OBJECTIVES: To evaluate the effects of sympathectomy on the myocardium in an experimental model. METHODS: The study evaluated three groups of male Wistar rats: control (CT; n=15), left unilateral sympathectomy (UNI; n=15), and bilateral sympathectomy (BIL; n=31). Sympathectomy was performed by injection of absolute alcohol into the space of the spinous process of the C7 vertebra. After 6 weeks, we assessed the chronotropic properties at rest and stress, cardiovascular autonomic modulation, myocardial and peripheral catecholamines, and beta-adrenergic receptors in the myocardium. The treadmill test consisted of an escalated protocol with a velocity increment until the maximal velocity tolerated by the animal was reached. RESULTS: The bilateral group had higher levels of peripheral catecholamines, and consequently, a higher heart rate (HR) and blood pressure levels. This suggests that the activation of a compensatory pathway in this group may have deleterious effects. The BIL group had basal tachycardia immediately before the exercise test and increased tachycardia at peak exercise (p<0.01); the blood pressure had the same pattern (p=0.0365). The variables related to autonomic modulation were not significantly different between groups, with the exception of the high frequency (HF) variable, which showed significant differences in CT vs UNI. There was no significant difference in beta receptor expression between groups. There was a higher concentration of peripheral norepinephrine in the BIL group (p=0.0001), and no significant difference in myocardial norepinephrine (p=0.09). CONCLUSION: These findings suggest that an extra cardiac compensatory pathway increases the sympathetic tonus and maintains a higher HR and higher levels of peripheral catecholamines in the procedure groups. The increase in HF activity can be interpreted as an attempt to increase the parasympathetic tonus to balance the greater sympathetic activity.

Surgical neuromodulation therapies are still considered a last resort when standard therapies have failed for patients with progressive heart failure (HF). Although a number of experimental studies have provided robust evidence of its effectiveness, the lack of strong clinical evidence discourages practitioners. Thoracic unilateral sympathectomy has been extensively studied and has failed to show significant clinical improvement in HF patients. Most recently, bilateral sympathectomy effect was associated with a high degree of success in HF models, opening the perspective to be investigated in randomized controlled clinical trials. In addition, a series of clinical trials showed that bilateral sympathectomy was associated with a decreased risk of sudden death, which is an important outcome in patients with HF. These aspects indicates that bilateral sympathectomy could be an important alternative in the treatment of HF wherein pharmacological treatment barely reaches the target dose.

RESUMO Objetivo A morte cerebral (MC) desencadeia alterações hemodinâmicas e inflamatórias importantes, comprometendo a viabilidade dos órgãos empregados em transplantes. Para compreender melhor as alterações microcirculatórias nos pulmões de doadores com MC, o presente estudo investigou a microcirculação pulmonar em um modelo de roedor com MC via microscopia intravital. Métodos Ratos Wistar machos foram anestesiados e ventilados mecanicamente. Eles foram submetidos a trepanação e a MC induzida por meio do aumento da pressão intracraniana. Os ratos do grupo Sham (SH), utilizado como controle, foram submetidos apenas à trepanação. Em ambos os grupos, foram monitorados o O2 expiratório e o CO2, e, após 3 horas, foi realizada a toracotomia e criada uma janela para observar a superfície pulmonar usando o sistema de microscopia intravital. As expressões pulmonares das moléculas de adesão intercelular (ICAM)-1 e da óxido nítrico-sintase endotelial (eNOS) foram avaliadas por imuno-histoquímica, e as citocinas foram medidas em amostras pulmonares. Resultados Três horas após os procedimentos cirúrgicos, a perfusão pulmonar foi de 73% no grupo SH. Por outro lado, os animais com MC apresentaram uma importante diminuição na perfusão do órgão para 28% (p = 0,036). O comprometimento microcirculatório pulmonar após a indução de MC foi associado a um aumento do número de leucócitos recrutados para o tecido pulmonar, além de uma redução na expressão de eNOS e um aumento na expressão de ICAM-1 nas células endoteliais do pulmão. Os ratos com MC apresentaram valores mais elevados de O2 expiratório e valores mais baixos de CO2 em comparação com os animais SH após 3 horas de monitorização. Conclusões Os dados apresentados demonstraram que a MC desencadeia uma importante hipoperfusão e inflamação nos pulmões, comprometendo a microcirculação pulmonar do doador.

