RESUMO
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 360 min 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-1ß 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.
Assuntos
Morte Encefálica , Talidomida , Ratos , Animais , Talidomida/farmacologia , Ratos Wistar , Morte Encefálica/metabolismo , Pulmão/metabolismo , Anti-Inflamatórios/farmacologiaRESUMO
Primary cell cultures are essential tools for elucidating the physiopathological mechanisms of the cardiovascular system. Therefore, a primary culture growth protocol of cardiovascular smooth muscle cells (VSMCs) obtained from human abdominal aortas was standardized. Ten abdominal aorta samples were obtained from patients diagnosed with brain death who were organ and tissue donors with family consent. After surgical ablation to capture the aorta, the aortic tissue was removed, immersed in a Custodiol® solution, and kept between 2 and 8 °C. In the laboratory, in a sterile environment, the tissue was fragmented and incubated in culture plates containing an enriched culture medium (DMEM/G/10% fetal bovine serum, L-glutamine, antibiotics and antifungals) and kept in an oven at 37 °C and 5% CO2. The aorta was removed after 24 h of incubation, and the culture medium was changed every six days for twenty days. Cell growth was confirmed through morphological analysis using an inverted optical microscope (Nikon®) and immunofluorescence for smooth muscle alpha-actin and nuclei. The development of the VSMCs was observed, and from the twelfth day, differentiation, long cytoplasmic projections, and adjacent cell connections occurred. On the twentieth day, the morphology of the VSMCs was confirmed by actin fiber immunofluorescence, which is a typical characteristic of VSMCs. The standardization allowed VSMC growth and the replicability of the in vitro test, providing a protocol that mimics natural physiological environments for a better understanding of the cardiovascular system. Its use is intended for investigation, tissue bioengineering, and pharmacological treatments.
Assuntos
Aorta Abdominal , Doenças Vasculares , Humanos , Morte Encefálica/metabolismo , Morte Encefálica/patologia , Músculo Liso Vascular/metabolismo , Doenças Vasculares/metabolismo , Doenças Vasculares/patologia , Modelos Teóricos , Miócitos de Músculo Liso , Encéfalo , Células CultivadasRESUMO
BACKGROUND: Clinical reports associate kidneys from female donors with worse prognostic in male recipients. Brain Death (BD) produces immunological and hemodynamic disorders that affect organ viability. Following BD, female rats are associated with increased renal inflammation interrelated with female sex hormone reduction. Here, the aim was to investigate the effects of sex on BD-induced Acute Kidney Injury (AKI) using an Isolated Perfused rat Kidney (IPK) model. METHODS: Wistar rats, females, and males (8 weeks old), were maintained for 4h after BD. A left nephrectomy was performed and the kidney was preserved in a cold saline solution (30 min). IPK was performed under normothermic temperature (37°C) for 90 min using WME as perfusion solution. AKI was assessed by morphological analyses, staining of complement system components and inflammatory cell markers, perfusion flow, and creatinine clearance. RESULTS: BD-male kidneys had decreased perfusion flow on IPK, a phenomenon that was not observed in the kidneys of BD-females (p < 0.0001). BD-male kidneys presented greater proximal (p = 0.0311) and distal tubule (p = 0.0029) necrosis. However, BD-female kidneys presented higher expression of eNOS (p = 0.0060) and greater upregulation of inflammatory mediators, iNOS (p = 0.0051), and Caspase-3 (p = 0.0099). In addition, both sexes had increased complement system formation (C5b-9) (p=0.0005), glomerular edema (p = 0.0003), and nNOS (p = 0.0051). CONCLUSION: The present data revealed an important sex difference in renal perfusion in the IPK model, evidenced by a pronounced reduction in perfusate flow and low eNOS expression in the BD-male group. Nonetheless, the upregulation of genes related to the proinflammatory cascade suggests a progressive inflammatory process in BD-female kidneys.
