A clinically relevant sheep model of orthotopic heart transplantation 24 h after donor brainstem death

BACKGROUND: Heart transplantation (HTx) from brainstem dead (BSD) donors is the gold-standard therapy for severe/end-stage cardiac disease, but is limited by a global donor heart shortage. Consequently, innovative solutions to increase donor heart availability and utilisation are rapidly expanding. Clinically relevant preclinical models are essential for evaluating interventions for human translation, yet few exist that accurately mimic all key HTx components, incorporating injuries beginning in the donor, through to the recipient. To enable future assessment of novel perfusion technologies in our research program, we thus aimed to develop a clinically relevant sheep model of HTx following 24 h of donor BSD. METHODS: BSD donors (vs. sham neurological injury, 4/group) were hemodynamically supported and monitored for 24 h, followed by heart preservation with cold static storage. Bicaval orthotopic HTx was performed in matched recipients, who were weaned from cardiopulmonary bypass (CPB), and monitored for 6 h. Donor and recipient blood were assayed for inflammatory and cardiac injury markers, and cardiac function was assessed using echocardiography. Repeated measurements between the two different groups during the study observation period were assessed by mixed ANOVA for repeated measures. RESULTS: Brainstem death caused an immediate catecholaminergic hemodynamic response (mean arterial pressure, p = 0.09), systemic inflammation (IL-6 - p = 0.025, IL-8 - p = 0.002) and cardiac injury (cardiac troponin I, p = 0.048), requiring vasopressor support (vasopressor dependency index, VDI, p = 0.023), with normalisation of biomarkers and physiology over 24 h. All hearts were weaned from CPB and monitored for 6 h post-HTx, except one (sham) recipient that died 2 h post-HTx. Hemodynamic (VDI - p = 0.592, heart rate - p = 0.747) and metabolic (blood lactate, p = 0.546) parameters post-HTx were comparable between groups, despite the observed physiological perturbations that occurred during donor BSD. All p values denote interaction among groups and time in the ANOVA for repeated measures. CONCLUSIONS: We have successfully developed an ovine HTx model following 24 h of donor BSD. After 6 h of critical care management post-HTx, there were no differences between groups, despite evident hemodynamic perturbations, systemic inflammation, and cardiac injury observed during donor BSD. This preclinical model provides a platform for critical assessment of injury development pre- and post-HTx, and novel therapeutic evaluation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40635-021-00425-4

Estudo de intervenção sobre a divisão: ilustrando as relações entre metacognição e aprendizagem

Discute-se um estudo de intervenção conduzido em um contexto experimental em que a interação adulto-criança era marcada por atividades metacognitivas com vistas a auxiliar na superação das dificuldades experimentadas por crianças com o conceito de divisão. As atividades metacognitivas propostas envolviam a tomada de consciência da criança sobre procedimentos adotados na resolução de problemas, sendo associada uma explicitação dos princípios invariantes do conceito de divisão. O estudo consistiu em um pré-teste e um pós-teste aplicado a 100 crianças de baixa renda (8 a 11 anos), alunas do 4.º ano do ensino fundamental de escolas públicas na cidade do Recife que apresentavam dificuldades com a divisão. As crianças foram distribuídas em um grupo controle e em um grupo experimental, havendo as crianças do grupo experimental participado da referida intervenção. As relações entre metacognição e aprendizagem são ilustradas a partir da apresentação e discussão de passagens extraídas das sessões de intervenção. Os resultados mostraram que no pré-teste os dois grupos não diferiam entre si, apresentando o mesmo nível de dificuldade; porém, após a intervenção, os participantes do grupo experimental superaram as dificuldades iniciais, o mesmo não sendo observado em relação aos participantes do grupo controle

The relationship between neuropsychological performance and depression in patients with traumatic brain injury