ABSTRACT Objective Brain death (BD) triggers important hemodynamic and inflammatory alterations, compromising the viability of organs suitable for transplantation. To better understand the microcirculatory alterations in donor lungs caused by BD. The present study investigated the pulmonary microcirculation in a rodent model of BD via intravital microscopy. Methods Male Wistar rats were anaesthetized and mechanically ventilated. They were trepanned and BD was induced through the increase in intracranial pressure. As control group, sham-operated (SH) rats were trepanned only. In both groups, expiratory O2 and CO2 were monitored and after three hours, a thoracotomy was performed, and a window was created to observe the lung surface using an epi-fluorescence intravital microscopy. Lung expression of intercellular adhesion molecule (ICAM)-1 and endothelial nitric oxide synthase (eNOS) was evaluated by immunohistochemistry, and cytokines were measured in lung samples. Results Three hours after the surgical procedures, pulmonary perfusion was 73% in the SH group. On the other hand, BD animals showed an important decrease in organ perfusion to 28% (p = 0.036). Lung microcirculatory compromise after BD induction was associated with an augmentation of the number of leukocytes recruited to lung tissue, and with a reduction in eNOS expression and an increase in ICAM-1 expression on lung endothelial cells. BD rats showed higher values of expiratory O2 and lower values of CO2 in comparison with SH animals after three hours of monitoring. Conclusion Data presented showed that BD triggers an important hypoperfusion and inflammation in the lungs, compromising the donor pulmonary microcirculation.

ABSTRACT Pavement design, initially based on empirical methods, has been improved and, currently, there is a tendency to replace these methods by mechanistic-empirical ones. This new methodology uses detailed information on traffic, climate and pavement structure to obtain accurate performance predictions, providing a better design. In this study, it was performed a sensitivity analysis of flexible pavements to investigate the effect that the variation of annual average daily traffic (AADT) and traffic growth rate has on structural pavement responses. Therefore, simulations were done using two computer programs, MEPDG and AASHTOWare Pavement ME Design, whose results indicated that the pavement has sensitivity to both variations that were studied (AADT and traffic growth rate), demonstrating higher deterioration values when the traffic growth rate was nonlinear. It was also concluded that the difference between sensitivity values obtained by both programs was insignificant.

RESUMEN El diseño del pavimento, inicialmente basado en métodos empíricos, ha sido mejorado y, actualmente hay una tendencia a sustituir estos métodos por métodos empírico-mecánicos. Esta nueva metodología utiliza la información detallada del tráfico, del clima y de la estructura del pavimento para obtener predicciones precisas de desempeño, proporcionando un mejor diseño. En este trabajo, se realizó un análisis de sensibilidad de los pavimentos flexibles para investigar el efecto que tiene la variación del tránsito promedio diario anual (TPDA) y la tasa de crecimiento del tráfico en las respuestas estructurales al pavimento. Por lo tanto, las simulaciones se realizaron mediante dos programas de ordenador, el programa MEPDG y el AASHTOWare Pavement ME Design, cuyos resultados indicaron que el pavimento tiene sensibilidad a ambas variaciones estudiadas (TPDA y tasa de crecimiento del tráfico), demostrando mayores valores de deterioro cuando la tasa de crecimiento del tráfico fue no lineal. También se concluyó que la diferencia entre los valores de sensibilidad obtenidos por los dos programas era insignificante.

OBJECTIVES: Brain death is typically followed by autonomic changes that lead to hemodynamic instability, which is likely associated with microcirculatory dysfunction and inflammation. We evaluated the role of the microcirculation in the hemodynamic and inflammatory events that occur after brain death and the effects of autonomic storm inhibition via thoracic epidural blockade on mesenteric microcirculatory changes and inflammatory responses. METHODS: Male Wistar rats were anesthetized and mechanically ventilated. Brain death was induced via intracranial balloon inflation. Bupivacaine (brain death-thoracic epidural blockade group) or saline (brain death group) infusion via an epidural catheter was initiated immediately before brain death induction. Sham-operated animals were used as controls (SH group). The mesenteric microcirculation was analyzed via intravital microscopy, and the expression of adhesion molecules was evaluated via immunohistochemistry 180 min after brain death induction. RESULTS: A significant difference in mean arterial pressure behavior was observed between the brain death-thoracic epidural blockade group and the other groups, indicating that the former group experienced autonomic storm inhibition. However, the proportion of perfused small vessels in the brain death-thoracic epidural blockade group was similar to or lower than that in the brain death and SH groups, respectively. The expression of intercellular adhesion molecule 1 was similar between the brain death-thoracic epidural blockade and brain death groups but was significantly lower in the SH group than in the other two groups. The number of migrating leukocytes in the perivascular tissue followed the same trend for all groups. CONCLUSIONS: Although thoracic epidural blockade effectively inhibited the autonomic storm, it did not affect mesenteric hypoperfusion or inflammation induced by brain death.