Assuntos
Injúria Renal Aguda , Transplante de Rim , Ratos , Feminino , Masculino , Animais , Morte Encefálica/metabolismo , Ratos Wistar , Rim/metabolismo , PerfusãoRESUMO
BACKGROUND: Vitamin D insufficiency is linked to several common inflammatory disorders. Brain death (BD) causes a massive catecholamine release, leading to intense inflammatory activity. We aimed to evaluate vitamin D serum levels in brain-dead individuals in comparison to critically ill patients without BD to assess the correlation between vitamin D and cytokine levels. METHODS: Sixteen brain-dead patients and 32 critically ill controls were prospectively enrolled. Blood samples from 25 brain-dead patients from a previous study were also used for vitamin D quantification. Plasma TNF, IL-1ß, IL-6, IL-8, IL-10, IFN-γ and serum vitamin D levels were compared using Student's t-test or one-way ANOVA. Spearman's test was used to assess the correlation between vitamin D and cytokine levels. RESULTS: Mean vitamin D levels were 16.4⯱â¯7.9â¯ng/mL, with 52 patients (71.2%) classified as vitamin D deficient (serum levelsâ¯<â¯20â¯ng/mL). Vitamin D levels were similar in 41 brain-dead patients as compared to control subjects (15.6⯱â¯6.9â¯ng/mL vs 17.4⯱â¯9.0â¯ng/mL; pâ¯=â¯0.383). Moderate direct correlations were observed between vitamin D and IL-8, IL-10, and IFN-γ in the prospective group of 16 brain-dead patients (IL-8: râ¯=â¯0.5, pâ¯=â¯0.049; IL-10 râ¯=â¯0.67, pâ¯=â¯0.005; IFN-γ râ¯=â¯0.6, pâ¯=â¯0.015). Vitamin D was inversely correlated with IL-6 (râ¯=â¯-0.36, pâ¯=â¯0.044) in critically ill controls. CONCLUSIONS: Vitamin D serum levels were similarly low in brain-dead and critically ill patients. In brain-dead patients, vitamin D serum levels correlated with plasma IL-8, IL-10 and IFN-γ.
Assuntos
Morte Encefálica/metabolismo , Citocinas/sangue , Inflamação/metabolismo , Vitamina D/sangue , Adulto , Catecolaminas/metabolismo , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
Experimental findings support the evidence of a persistent leucopenia triggered by brain death (BD). This study aimed to investigate leucocyte behaviour in bone marrow and blood after BD in rats. BD was induced using intracranial balloon catheter inflation. Sham-operated (SH) rats were trepanned only. Thereafter bone marrow cells were harvested every six hours from the femoral cavity and used for total and differential counts. They were analysed further by flow cytometry to characterize lymphocyte subsets, granulocyte adhesion molecules expression and apoptosis/necrosis [annexin V/propidium iodide (PI) protocol]. BD rats exhibited a reduction in bone marrow cells due to a reduction in lymphocytes (40%) and segmented cells (45%). Bone marrow lymphocyte subsets were similar in BD and SH rats (CD3, P = 0.1; CD4, P = 0.4; CD3/CD4, P = 0.4; CD5, P = 0.4, CD3/CD5, P = 0.2; CD8, P = 0.8). Expression of L-selectin and beta2 -integrins on granulocytes did not differ (CD11a, P = 0.9; CD11b/c, P = 0.7; CD62L, P = 0.1). There were no differences in the percentage of apoptosis and necrosis (Annexin V, P = 0.73; PI, P = 0.21; Annexin V/PI, P = 0.29). In conclusion, data presented suggest that the downregulation of the bone marrow is triggered by brain death itself, and it is not related to changes in lymphocyte subsets, granulocyte adhesion molecules expression or apoptosis and necrosis.
