Abstract Objective: To evaluate acute and chronic changes seen on angiographic and histopathological studies of porcine rete mirabile, comparing those treated with the Menox liquid embolic system (LES) and those treated with the Onyx LES. Materials and Methods: Five pigs, each weighing approximately 35 kg, were submitted to rete mirabile embolization under general anesthesia and fluoroscopic guidance, with the Menox LES or Onyx LES. Four animals were treated with the Menox LES and underwent cerebral angiography, followed by euthanasia, at 1, 30, 60, and 90 days after embolization. One animal was treated with the Onyx LES underwent the same procedures at 30 days after embolization. In a subsequent histopathological analysis, we compared the Menox LES and Onyx LES in terms of the acute and chronic changes observed. Results: We observed no significant changes in blood pressure, heart rate, or electrocardiographic parameters that could be attributed to the super-selective infusion of dimethyl sulfoxide or the Menox embolic agent. Fluoroscopy showed adequate material opacity, appropriate progression to the center of the rete mirabile and complete unilateral embolization. Microcatheters were uneventfully detached from the embolized nidus. We observed mild to moderate intravascular and extravascular inflammatory responses, without histological evidence of necrotizing arteritis. There were no adverse neurovascular events. Conclusion: The Menox LES appears to be safe and effective, as well as being apparently equivalent to the Onyx LES in terms of the postprocedure angiographic and histopathological findings.

Resumo Objetivo: Avaliar as alterações angiográficas e histopatológicas agudas e crônicas em rete mirabile suína tratadas com o Menox liquid embolic system (LES) e comparar essas alterações com a embolização com Onyx LES. Materiais e Métodos: A embolização da rete mirabile com Menox LES e Onyx LES foi realizada em cinco suínos pesando cerca de 35 kg sob anestesia geral e orientação fluoroscópica. Quatro animais tratados com Menox LES foram submetidos a angiografia cerebral seguida de eutanásia após 1, 30, 60 e 90 dias e um animal tratado com Onix LES foi submetido ao mesmo procedimento após 30 dias. A análise histopatológica subsequente para alterações agudas e crônicas avaliou o desempenho do Menox LES comparado ao Onyx LES. Resultados: Não foram observadas alterações significativas atribuíveis à infusão superseletiva de dimetilsulfóxido ou Menox nos parâmetros de pressão arterial, frequência cardíaca ou eletrocardiograma. A fluoroscopia mostrou opacidade adequada do material, progressão adequada para o centro da rete mirabile e embolização unilateral completa. Os microcateteres foram retirados do nidus embolizado sem complicações. Observou-se resposta inflamatória intravascular e extravascular leve a moderada, sem indício histológico de arterite necrosante. Nenhum dos casos apresentou eventos neurovasculares adversos. Conclusão: A injeção de Menox LES mostrou-se segura e eficaz, além de ser equivalente ao Onyx LES em relação aos achados angiográficos e histopatológicos pós-procedimento.

RESUMO Antecedentes: O Doppler transcraniano (DTC) é uma técnica não invasiva para a avaliação da hemodinâmica cerebral, porém existem controvérsias na literatura sobre sua aplicabilidade preditiva em situações de elevada pressão intracraniana (PIC). Objetivo: Investigar o fluxo sanguíneo cerebral pelo DTC e correlacioná-lo com as variações da PIC na fase aguda da hipertensão intracraniana em modelo animal. Métodos: Dois grupos de animais (suínos) foram submetidos a hipertensão intracraniana secundária à indução de diferentes volumes de hematoma, por meio da insuflação de balão intracraniano controlado com 4 e 7 mL de solução salina fisiológica (grupos A e B, respectivamente). Em seguida, administrou-se infusão venosa de solução salina hipertônica (SSH 3%). Foram coletados os valores dos parâmetros de PIC e DTC (velocidade sistólica [FVs], diastólica [FVd] e média [FVm] do fluxo sanguíneo cerebral), bem como o índice de pulsatilidade (IP). Comparações entre os parâmetros do DTC e o monitoramento da PIC foram realizadas. Resultados: Vinte porcos foram estudados, dez no grupo A e dez no grupo B. Correlação significativa entre IP e PIC foi obtida, principalmente logo após a elevação abrupta da PIC. Não houve correlação entre PIC e FVs, FVd ou FVm separadamente. Também não houve alteração significativa na PIC após a infusão de SSH. Conclusões: Esses resultados demonstram o potencial do IP como um bom parâmetro para a avaliação de pacientes com suspeita de elevação da PIC.

