A Vancomicina (VCM) é indicada no combate à infecções por Gram-positivas, porém não é considerada um agente de primeira escolha por causa dos seus efeitos adversos. Acredita-se que o estresse oxidativo é o principal mecanismo responsável pela lesão endotelial e consequente toxicidade da VCM, que varia desde flebites à nefrotoxicidade. Ademais, as recomendações de doses, diluições, taxas e tipos de infusão ainda são controversos. O objetivo deste trabalho foi determinar o efeito de diferentes diluições de VCM na lesão endotelial, hepática e renal utilizando parâmetros bioquímicos e análise histopatológica. Ratos Wistar foram divididos aleatoriamente em seis grupos e submetidos à canulação da veia femoral para a administração de medicamentos. Os grupos controle receberam 0,9 ml de salina e os outros receberam VCM (10mg/Kg/dia) nas diluições de 5.0 e 10.0 mg/ml durante 3 e 7 dias. Homocisteína, PCR-us, AST, ALT, GGT, ureia, creatinina, licopeno, alfa-tocoferol, beta-caroteno e retinol foram analisados. Fragmentos de rins, fígado e veia femoral canulada foram coletados. Este estudo mostrou alterações na ALT, caracterizando hepatotoxicidade. Entretanto, as diluições dos medicamentos não foram capazes de evidenciar alterações nos outros parâmetros bioquímicos. Por outro lado, alterações histopatológicas foram observadas nos rins e endotélio. Mais estudos são necessários para a caracterização do efeito da VCM quanto à toxicidade nos rins e endotélio e ainda na busca de marcadores bioquímicos capazes de evidenciar tais alterações morfológicas.

Vancomycin (VCM) is indicated in combat against Gram-positive infections, but it is not considered a first-choice drug because of its adverse effects. It is believed that oxidative stress is the primary mechanism of endothelial injury and the consequent VCM toxicity, which varies from phlebitis to nephrotoxicity. Moreover, dose recommendations, dilution, rates and types of infusion are still controversial. The aim of this study was to determine the effect of different VCM dilutions in endothelial, liver and kidney injuries by biochemical parameters and histopathological analysis. Wistar rats were randomly divided into six groups and subjected to femoral vein cannulation for drug administration. Control groups received 0.9 ml of saline and the others received VCM (10mg/Kg/day) at dilutions of 5.0 and 10.0 mg/mL for 3 and 7 days. Homocysteine, hs-CRP, AST, ALT, GGT, urea, creatinine, lycopene, alpha-tocopherol, beta-carotene and retinol were analyzed. Kidney, liver and cannulated femoral vein fragments were collected.This study showed alterations in ALT which featured hepatotoxicity. However, drug dilutions were not able to show changes in other biochemical parameters. In contrast, kidney and endothelium pathological changes were observed. More studies are needed to characterize VCM induced kidney and endothelium toxicity and biochemical markers able to show such morphological modifications.

OBJECTIVE: Previous studies have demonstrated a relationship between brain oxidative stress and cardiovascular regulation. We evaluated the effects of central catalase inhibition on cardiovascular responses in spontaneously hypertensive rats exposed to sidestream cigarette smoke. METHODS: Male Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SH) (16 weeks old) were implanted with a stainless steel guide cannula leading into the fourth cerebral ventricle (4th V). The femoral artery and vein were cannulated for arterial pressure and heart rate measurement and drug infusion, respectively. The rats were exposed to sidestream cigarette smoke for 180 minutes/day, 5 days/week for 3 weeks (CO: 100-300 ppm). The baroreflex was tested using a pressor dose of phenylephrine (8 μg/kg, bolus) and a depressor dose of sodium nitroprusside (50 μg/kg, bolus). Cardiovascular responses were evaluated before and 5, 15, 30 and 60 minutes after injection of a catalase inhibitor (3-amino-1,2,4-triazole, 0.001 g/100 μL) into the 4th V. RESULTS: Vehicle administration into the 4th V did not affect the cardiovascular response, whereas administration of the central catalase inhibitor increased the basal HR and attenuated the bradycardic peak (p<0.05) to a greater extent in WKY rats exposed to sidestream cigarette smoke than in WKY rats exposed to fresh air. However, in spontaneously hypertensive rats, the effect of the catalase inhibitor treatment was stronger in the fresh air condition (p<0.05). CONCLUSION: Administration of a catalase inhibitor into the 4th V combined with exposure to sidestream cigarette smoke has a stronger effect in WKY rats than in SH rats.

OBJECTIVE: This study aimed to investigate whether previous exercise training could prevent or attenuate acute cardiac alterations after myocardial infarction. METHODS: Female rats were submitted to swim training (1 h/day; 5 days/week) or allowed to remain sedentary for 8 weeks. Afterwards, they were randomly assigned to left coronary artery occlusion or sham surgery. After this procedure, the rats remained sedentary for one week until euthanasia. Cardiac structural and functional analyses were performed using Doppler echocardiography. The rats that had a moderate or large infarct size were included in the evaluations. The data (mean + SEM) were analyzed using a two-way ANOVA model followed byTukey's post-hoc test. RESULTS: After the surgery, no significant difference between the exercise and sedentary groups was observed in the left ventricular infarct sizes (34.58 + 3.04 vs. 37.59 + 3.07). In another group of rats evaluated with Evans blue 1 h after myocardial infarction, no siginificant difference in the area at risk was observed between the exercised and sedentary rats (49.73 + 1.52 vs. 45.48 + 3.49). The changes in the left ventricular fractional areas for the exercised and sedentary myocardial infarction groups (36 + 2% and 39 + 3%, respectively) were smaller than those for the exercise sham surgery (ES, 67+1%) and sedentary sham surgery (SS, 69 + 2%) groups. The E/A was higher in the sedentary myocardial infarction (4.4 + 0.3) and exercised myocardial infarction (5.5 + 0.3) rats than in the SS (2.4 + 0.1) and ES (2.2 + 0.1) rats. CONCLUSION: Previous swim training of female rats does not attenuate systolic and diastolic function alterations after myocardial infarction induced by left coronary artery occlusion, suggesting that cardioprotection cannot be provided by exercise training in this experimental model.

OBJECTIVES: Many studies have investigated the importance of oxidative stress on the cardiovascular system. In this study we evaluated the effects of central catalase inhibition on cardiopulmonary reflex in conscious Wistar rats. METHODS: Male Wistar rats were implanted with a stainless steel guide cannula in the fourth cerebral ventricle. The femoral artery and vein were cannulated for mean arterial pressure and heart rate measurement and for drug infusion, respectively. After basal mean arterial pressure and heart rate recordings, the cardiopulmonary reflex was tested with a dose of phenylbiguanide (PBG, 8 μg/kg, bolus). Cardiopulmonary reflex was evaluated before and μl15 minutes after 1.0 μl 3-amino-1,2,4-triazole (ATZ, 0.01g/100μl)0.01 g/100 μl) injection into the fourth cerebral ventricle. Vehicle treatment did not change cardiopulmonary reflex responses. RESULTS: Central ATZ significantly increased hypotensive responses without influencing the bradycardic reflex. CONCLUSION: ATZ injected into the fourth cerebral ventricle increases sympathetic inhibition but does not change the parasympathetic component of the cardiopulmonary reflex in conscious Wistar rats.