Assuntos
Células da Medula Óssea/patologia , Morte Encefálica/patologia , Animais , Apoptose , Células da Medula Óssea/imunologia , Células da Medula Óssea/metabolismo , Morte Encefálica/imunologia , Morte Encefálica/metabolismo , Moléculas de Adesão Celular/metabolismo , Modelos Animais de Doenças , Regulação para Baixo , Granulócitos/metabolismo , Hemodinâmica/fisiologia , Contagem de Leucócitos , Leucopenia/etiologia , Subpopulações de Linfócitos/imunologia , Masculino , Necrose , Ratos WistarRESUMO
BACKGROUND: Donor sex has been suggested to be a factor influencing organ transplantation outcome. Sex hormones possess inflammatory and immune-mediating properties; therefore, immune responses may differ between males and females. Brain death (BD) affects organ function by numerous mechanisms including alterations in hemodynamics, hormonal changes, and increased systemic inflammation. In this study, we investigated sex-dependent differences in the evolution of lung inflammation in a rat model of BD. MATERIALS AND METHODS: BD was induced by a sudden increase in intracranial pressure by rapidly inflating a balloon catheter inserted into the intracranial space. Groups of male, female, and ovariectomized (OVx) female rats were used. Lung vascular permeability, inducible nitric oxide synthase, and intercellular adhesion molecule 1 expression were analyzed 6 h after BD. Serum female sex hormones, vascular endothelial growth factor, and cytokine-induced neutrophil chemoattractant 1 levels were also quantified. Lung sections were analyzed by histology. RESULTS: After 6 h of BD, serum estradiol and progesterone concentrations in female rats were significantly reduced. Lung microvascular permeability was increased in females compared to males. Cytokine-induced neutrophil chemoattractant 1 and vascular endothelial growth factor concentrations were increased in female rats compared to males. Furthermore, female rats showed higher levels of leukocyte infiltration and inducible nitric oxide synthase expression in the lung parenchyma. CONCLUSIONS: Our results indicate that the more severe lung inflammation in female animals after BD might be related to acute estradiol reduction. Based on our findings, we believe that, in a future study, a group of female treated with estradiol after BD could indicate a possible therapy for the control of lung inflammation in the female donor.
Assuntos
Morte Encefálica/metabolismo , Pneumonia/metabolismo , Animais , Biomarcadores/metabolismo , Estradiol/sangue , Feminino , Pulmão/metabolismo , Pulmão/patologia , Masculino , Pneumonia/etiologia , Pneumonia/patologia , Progesterona/sangue , Ratos , Ratos Wistar , Fatores Sexuais , Obtenção de Tecidos e ÓrgãosRESUMO
BACKGROUND: Thyroid hormone treatment in brain-dead organ donors has been extensively studied and applied in the clinical setting. However, its clinical applicability remains controversial due to a varying degree of success and a lack of mechanistic understanding about the therapeutic effects of 3,3',5-Triiodo-L-thyronine (T3). T3 pre-conditioning leads to anti-apoptotic and pro-mitotic effects in liver tissue following ischemia/reperfusion injury. Therefore, we aimed to study the effects of T3 pre-conditioning in the liver of brain-dead rats. METHODS: Brain death (BD) was induced in mechanically ventilated rats by inflation of a Fogarty catheter in the epidural space. T3 (0.1 mg/kg) or vehicle was administered intraperitoneally 2 h prior to BD induction. After 4 h of BD, serum and liver tissue were collected. RT-qPCR, routine biochemistry, and immunohistochemistry were performed. RESULTS: Brain-dead animals treated with T3 had lower plasma levels of AST and ALT, reduced Bax gene expression, and less hepatic cleaved Caspase-3 activation compared to brain-dead animals treated with vehicle. Interestingly, no differences in the expression of inflammatory genes (IL-6, MCP-1, IL-1ß) or the presence of pro-mitotic markers (Cyclin-D and Ki-67) were found in brain-dead animals treated with T3 compared to vehicle-treated animals. CONCLUSION: T3 pre-conditioning leads to beneficial effects in the liver of brain-dead rats as seen by lower cellular injury and reduced apoptosis, and supports the suggested role of T3 hormone therapy in the management of brain-dead donors.
