients with brain death (BD) are potential organ donors, and early prediction of patients with BD may facilitate the process of organ procurement. Therefore, we developed a model for the early prediction of BD in patients who survived the initial phase of out-of-hospital cardiac arrest (OHCA).MethodsWe retrospectively analyzed data of patients aged < 80 years who experienced OHCA with a return of spontaneous circulation (ROSC) and were admitted to our hospital between 2006 and 2018. We categorized patients into either a non-BD or BD group. Demographic and laboratory data on ED admission were used for stepwise logistic regression analysis. Prediction scores of BD after OHCA were based on β-coefficients of prognostic factors identified in the multivariable logistic model.ResultsOverall, 419 OHCA patients with ROSC were admitted to our hospital during the study period. Seventy-seven patients showed BD (18.3%). Age and etiology of OHCA were significantly different between the groups. Logistic regression analysis confirmed that age, low-flow time, pH, and etiology were independent predictors of BD. The area under the receiver operating characteristic curve for this model was 0.831 (95% confidence interval, 0.786–0.876).ConclusionsWe developed and internally validated a new prediction model for BD after OHCA, which could aid in the early identification of potential organ donors for early donor organ procurement.

MG132 protects against lung injury following brain death in rats.

Brain death (BD) results in injury to organs and induces lung donor dysfunction. Since the 20S proteasome abnormality is associated with a variety of diseases, the present study investigated whether it was involved in lung injury following BD in rats, and the effects of the proteasome inhibitor MG132 on lung injury was also assessed. Rats were assigned to a BD group or a control sham group. The BD group of rats were sacrificed at different time points after BD. Administration of MG132 was performed intraperitoneally 30 min before BD. Arterial blood was drawn to measure the oxygenation index [partial artery pressure of oxygen (PaO2)/fractional concentration of inspired oxygen (FiO2)]. The right lung was used for staining with hematoxylin and eosin, immunohistochemistry, immunofluorescence, western blotting and RT-qPCR analysis. The left lung was used to measure the wet and dry weights. Rat alveolar macrophages (NR8383) were treated with MG132 and hypoxia/reoxygenation (H/R) and used for western blotting and flow cytometry. The PaO2/FiO2 ratio decreased after BD; the wet/dry weight ratio, histological lung injury score and protein expression of 20S proteasome β1 and inducible nitric oxide synthase (iNOS) gradually increased in rats after BD. Colocalization in the immunofluorescence between 20S proteasome β1 and iNOS was observed. MG132 treatment increased the PaO2/FiO2 ratio and decreased the wet/dry weight ratio, histological lung injury score and protein expression of 20S proteasome β1 and iNOS in rats after BD. MG132 was revealed to increase NR8383 apoptosis after H/R and to upregulate the protein expression levels of p-JNK and cleaved-caspase 3. Overall, the proteasome inhibitor MG132 could effectively reduce lung injury, which may be associated with its ability to inhibit the expression of the proteasome and promote the apoptosis of alveolar macrophages.

217.9: Activation of Angiotensin-converting Enzyme 2 (ACE2) Modulates Lung Mechanics in a Brain Death Model and Attenuates Pulmonary Edema After Rat Lung Transplantation