Traumatic brain injury is a multi-faceted condition that affects individuals on physical, cognitive, and emotional levels. The study investigated the relationship between depression and neuropsychological performance in a group with traumatic brain injury. A retrospective review was conducted on 75 participants who completed neuropsychological assessments. Information on clinical characteristics, sociodemographic information, neuropsychological outcomes, and Beck Depression Inventory scores were included in the analysis. Results indicated that 36% of the participants reported experiencing severe symptoms of depression, 28% moderate symptoms of depression, and 36% mild/minimal symptoms of depression. Performance on the Rey Auditory Verbal Learning Test indicated inverse relationships with depression scores suggesting that traumatic brain injury patients with lower depression scores perform better on verbal memory tasks. Similarly, findings for the written and oral versions of the Symbol Digit Modalities Test reflected inverse correlations with depression scores, indicating that lower depression scores are correlated with increased processing speed and capacity. A significant positive association between the time taken to complete the Trail Making Test Trail A and Trail B and depression scores was found, suggesting that higher depression scores in this sample were related to slower performance speed and lower executive performance. When specific clinical and sociodemographic variables were included as covariates in a partial correlational analysis, neuropsychological performance indicators and depression scores remained significant for Symbol Digit Modalities Test (oral and written), the Rey Auditory Verbal Learning Test Retrieval and Recognition trials, and Trail Making Test (Trail B). This study indicates that in a traumatic brain injury cohort, depression levels are significantly associated with specific neuropsychological performance measures. The findings of this study have implications for psychosocial treatment planning after a traumatic brain injury and contribute to our understandings of the inter-relationship between cognition and emotion.http://sap.sagepub.comhj2017Psycholog

An Ovine Model of Hemorrhagic Shock and Resuscitation, to Assess Recovery of Tissue Oxygen Delivery and Oxygen Debt, and Inform Patient Blood Management.

BACKGROUND: Aggressive fluid or blood component transfusion for severe hemorrhagic shock may restore macrocirculatory parameters, but not always improve microcirculatory perfusion and tissue oxygen delivery. We established an ovine model of hemorrhagic shock to systematically assess tissue oxygen delivery and repayment of oxygen debt; appropriate outcomes to guide Patient Blood Management. METHODS: Female Dorset-cross sheep were anesthetized, intubated, and subjected to comprehensive macrohemodynamic, regional tissue oxygen saturation (StO2), sublingual capillary imaging, and arterial lactate monitoring confirmed by invasive organ-specific microvascular perfusion, oxygen pressure, and lactate/pyruvate levels in brain, kidney, liver, and skeletal muscle. Shock was induced by stepwise withdrawal of venous blood until MAP was 30 mm Hg, mixed venous oxygen saturation (SvO2) 4 mM. Resuscitation with PlasmaLyte® was dosed to achieve MAP > 65 mm Hg. RESULTS: Hemorrhage impacted primary outcomes between baseline and development of shock: MAP 89 ± 5 to 31 ± 5 mm Hg (P < 0.01), SvO2 70 ± 7 to 23 ± 8% (P < 0.05), cerebral regional tissue StO2 77 ± 11 to 65 ± 9% (P < 0.01), peripheral muscle StO2 66 ± 8 to 16 ± 9% (P < 0.01), arterial lactate 1.5 ± 1.0 to 5.1 ± 0.8 mM (P < 0.01), and base excess 1.1 ± 2.2 to -3.6 ± 1.7 mM (P < 0.05). Invasive organ-specific monitoring confirmed reduced tissue oxygen delivery; oxygen tension decreased and lactate increased in all tissues, but moderately in brain. Blood volume replacement with PlasmaLyte® improved primary outcome measures toward baseline, confirmed by organ-specific measures, despite hemoglobin reduced from baseline 10.8 ± 1.2 to 5.9 ± 1.1 g/dL post-resuscitation (P < 0.01). CONCLUSION: Non-invasive measures of tissue oxygen delivery and oxygen debt repayment are suitable outcomes to inform Patient Blood Management of hemorrhagic shock, translatable for pre-clinical assessment of novel resuscitation strategies