Assuntos
Apoptose/efeitos dos fármacos , Morte Encefálica/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Tri-Iodotironina/farmacologia , Animais , Morte Encefálica/metabolismo , Fígado/metabolismo , Masculino , Mitose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344RESUMO
The majority of liver grafts destined for transplantation originate from brain dead donors. However, significantly better posttransplantation outcomes are achieved when organs from living donors are used, suggesting that brain death (BD) causes irreversible damage to the liver tissue. Recently, glucagon-like peptide-1 (GLP1) analogues were shown to possess interesting hepatic protection effects in different liver disease models. We hypothesized that donor treatment with the GLP1 analogue exendin-4 (Ex-4) could alleviate BD-induced liver damage. A rat model of BD was employed in order to estimate BD-induced liver damage and Ex-4's potential protective effects. Liver damage was assessed by biochemical determination of circulating hepatic markers. Apoptosis in the hepatic tissue was assessed by immunoblot and immunohistochemistry using an antibody that only recognizes the active form of caspase-3. Gene expression changes in inflammation and stress response genes were monitored by quantitative real-time polymerase chain reaction. Here, we show that Ex-4 administration to the brain dead liver donors significantly reduces levels of circulating aspartate aminotransferase and lactate dehydrogenase. This was accompanied by a remarkable reduction in hepatocyte apoptosis. In this model, BD caused up-regulation of tumor necrosis factor and stress-related genes, confirming previous findings in clinical and animal studies. In conclusion, treatment of brain dead rats with Ex-4 reduced BD-induced liver damage. Further investigation is needed to determine the molecular basis of the observed liver protection. After testing in a randomized clinical trial, the inclusion of GLP1 analogues in organ donor management might help to improve organ quality, maximize organ donation, and possibly increase liver transplantation success rates.
Assuntos
Hepatopatias/prevenção & controle , Transplante de Fígado , Peptídeos/administração & dosagem , Peçonhas/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Morte Encefálica/metabolismo , Caspase 3/biossíntese , Caspase 3/genética , Citocinas/biossíntese , Citocinas/genética , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Exenatida , Regulação da Expressão Gênica , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Hipoglicemiantes/administração & dosagem , Immunoblotting , Imuno-Histoquímica , Fígado/efeitos dos fármacos , Fígado/patologia , Hepatopatias/genética , Hepatopatias/metabolismo , Masculino , Ratos , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: The shortage of organs is a limitation for transplantation, making the care of potential organ donors an important issue. The present systematic review and meta-analysis was carried out to assess the efficacy of interventions to stabilize hemodynamics in brain-dead donors or to improve organ function and outcomes of transplantation. METHODS: Medline, Embase, and Cochrane databases were searched. Of 5096 articles retrieved, 39 randomized controlled trials were selected. Twenty were included in a qualitative synthesis, providing data on 1277 patients. The main interventions described were desmopressin use, triiodothyronine and methylprednisolone replacement, fluid management, vasopressor therapy, mechanical ventilation strategies, and surgical techniques. RESULTS: Three meta-analyses were conducted: the first included two studies and showed that desmopressin administered to brain-dead patients was not advantageous with respect to early organ function in kidney recipients (relative risk, 0.97; 95% confidence interval [CI], 0.85-1.10; I(2) = 0%; P = 0.809). The second included four studies and showed that triiodothyronine did not add hemodynamic benefits versus standard management (weighted mean difference, 0.15; 95% CI, -0.13 to 0.42; I(2) = 17.4%; P = 0.304). The third meta-analysis (two studies) showed that ischemic liver preconditioning during harvesting procedures did not benefit survival (relative risk, 1.0; 95% CI, 0.93-1.08; I(2) = 0%; P = 0.459). CONCLUSION: The present results suggest limited efficacy of interventions focusing on the management of brain-dead donors.