Introduction: Lung transplantation is a therapeutic option established worldwide for end-stage lung diseases. However, as most donors evolve with brain death (BD), the donated lung may have been compromised. In view of the participation of the renin angiotensin system (RAS) and the use of angiotensin-converting enzyme 2 (ACE2) activators in several pathological processes, it was investigated how diminazene aceturate (DIZE), an ACE2 activator, modulates hemodynamic and blood gas changes, as well as lung function following transplantation in rats. Method: Male Lewis rats were randomly distributed in the following experimental groups: intact, brain death (BD) and BD + diminazene aceturate (BD+DIZE). The last two groups were submitted to brain death process, treated with saline (0.9%) or DIZE (15 mg/kg-1) and kept on mechanical ventilation for 6 hours (donor). After this period, cardiopulmonary block extraction and left unilateral transplantation (LTx) with independent graft ventilation was performed, followed by 2h reperfusion. Hemodynamics (mean arterial pressure - MAP), blood gas analysis, lung mechanics, and pulmonary edema were evaluated. Results are presented as S.E.M. (ANOVA; Tukey; p<0.05). (Approval # CEUA/FMUSP - 1630/2021). Results: The administration of DIZE, 3 hours after BD, prevented the increase in the MAP (210’ after BD-induction: BD – 110 ± 12 mmHg; n=5; BD+DIZE – 40 ± 12 mmHg; n=4/ p=0.0001) without associated blood gas and metabolic alterations. Changes in lung mechanics, such as decreased tissue damping (G) and histeresivity (n) followed by increased respiratory system compliance (Crs), were associated with BD+DIZE (G - 0,25 ± 0,03 cmH2O/mL; Crs - 0,71 ± 0,03 mL/cmH2O; n – 0,14 ± 0,008) compared to intact (G - 0,40 ± 0,02 cmH2O/mL, p = 0.01; Crs – 0,64 ± 0,01 mL/cmH2O, p = 0.02; n - 0,26 ± 0,01, p = 0.004) and BD groups (G – 0,41± 0,05 cmH2O/mL, p = 0.02; Crs – 0,61 ± 0,01 mL/cmH2O, p = 0.01; n - 0,25 ± 0,008, p = 0.01) (Figure 1). After LTx, MAP, gas exchange function, and lung mechanical parameters, were not different among the 3 groups (p>0.05). On the other hand, the DIZE treatment was capable to reduce wet-to-dry weight ratio (INTACT – 1,87 ± 0,13; BD – 2,59 ± 0,14; BD+DIZE – 1,93 ± 0,15/ p=0.01) (Figure 2). Conclusion: Our data suggests that activation of ACE2 is able to modulate donor hemodynamic and lung mechanical parameters, probably reducing tissue resistance and improving airflow in the peripheral airways, converging to a decrease in ventilation heterogeneity in the sudden onset model of brain death. Our data also indicates that DIZE attenuates pulmonary edema on grafts from BD donors after lung transplantation. Keywords: Diminazene aceturate. Renin-angiotensin system. Brain death. Lung mechanics. Lung transplantation.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico.

Brain Death and Its Prediction in Out-of-Hospital Cardiac Arrest Patients Treated with Targeted Temperature Management.

Evolution toward brain death (BD) in out-of-hospital cardiac arrest patients with targeted temperature management (TTM) provides opportunities for organ donation. However, knowledge regarding BD in these patients is limited. We retrospectively analyzed the TTM registry of one hospital where life-sustaining therapy was not withdrawn. In-hospital death patients were categorized into BD and non-BD groups. We explored the process of evolution toward BD and its predictors by comparing the serial measurements of clinical variables and the results of various prognostic tests between the two groups. Of the 121 patients who died before hospital discharge, 19 patients (15.7%) developed BD at a median of 6 (interquartile range, 5.0–7.0) days after cardiac arrest. Four patients with pupillary light reflexes at 48 h eventually developed BD. The area under the curves of the gray-to-white matter ratio (GWR) on early brain computed tomography images and the level of S100 calcium-binding protein B (S100B) at 72 h were 0.67 (95% CI, 0.55–0.77) and 0.70 (95% CI, 0.55–0.83), respectively. In conclusion, approximately one-sixth of all in-hospital deaths were diagnosed with BD at a median of 6 days after cardiac arrest. The use of GWR and serial S100B measurements may help to screen potential BD.

Donor Death Category Is an Effect Modifier Between Cold Ischemia Time and Post-transplant Graft Function in Deceased-Donor Kidney Transplant Recipients.