ABSTRACT Background: Transcranial Doppler has been tested in the evaluation of cerebral hemodynamics as a non-invasive assessment of intracranial pressure (ICP), but there is controversy in the literature about its actual benefit and usefulness in this situation. Objective: To investigate cerebral blood flow assessed by Doppler technique and correlate with the variations of the ICP in the acute phase of intracranial hypertension in an animal model. Methods: An experimental animal model of intracranial hypertension was used. The experiment consisted of two groups of animals in which intracranial balloons were implanted and inflated with 4 mL (A) and 7 mL (B) for controlled simulation of different volumes of hematoma. The values of ICP and Doppler parameters (systolic [FVs], diastolic [FVd], and mean [FVm] cerebral blood flow velocities and pulsatility index [PI]) were collected during the entire procedure (before and during hematoma simulations and venous hypertonic saline infusion intervention). Comparisons between Doppler parameters and ICP monitoring were performed. Results: Twenty pigs were studied, 10 in group A and 10 in group B. A significant correlation between PI and ICP was obtained, especially shortly after abrupt elevation of ICP. There was no correlation between ICP and FVs, FVd or FVm separately. There was also no significant change in ICP after intravenous infusion of hypertonic saline solution. Conclusions: These results demonstrate the potential of PI as a parameter for the evaluation of patients with suspected ICP elevation.

ABSTRACT Purpose: To determine the normal optical nerve sheath (ONS) diameter ultrasonography (ONSUS) and evaluate the possible effects of drugs on ONS diameter during anesthetic induction in healthy pigs. Methods: Healthy piglets were divided into three groups: a control group, that received xylazine and ketamine (X/K); other that received xylazine, ketamine and propofol (X/K/P); and a third group that received xylazine, ketamine, and thiopental (X/K/T). The sheath diameter was assessed by ultrasonography calculating the average of three measurements of each eye from the left and right sides. Results: 118 animals were anesthetized (49 X/K 33 X/K/P and 39 X/K/T). Mean ONS sizes on both sides in each group were 0.394 ± 0.048 (X/K), 0.407 ± 0.029 (X/K/P) and 0.378 ± 0.042 cm (X/K/T) (medians of 0.400, 0.405 and 0.389, respectively). The ONS diameter varied from 0.287–0.512 cm (mean of 0.302 ± 0.039 cm). For group X/K, the mean diameter was 0.394 ± 0.048 cm. Significant differences in ONS sizes between the groups P and T (X/K/P > X/K/T, p = 0.003) were found. No statistically significant differences were detected when other groups were compared (X/K = X/K/P, p = 0.302; X/K = X/K/T, p = 0.294). Conclusions: Sedation with thiopental lead to significative ONS diameter reduction in comparison with propofol. ONSUS may be useful to evaluate responses to thiopental administration.

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 sO2were 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.

Objetivo 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.

Objective 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.

OBJECTIVE: The ideal ratio between liver graft mass and recipient body weight for liver transplantation in small infants is unknown; however, if this ratio is over 4%, a condition called large-for-size may occur. Experimental models of large-for-size liver transplants have not been described in the literature. In addition, orthotopic liver transplantation is marked by high morbidity and mortality rates in animals due to the clamping of the venous splanchnic system. Therefore, the objective of this study was to create a porcine model of large-for-size liver transplantation with clamping of the supraceliac aorta during the anhepatic phase as an alternative to venovenous bypass. METHOD: Fourteen pigs underwent liver transplantation with whole-liver grafts without venovenous bypass and were divided into two experimental groups: the control group, in which the weights of the donors were similar to the weights of the recipients; and the large-for-size group, in which the weights of the donors were nearly 2 times the weights of the recipients. Hemodynamic data, the results of serum biochemical analyses and histological examination of the transplanted livers were collected. RESULTS: The mortality rate in both groups was 16.5% (1/7). The animals in the large-for-size group had increased serum levels of potassium, sodium, aspartate aminotransferase and alanine aminotransferase after graft reperfusion. The histological analyses revealed that there were no significant differences between the groups. CONCLUSION: This transplant method is a feasible experimental model of large-for-size liver transplantation.

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 5x50 mm VIABHAN TM 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.