Assuntos
Morte Encefálica , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos , Transplantes , Morte Encefálica/metabolismo , Morte Encefálica/fisiopatologia , Desamino Arginina Vasopressina/administração & dosagem , Hidratação , Hemodinâmica , Terapia de Reposição Hormonal , Humanos , Metilprednisolona/administração & dosagem , Respiração Artificial , Coleta de Tecidos e Órgãos/métodos , Transplantes/efeitos adversos , Tri-Iodotironina/administração & dosagem , Vasoconstritores/administração & dosagemRESUMO
The goal of this study was to evaluate if the immunohistochemical expression of alpha-3 neuronal nicotinic acetylcholine receptor subunit in sympathetic ganglia remains stable after brain death, determining the possible use of sympathetic thoracic ganglia from subjects after brain death as study group. The third left sympathetic ganglion was resected from patients divided in two groups: BD-organ donors after brain death and CON-patients submitted to sympathectomy for hyperhidrosis (control group). Immunohistochemical staining for alpha-3 neuronal nicotinic acetylcholine receptor subunit was performed; strong and weak expression areas were quantified in both groups. The BD group showed strong alpha-3 neuronal nicotinic acetylcholine receptor expression in 6.55% of the total area, whereas the CON group showed strong expression in 5.91% (p = 0.78). Weak expression was found in 6.47% of brain-dead subjects and in 7.23% of control subjects (p = 0.31). Brain death did not affect the results of the immunohistochemical analysis of sympathetic ganglia, and its use as study group is feasible.
Assuntos
Morte Encefálica/metabolismo , Gânglios Simpáticos/metabolismo , Neurônios/metabolismo , Mudanças Depois da Morte , Receptores Nicotínicos/biossíntese , Receptores Nicotínicos/genética , Acetilcolina/metabolismo , Adulto , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Receptores Nicotínicos/metabolismo , Adulto JovemRESUMO
PURPOSE: To evaluate histopathological alterations triggered by brain death and associated trauma on different solid organs in rats. METHODS: Male Wistar rats (n=37) were anesthetized with isoflurane, intubated and mechanically ventilated. A trepanation was performed and a balloon catheter inserted into intracraninal cavity and rapidly inflated with saline to induce brain death. After induction, rats were monitored for 30, 180, and 360 min for hemodynamic parameters and exsanguinated from abdominal aorta. Heart, lung, liver, and kidney were removed and fixed in paraffin to evaluation of histological alterations (H&E). Sham-operated rats were trepanned only and used as control group. RESULTS: Brain dead rats showed a hemodynamic instability with hypertensive episode in the first minute after the induction followed by hypotension for approximately 1 h. Histological analyses showed that brain death induces vascular congestion in heart (p<0.05), and lung (p<0.05); lung alveolar edema (p=0.001), kidney tubular edema (p<0.05); and leukocyte infiltration in liver (p<0.05). CONCLUSIONS: Brain death induces hemodynamic instability associated with vascular changes in solid organs and compromises most severely the lungs. However, brain death associated trauma triggers important pathophysiological alterations in these organs.(AU)
OBJETIVO: Avaliar as alterações histopatológicas desencadeadas pela morte encefálica e pelo trauma associado em diferentes órgãos sólidos em ratos. MÉTODOS: Ratos Wistar machos (n=37) foram anestesiados com isoflurano, entubados e mecanicamente ventilados. Foi realizada trepanação e um cateter foi inserido na cavidade intracraniana e insuflado rapidamente para induzir morte encefálica. Após a indução, os ratos foram monitorados por 30, 180 e 360 min para parâmetros hemodinâmicos e exsanguinados pela aorta abdominal. Coração, pulmão, fígado e rim foram removidos e fixados em parafina para avaliação de alterações histológicas (H&E). Ratos falso-operados foram apenas trepanados e usados como grupo controle. RESULTADOS: Ratos com morte encefálica apresentaram instabilidade hemodinâmica com episódio hipertensivo no primeiro minuto após a indução seguido de hipotensão por aproximadamente 1 hora. Análises histológicas demonstraram que a morte encefálica induz congestão vascular no coração (p<0,05) e pulmão (p<0,05); edema alveolar (p=0,001); edema tubular (p<0,05); e infiltrado leucocitário no fígado (p<0,05). CONCLUSÕES: A morte encefálica induz instabilidade hemodinâmica associada com mudanças vasculares em órgãos sólidos e compromete mais severamente os pulmões. Contudo, o trauma associado à morte encefálica desencadeia importantes alterações fisiopatológicas naqueles órgãos.(AU)