Objectives: We aimed to analyze the effect of cold ischemia time (CIT) on post-transplant graft function through mixed-effect model analysis to reduce the bias caused by paired mate kidneys.Methods: We reviewed all kidney transplantation records from 2015 to 2019 at our center. After applying the exclusion criteria, 561 cases were included for analysis. All donor characteristics, preservation and matching information, and recipient characteristics were collected. Transplant outcomes included delayed graft function (DGF) and estimated glomerular filtration rate (eGFR). Generalized linear mixed models were applied for analysis. We also explored potential effect modifiers, namely, donor death category, expanded criteria donors, and donor death causes.Results: Among the 561 cases, 79 DGF recipients developed DGF, and 15 recipients who died after surgery were excluded from the eGFR estimation. The median stable eGFR of the 546 recipients was 60.39 (47.63, 76.97) ml/min/1.73 m2. After adjusting for confounding covariates, CIT had a negative impact on DGF incidence [odds ratio = 1.149 (1.006, 1.313), P = 0.041]. In the evaluation of the impact on eGFR, the regression showed that CIT had no significant correlation with eGFR [β = −0.287 (−0.625, 0.051), P = 0.096]. When exploring potential effect modifiers, only the death category showed a significant interaction with CIT in the effect on eGFR (Pinteraction = 0.027). In the donation after brain death (DBD) group, CIT had no significant effect on eGFR [β = 0.135 (−0.433, 0.702), P = 0.642]. In the donation after circulatory death/donation after brain death followed by circulatory death (DCD/DBCD) group, CIT had a significantly negative effect on eGFR [β= −0.700 (−1.196, −0.204), P = 0.006]. Compared to a CIT of 0–6 h, a CIT of 6–8 or 8–12 h did not decrease the post-transplant eGFR. CIT over 12 h (12–16 h or over 16 h) significantly decreased eGFR. With the increase in CIT, the regenerated eGFR worsened (Ptrend = 0.011).Conclusion: Considering the effect of paired mate kidneys, the risk of DGF increased with prolonged CIT. The donor death category was an effect modifier between CIT and eGFR. Prolonged CIT did not reduce the eGFR level in recipients from DBDs but significantly decreased the eGFR in recipients from DCDs/DBCDs. This result indicates the potential biological interaction between CIT and donor death category.

Hemoderivative Transfusion in Liver Transplantation: Comparison Between Recipients of Grafts From Brain Death Donors and Recipients of Uncontrolled Donors After Circulatory Death

Intraoperative bleeding during liver transplantation has been correlated with a higher risk of morbidity and mortality and decrease in patient and graft survival. Between January 2006 and December 2016 we performed 783 orthotopic liver transplants. After applying exclusion criteria, we found liver grafts from donors after circulatory death (DCD, group A) were used in 69 patients and liver grafts from donors after brain death (group B) were used in 265 patients. No difference was found in terms of sex, body mass index, Model for End-Stage Liver Disease score, indication for transplantation, intensive care unit stay, and Child-Pugh score. The mean transfusion of hemoderivates was as follows: red blood cell 9 (0-28) units in group A vs 6 (0-20) units in group B (P=.004) and fresh frozen plasma 10 (0-29) units in group A vs 9.5 (0-23) in group B (P=.000). The only 2 factors related to massive blood transfusion (>6 units of red blood cell) were uncontrolled DCD condition (odds ratio=2.38; 95% confidence interval, 1.32-4.31; P=.004), and higher Model for End-Stage Liver Disease score (odds ratio=2.63; 95% confidence interval, 1.53-4.55; P=.001). Survival at 1, 3, and 5 years was 81.3%, 70.2%, and 68.9% in group A vs 89%, 83.7%, and 78% in group B (P=.070). The use of liver grafts from DCDs is associated with increased necessity of transfusion of hemoderivates in comparison with the use of liver grafts from donors after brain death.

Cardiac MicroRNA Expression Profile After Experimental Brain Death Is Associated With Myocardial Dysfunction and Can Be Modulated by Hypertonic Saline.

