Intracranial hypertension (IH) develops in approximately 50% of all patients with severe traumatic brain injury (TBI) and is more common in patients with intracranial hematoma (ICH) 1,2 . Therefore, it is very important to identify a suitable animal model to study and understand the pathophysiology of refractory IH to develop effective treatments.Many models of neurosurgical experiments in small animals, such as rats and cats, have been developed; however, compared to humans, they have smaller brain volumes and more distinct behaviors 3,4 . While there are existing porcine models, they simulate ICH by infusing autologous blood into the brain tissue and do not replicate intracranial lesions [3][4][5][6] . ABSTRACTObjective: Intracranial hypertension (IH) develops in approximately 50% of all patients with severe traumatic brain injury (TBI). Therefore, it is very important to identify a suitable animal model to study and understand the pathophysiology of refractory IH to develop effective treatments. Methods: We describe a new experimental porcine model designed to simulate expansive brain hematoma causing IH. Under anesthesia, IH was simulated with a balloon insufflation. The IH variables were measured with intracranial pressure (ICP) parenchymal monitoring, epidural, cerebral oximetry, and transcranial Doppler (TCD). Results: None of the animals died during the experiment. The ICP epidural showed a slower rise compared with parenchymal ICP. We found a correlation between ICP and cerebral oximetry. Conclusion: The model described here seems useful to understand some of the pathophysiological characteristics of acute IH. Keywords: experimental model, intracranial hypertension, transcranial doppler sonography. RESUMOObjetivo: A hipertensão intracraniana (HIC) ocorre em até 50% de todos os pacientes com traumatismo cranioencefálico (TCE). Por isso, é importante estabelecer um modelo animal adequado para estudar a fisiopatologia da HIC refratária, com a perspectiva de desenvolver tratamentos eficazes. Métodos: Os animais foram submetidos a um protocolo padrão de anestesia. A hipertensão intracraniana foi estabelecida através de insuflação de um balão. As variáveis HIC foram medidas com a pressão intracraniana (PIC) do parênquima, oximetria, epidural e doppler transcraniano. Resultados: A PIC epidural apresentou elevação mais lenta, comparada com a PIC parenquimal. Houve correlação entre a PIC e a oximetria cerebral. O registro da PIC, oximetria e índice de pulsatilidade foi realizado em todos os animais sem dificuldade. Conclusão: O modelo descrito parece ser útil para a compreensão de algumas características fisiopatológicas na HIC aguda.Palavras-chave: pressão intracraniana, ultrassonografia, doppler transcraniana, modelos experimentais.
OBJECTIVE:In most cases of pediatric liver transplantation, the clinical scenario of large-for-size transplants can lead to hepatic dysfunction and a decreased blood supply to the liver graft. The objective of the present experimental investigation was to evaluate the effects of ischemic preconditioning on this clinical entity.METHODS:Eighteen pigs were divided into three groups and underwent liver transplantation: a control group, in which the weights of the donors were similar to those of the recipients, a large-for-size group, and a large-for-size + ischemic preconditioning group. Blood samples were collected from the recipients to evaluate the pH and the sodium, potassium, aspartate aminotransferase and alanine aminotransferase levels. In addition, hepatic tissue was sampled from the recipients for histological evaluation, immunohistochemical analyses to detect hepatocyte apoptosis and proliferation and molecular analyses to evaluate the gene expression of Bax (pro-apoptotic), Bcl-XL (anti-apoptotic), c-Fos and c-Jun (immediate-early genes), ischemia-reperfusion-related inflammatory cytokines (IL-1, TNF-alpha and IL-6, which is also a stimulator of hepatocyte regeneration), intracellular adhesion molecule, endothelial nitric oxide synthase (a mediator of the protective effect of ischemic preconditioning) and TGF-beta (a pro-fibrogenic cytokine).RESULTS:All animals developed acidosis. At 1 hour and 3 hours after reperfusion, the animals in the large-for-size and large-for-size + ischemic preconditioning groups had decreased serum levels of Na and increased serum levels of K and aspartate aminotransferase compared with the control group. The molecular analysis revealed higher expression of the Bax, TNF-alpha, I-CAM and TGF-beta genes in the large-for-size group compared with the control and large-for-size + ischemic preconditioning groups. Ischemic preconditioning was responsible for an increase in c-Fos, IL-1, IL-6 and e-NOS gene expression.CONCLUSION:Ischemia-reperfusion injury in this model of large-for-size liver transplantation could be partially attenuated by ischemic preconditioning.
PURPOSE:To evaluate intestinal inflammatory and apoptotic processes after intestinal ischemia/reperfusion injury, modulated by pentoxifylline and hypertonic saline. METHODS:It was allocated into four groups (n=6), 24 male Wistar rats (200 to 250g) and submitted to intestinal ischemia for 40 min and reperfusion for 80 min: IR (did not receive any treatment); HS group (Hypertonic Saline, 4ml/kg-IV); PTX group (Pentoxifylline, 30mg/ kg-IV); HS+PTX group (Hypertonic Saline and Pentoxifylline). All animals were heparinized (100U/kg). At the end of reperfusion, ileal fragments were removed and stained on hematoxylin-eosin and histochemical studies for COX-2, Bcl-2 and cleaved caspase-3. RESULTS:The values of sO 2 were higher on treated groups at 40 minutes of reperfusion (p=0.0081) and 80 minutes of reperfusion (p=0.0072). Serum lactate values were lower on treated groups after 40 minutes of reperfusion (p=0.0003) and 80 minutes of reperfusion (p=0.0098). Morphologic tissue injuries showed higher grades on IR group versus other groups: HS (p=0.0006), PTX (p=0.0433) and HS+PTX (p=0.0040). The histochemical study showed lesser expression of COX-2 (p=0.0015) and Bcl-2 (p=0.0012) on HS+PTX group. A lower expression of cleaved caspase-3 was demonstrated in PTX (p=0.0090; PTXvsIR). CONCLUSION:The combined use of pentoxifylline and hypertonic saline offers best results on inflammatory and apoptotic inhibitory aspects after intestinal ischemia/reperfusion.
OBJECTIVE:To evaluate the feasibility of using endovascular repair to treat penetrating arterial injuries with covered stents. Feasibility was examined according to the circumferential extent of the injury.INTRODUCTION:Surgical trauma often increases the risk of major morbidity and mortality associated with vascular injury, and endovascular repair has many advantages in such situations.METHODS:Twenty white male domestic pigs weighing 28-38 kg with controlled vascular injuries were divided into four equal groups according to the circumferential extent of their vascular lesion (i.e., no lesion, lesion <50%, lesion >50%, and complete lesion). The left common carotid artery was dissected with proximal and distal control, and this procedure was followed by controlled sectioning of the arterial wall. Local manual compression was applied for 10 min and was followed by endovascular repair with the placement of a 5×50 mm VIABHANTM covered stent using the femoral approach. We also monitored additional variables, such as the duration of the procedures (the mean was 56.3±19.1 min), ultrasound parameters (e.g., maximum arterial diameter, peak systolic and diastolic velocity, and resistance index), arteriography findings, and fluctuations in vital signs (e.g., cardiac output, arterial pressure, and central venous pressure).RESULTS:The experimental procedure was found to be feasible and reproducible. Repairs were successful in all animals in the control (no lesion) and <50% lesion groups. Success was also achieved in four out of five pigs in the >50% group and in one pig in the complete lesion group.DISCUSSION:The endovascular repair of an arterial injury is possible, but success depends on the circumferential extent of the arterial lesion. The present experimental model, which involved endovascular techniques, highlighted important factors that must be considered in future studies involving similar animals and materials.
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