Assuntos
Animais , Ratos/classificação , Traumatismos Craniocerebrais , Morte Encefálica/metabolismo , Histologia/tendênciasRESUMO
BACKGROUND: Hydroxyethylstarch (HES) is a synthetic polymer of glucose that has been suggested for therapeutic use in long-term plasma expansion. The aim of this study was to test the hypothesis that the infusion of a small volume of HES may provide benefits in systemic and regional hemodynamics and metabolism in a brain-dead canine model compared with large volume crystalloid resuscitation. METHODS: Fourteen mongrel dogs were subjected to a brain-death protocol by consecutive insufflations of a balloon catheter in the epidural space. One hour after induction of brain-death, the animals were randomly assigned to two groups: NS (0.9% NaCl, 33 mL/kg), and HES (6%HES 450/0.7, 17 mL/Kg). Systemic and regional hemodynamics were evaluated using Swan-Ganz, ultrasonic flowprobes, and arterial catheters. Serial blood samples were collected for blood gas, electrolyte, and serum chemistry analysis. Systemic, hepatic, and splanchnic O(2)-derived variables were also calculated. RESULTS: Epidural balloon insufflations induced a significant increase in mean arterial pressure, cardiac output (MAP and CO, respectively), regional blood flow, and systemic vascular resistance. Following the hyperdynamic phase, severe hypotension with normalization of systemic and regional blood flow was observed. Fluid resuscitation induced a prompt increase in MAP, CO, and portal vein blood flow, and a significant reduction in systemic and pulmonary vascular resistance. There were no differences between groups in metabolic indices, liver function tests (LFTs), or renal function tests. HES was more effective than NS in restoring cardiac performance in the first 2h after fluid resuscitation (P < 0.05). Both tested solutions partially and temporarily restored systemic and regional oxygen delivery. CONCLUSION: Small volumes of 6% HES 450/0.7 improved cardiovascular performance and provided the same regional hemodynamic and metabolic benefits of large volumes of isotonic crystalloid solutions.
Assuntos
Morte Encefálica/metabolismo , Morte Encefálica/fisiopatologia , Hemodinâmica/efeitos dos fármacos , Derivados de Hidroxietil Amido/farmacologia , Substitutos do Plasma/farmacologia , Ressuscitação/métodos , Alanina Transaminase/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Débito Cardíaco/efeitos dos fármacos , Débito Cardíaco/fisiologia , Creatina Quinase/metabolismo , Cães , Glucose/metabolismo , Masculino , Modelos Animais , Fluxo Sanguíneo Regional/efeitos dos fármacos , Fluxo Sanguíneo Regional/fisiologia , Cloreto de Sódio/farmacologia , Resistência Vascular/efeitos dos fármacos , Resistência Vascular/fisiologiaRESUMO
BACKGROUND: Organs from the so-called marginal donors have been used with a significant higher risk of primary non function than organs retrieved from the optimal donors. We investigated the early metabolic changes and blood flow redistribution in splanchnic territory in an experimental model that mimics marginal brain-dead (BD) donor. MATERIAL/METHODS: Ten dogs (21.3+/-0.9 kg), were subjected to a brain death protocol induced by subdural balloon inflation and observed for 30 min thereafter without any additional interventions. Mean arterial and intracranial pressures, heart rate, cardiac output (CO), portal vein and hepatic artery blood flows (PVBF and HABF, ultrasonic flowprobe), and O(2)-derived variables were evaluated. RESULTS: An increase in arterial pressure, CO, PVBF and HABF was observed after BD induction. At the end, an intense hypotension with normalization in CO (3.0+/-0.2 vs. 2.8+/-2.8 L/min) and PVBF (687+/-114 vs. 623+/-130 ml/min) was observed, whereas HABF (277+/-33 vs. 134+/-28 ml/min, p<0.005) remained lower than baseline values. CONCLUSIONS: Despite severe hypotension induced by sudden increase of intracranial pressure, the systemic and splanchnic blood flows were partially preserved without signs of severe hypoperfusion (i.e. hyperlactatemia). Additionally, the HABF was mostly negatively affected in this model of marginal BD donor. Our data suggest that not only the cardiac output, but the intrinsic hepatic microcirculatory mechanism plays a role in the hepatic blood flow control after BD.