Brain death (BD) is associated with systemic inflammatory compromise, which might affect the quality of the transplanted organs. This study investigated the expression profile of cardiac microRNAs (miRNAs) after BD, and their relationship with the observed decline in myocardial function and with the changes induced by hypertonic saline solution (HSS) treatment. Wistar rats were assigned to sham-operation (SHAM) or submitted to BD with and without the administration of HSS. Cardiac function was assessed for 6 h with left ventricular (LV) pressure-volume analysis. We screened 641 rodent miRNAs to identify differentially expressed miRNAs in the heart, and computational and functional analyses were performed to compare the differentially expressed miRNAs and find their putative targets and their related enriched canonical pathways. An enhanced expression in canonical pathways related to inflammation and myocardial apoptosis was observed in BD induced group, with 2 miRNAs, miR-30a-3p, and miR-467f, correlating with the level of LV dysfunction observed after BD. Conversely, HSS treated after BD and SHAM groups showed similar enriched pathways related to the maintenance of heart homeostasis regulation, in agreement with the observation that both groups did not have significant changes in LV function. These findings highlight the potential of miRNAs as biomarkers for assessing damage in BD donor hearts and to monitor the changes induced by therapeutic measures like HSS, opening a perspective to improve graft quality and to better understand the pathophysiology of BD. The possible relation of BD-induced miRNA's on early and late cardiac allograft function must be investigated.

Experimental Lung Donor Models for Transplant

<h3>Purpose</h3> The main types of accepted donations may be divided into: Donation after Brain Death and Donation after Circulatory Death. In addition to that, some important events are frequently associated to these two types of donors, such as Hemorrhagic Shock (HS) and Cold Ischemia (CI). These events also guide the standardization of the various experimental models developed by research groups for the employment of specific treatments: brain death (BD), circulatory death (CD), HS and CI. In this study, we aimed to describe and compare the lung mechanics and inflammatory process related to these four experimental models of lung donors. <h3>Methods</h3> Forty Sprague-Dawley rats were divided into 4 groups: BD (intracranial Fogarty balloon inflation), HS (hypovolemic protocol - 40 mmHg), CD (circulatory death + 3 h warm ischemia) and CI (6 h cold ischemia). Inflammatory responses and edema were assessed. In addition to these, as the BD and HS rats were kept hemodynamically stable for six hours, monitoring of lung mechanics was possible. <h3>Results</h3> Six hours after the induction of the HS, increase in elastance and resistance were observed (fig. 1). In lung tissue, BD and HS presented high levels of IL-1β and IL-6 in comparison to the CD and CI groups. In contrast, IL-10 levels were higher in the HS group, being significantly different when compared to the CD group. Finally, the BD group had the highest lung wet-to-dry ratio (fig. 2). <h3>Conclusion</h3> The experimental model of HS cause dysfunction of the lung mechanics. BD and HS lead to increased levels of cytokines and lung edema. These differences should be carefully considered to choose the ideal experimental model for developing specific therapeutic strategies.

A Single-Center Analysis of Survival Outcome between Donor after Cardiac Death and Donor after Brain Death

<h3>Purpose</h3> Donor after cardiac death (DCD) is an organ procurement method that is being increasingly used to expand the current lung donor pool. We hypothesize that in our single-center study, DCD and donor after brain death (DBD) groups would have similar survival rates as found in previous studies. <h3>Methods</h3> A retrospective analysis was performed at a single center which identified 801 lung transplants completed between March 2012 and September 2020. DCD LTx patients (n=18) were matched by propensity scores with donors after brain death DBD recipients. Propensity scores (PS) were determined using patient age, sex, race diagnosis, BMI, and donor age. PS matching was done by comparing 1:1, 1:2, and 1:3 pooled groups (DCD:DBD), and performing either chi-squared or t-tests analyses on each variable before and after matching. Survival outcomes were calculated using Kaplan-Meier curves and log-rank tests. <h3>Results</h3> Of the 801 LTx patients, mean donor age for DCD lungs was 27.59. The PS matched DBD group did not significantly differ from the DCD group in age (p=0.6339), sex (p=0.401), race (p=0.846), diagnosis (p=0.102), pump use (p=0.867), BMI (p=0.0467) or donor age (p=0.8275). Log-rank testing with Kaplan-Meier curves of pre-PS matching revealed no significant survival difference between DCD and DBD groups (p=0.38). The PS matched data similarly found no significant difference in patient survival (p=0.26) which was consistent across the 1:1, 1:2 and 1:3 matched groups. <h3>Conclusion</h3> Our study found both DBD and DCD donor lungs provide comparable short-term survival outcomes. This is in agreement with previous studies, which argue for the viability of DCD donor lungs and for their use to be expanded.