OBJECTIVE: Experimental findings support clinical evidence that brain death impairs the viability of organs for transplantation, triggering hemodynamic, hormonal, and inflammatory responses. However, several of these events could be consequences of brain death-associated trauma. This study investigated microcirculatory alterations and systemic inflammatory markers in brain-dead rats and the influence of the associated trauma. METHOD: Brain death was induced using intracranial balloon inflation; sham-operated rats were trepanned only. After 30 or 180 min, the mesenteric microcirculation was observed using intravital microscopy. The expression of Pselectin and ICAM-1 on the endothelium was evaluated using immunohistochemistry. The serum cytokine, chemokine, and corticosterone levels were quantified using enzyme-linked immunosorbent assays. White blood cell counts were also determined. RESULTS: Brain death resulted in a decrease in the mesenteric perfusion to 30%, a 2.6-fold increase in the expression of ICAM-1 and leukocyte migration at the mesentery, a 70% reduction in the serum corticosterone level and pronounced leukopenia. Similar increases in the cytokine and chemokine levels were seen in the both the experimental and control animals. CONCLUSION: The data presented in this study suggest that brain death itself induces hypoperfusion in the mesenteric microcirculation that is associated with a pronounced reduction in the endogenous corticosterone level, thereby leading to increased local inflammation and organ dysfunction. These events are paradoxically associated with induced leukopenia after brain damage

PRUPOSE: Bacterial translocation has been shown to occur in critically ill patients after extensive trauma, shock, sepsis, or thermal injury. The present study investigates mesenteric microcirculatory dysfunctions, the bacterial translocation phenomenon, and hemodynamic/metabolic disturbances in a rat model of intestinal obstruction and ischemia. METHODS: Anesthetized (pentobarbital 50 mg/kg, i.p.) male Wistar rats (250-350 g) were submitted to intestinal obstruction or laparotomy without intestinal obstruction (Sham) and were evaluated 24 hours later. Bacterial translocation was assessed by bacterial culture of the mesenteric lymph nodes (MLN), liver, spleen, and blood. Leukocyte-endothelial interactions in the mesenteric microcirculation were assessed by intravital microscopy, and P-selectin and intercellular adhesion molecule (ICAM)-1 expressions were quantified by immunohistochemistry. Hematocrit, blood gases, lactate, glucose, white blood cells, serum urea, creatinine, bilirubin, and hepatic enzymes were measured. RESULTS: About 86% of intestinal obstruction rats presented positive cultures for E. coli in samples of the mesenteric lymph nodes, liver, and spleen, and 57% had positive hemocultures. In comparison to the Sham rats, intestinal obstruction induced neutrophilia and increased the number of rolling (~2-fold), adherent (~5-fold), and migrated leukocytes (~11-fold); this increase was accompanied by an increased expression of P-selectin (~2-fold) and intercellular adhesion molecule-1 (~2-fold) in the mesenteric microcirculation. Intestinal obstruction rats exhibited decreased PaCO2, alkalosis, hyperlactatemia, and hyperglycemia, and increased blood potassium, hepatic enzyme activity, serum urea, creatinine, and bilirubin. A high mortality rate was observed after intestinal obstruction (83% at 72 h vs. 0% in Sham rats). CONCLUSION: Intestinal obstruction and ischemia in rats is a relevant model for the in vivo study of mesenteric microcirculatory dysfunction and the occurrence of bacterial translocation. This model parallels the events implicated in multiple organ dysfunction (MOD) and death.