Assuntos
Morte Encefálica/fisiopatologia , Modelos Animais de Doenças , Oxigênio/sangue , Circulação Esplâncnica/fisiologia , Animais , Morte Encefálica/metabolismo , Débito Cardíaco/fisiologia , Cães , Hemodinâmica , Circulação Hepática/fisiologia , Microcirculação , Veia Porta/fisiopatologia , Fluxo Sanguíneo RegionalAssuntos
Humanos , Masculino , Feminino , Eutanásia , História , Morte Encefálica/diagnóstico , Morte Encefálica/metabolismo , PediatriaRESUMO
This study investigated S100beta protein as a biochemical serum marker of brain damage in severe head injury and brain death victims. Blood samples obtained from 15 patients with severe head injury admitted to the trauma intensive care unit (ICU), five patients with a diagnosis of brain death due to hemorrhage following cerebral aneurysm rupture, and five healthy individuals were investigated. The S100beta protein serum concentrations were analyzed with a immunoradiometric assay kit. The 15 patients with severe head injury were followed up for 6 months. Outcome was considered either death or recovery with ICU discharge. S100beta concentrations were closely related to brain damage. Among the severe head injury victims, higher S100beta concentrations were detected in those patients that progressed to death. The individuals with brain death had similar mean S100beta concentrations, irrespective of its cause (either trauma or vascular rupture). S100beta protein is a promising serum outcome predictor for severe head injury victims and may contribute to the early diagnosis of brain death.
Assuntos
Morte Encefálica/diagnóstico , Morte Encefálica/metabolismo , Proteínas de Ligação ao Cálcio/sangue , Traumatismos Craniocerebrais/sangue , Fatores de Crescimento Neural/sangue , Proteínas S100 , Adolescente , Adulto , Biomarcadores , Traumatismos Craniocerebrais/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Subunidade beta da Proteína Ligante de Cálcio S100RESUMO
Muerte cerebral. Mantenimiento del donante. Ablación multiorgánica. Soluciones de Preservación. Etica y transplantes. Ley 24.193 Transplante de Organos y Materiales Anátomicos
Assuntos
Morte Encefálica/diagnóstico , Doadores de Tecidos/classificação , /métodos , Respiração Artificial/métodos , Transplante/legislação & jurisprudência , Ética , Religião e Medicina , Morte , Preservação de Órgãos/normas , Preservação de Tecido/métodos , Morte Encefálica/metabolismo , Morte Encefálica/sangue , Atropina , Eletroencefalografia/métodos , Transplante/classificação , Transplante/normas , Preservação de Órgãos/instrumentação , Preservação de Tecido/história , Criopreservação/métodos , Soluções/análise , Soluções/farmacologia , Respiração Artificial/normasRESUMO
Muerte cerebral. Mantenimiento del donante. Ablación multiorgánica. Soluciones de Preservación. Etica y transplantes. Ley 24.193 Transplante de Organos y Materiales Anátomicos