Non-invasive Evaluation of Brain Death Caused by Traumatic Brain Injury by Ultrasound Imaging.

ObjectivesTo investigate the clinical value of non-invasive ultrasound imaging in the evaluation of brain death caused by traumatic brain injury.MethodsThirty-four patients with acute severe traumatic brain injury were admitted to hospital within 48 h after injury. All patients were monitored intracranial pressure, transcranial Doppler, echocardiography examination, collection intracranial pressure, MCA-Vs, MCA-Vd, MCA-Vm, EF, LVMPI, RVMPI and other indicators, and combined with clinical conditions and other related data for comparative study and statistical analysis.ResultsThe blood flow spectrum was characterized by diastolic retrograde blood flow spectrum pattern and nail waveform spectrum shape when the patient had clinical brain death. For the parameters of transcranial Doppler, there were significant differences in MCA-Vm and PI between clinical brain death group and normal control group (P < 0.05). For the parameters of echocardiography, there were statistically significant differences in EF, LVMPI, and RVMPI between clinical brain death group and normal control group (P < 0.05).ConclusionNon-invasive dynamic monitoring of cerebral hemodynamics and cardiac function parameters in patients with severe craniocerebral injury can provide a high accuracy and reliability for the preliminary diagnosis of brain death in patients with severe craniocerebral injury. It is helpful for early evaluation of prognosis and provides effective monitoring methods and guidance for clinical treatment.

Endoplasmic reticulum stress induces liver cells apoptosis after brain death by suppressing the phosphorylation of protein phosphatase 2A.

The present study aimed to investigate whether brain death (BD) induces the activation of endoplasmic reticulum stress (ERS) and protein phosphatase 2A (PP2A), and reveal the possible association with BD-induced liver cell apoptosis. A total of 30 healthy adult male Sprague-Dawley rats were randomized into three groups: Sham-operated group (S), BD group and 4-phenylbutyric acid group (BD + 4-PBA), with 10 rats in each group. All rats were anesthetized. The model of BD was established by inflating a balloon catheter that was placed into the extradural space after anesthesia. 4-PBA was administered via an intraperitoneal injection when the BD model was established. Anesthesia of the S group of rats was maintained for 6 h. Liver tissues were harvested after 6 h of BD. HE staining was used to evaluate the damage of liver. Terminal deoxynucleotidyl transferase-mediated 2′-deoxyuridine 5′-triphosphate nick-end labeling staining was used to observe the apoptosis of liver cells. Activation of ERS and PP2A was examined by western blotting and immunohistochemical staining. We reported that the apoptosis of liver cells after BD was significantly promoted than in the S group. Activation of ERS and PP2A was induced in the BD group when compared with S group. Phosphorylation of PP2A was suppressed in BD group. Application of 4-PBA decreased the activation of ERS and apoptosis rate compared with the BD group. In addition, activation of PP2A in the BD + 4-PBA group was decreased due to the reduction of PP2A phosphorylation compared with the BD group, but the levels were higher than in the S group. (P<0.05). In summary, our results indicated that BD induced ERS, then activated PP2A by suppressing the phosphorylation of PP2A, resulting in the apoptosis of liver cells.

Computed tomography angiography accuracy in brain death diagnosis.

The present study was designed to answer several concerns disclosed by systematic reviews indicating no evidence to support the use of computed tomography angiography (CTA) in the diagnosis of brain death (BD). Therefore, the aim of this study was to assess the effectiveness of CTA for the diagnosis of BD and to define the optimal tomographic criteria of intracranial circulatory arrest. A unicenter, prospective, observational case-control study was undertaken. Comatose patients (Glasgow Coma Scale score ≤ 5), even those presenting with the first signs of BD, were included. CTA scanning of arterial and venous vasculature and transcranial Doppler (TCD) were performed. A neurological determination of BD and consequently determination of case (BD group) or control (no-BD group) was conducted. All personnel involved with assessing patients were blinded to further tests results. Accuracy of BD diagnosis determined by using CTA was calculated based on the criteria of bilateral absence of visualization of the internal cerebral veins and the distal middle cerebral arteries, the 4-point score (4PS), and an exclusive criterion of absence of deep brain venous drainage as indicated by the absence of deep venous opacification on CTA, the venous score (VS), which considers only the internal cerebral veins bilaterally. A total of 106 patients were enrolled in this study; 52 patients did not have BD, and none of these patients had circulatory arrest observed by CTA or TCD (100% specificity). Of the 54 patients with a clinical diagnosis of BD, 33 met the 4PS (61.1% sensitivity), whereas 47 met the VS (87% sensitivity). The accuracy of CTA was time related, with greater accuracy when scanning was performed less than 12 hours prior to the neurological assessment, reaching 95.5% sensitivity with the VS. CTA can reliably support a diagnosis of BD. The criterion of the absence of deep venous opacification, which can be assessed by use of the VS criteria investigated in this study, can confirm the occurrence of cerebral circulatory arrest.Clinical trial registration no.: 12500913400000068 (clinicaltrials.gov).

Rapid or Slow Time to Brain Death? Impact on Kidney Graft Injuries in an Allotransplantation Porcine Model.

The use of donors deceased after brain death (DBD) with extended criteria in response to the shortage of grafts leads to the removal of more fragile kidneys. These grafts are at greater risk of not being grafted or delayed function. A better knowledge of the pathophysiology of DBDs would improve this situation. There is a difference between the results from animal models of DBD and the clinical data potentially explained by the kinetics of brain death induction. We compared the effect of the induction rate of brain death on the recovery of post-transplant renal function in a pig model of DBD followed by allografts in nephrectomized pigs. Resumption of early function post-transplant was better in the rapidly generated brain death group (RgBD) and graft fibrosis at three months less important. Two groups had identical oxidative stress intensity but a greater response to this oxidative stress by SIRT1, PGC1-α and NRF2 in the RgBD group. Modulation of mechanistic target of rapamycin (mTOR) stimulation by NRF2 would also regulate the survival/apoptosis balance of renal cells. For the first time we have shown that an allostatic response to oxidative stress can explain the impact of the rapidity of brain death induction on the quality of kidney transplants.

Hypertonic Saline Solution Reduces Microcirculatory Dysfunction and Inflammation in a Rat Model of Brain Death.

Brain death (BD) induces hemodynamic instability with microcirculatory hypoperfusion, leading to increased organ inflammation and dysfunction. This study investigated the effects of 7.5% hypertonic saline solution (HSS) on mesenteric microcirculatory dysfunction and inflammation in a rat model of BD. Male Wistar rats were anesthetized and mechanically ventilated. BD was induced by rapidly inflating an intracranial balloon catheter. The rats were randomly divided into: SH, sham-operated rats subjected to trepanation; NS, rats treated with NaCl 0.9%, 4 mL/kg immediately after BD; T1, rats treated with HSS (NaCl 7.5%, 4 mL/kg) immediately or 60 min after BD, T60. All groups were analyzed 180 min after the start of the experiment. Rats in BD groups presented with a similar hypertensive peak, followed by hypotension. Proportion of perfused small vessels was decreased in the NS group (46%) compared with the SH group (74%, P = 0.0039). HSS restored the proportion of perfused vessels (T1 = 71%, P = 0.0018). The anti-endothelial nitric oxide synthase (eNOS) protein expression significantly increased in rats given HSS (T1, and T60, P = 0.0002). Similar results were observed regarding endothelin-1 (P < 0.0001). Increased numbers of rolling (P = 0.0015) and migrated (P = 0.0063) leukocytes were observed in the NS group compared with the SH group. Rats given HSS demonstrated an overall reduction in leukocyte-endothelial interactions. The ICAM-1 levels increased in the NS group compared with the SH group, and decreased in the HSS-treated groups (P = 0.0002). HSS may improve the density of mesenteric perfused small vessels due to its effects on eNOS and endothelin-1 protein expression, and reduces inflammation by decreasing leukocyte adhesion and migration in a rat model of BD.