An experimental study of ascorbic acid effects in acute renal failure under general anesthesia

Abstract Purpose: To evaluate the preventive effect of ascorbic acid on sevoflurane-induced acute renal failure in an experimental rat model. Methods: Twenty-four adult male Wistar rats were randomly distributed into three groups. Subjects were allocated into 3 groups: Group I received sevoflurane only, whereas Groups II and III had moderate (150 mg/kg) and high (300 mg/kg) doses of AA in addition to sevoflurane, respectively. Rhabdomyolysis and myohemoglobinuric ARF was formed by intramuscular administration of glycerol on the upper hind limb on the 15th minute of inhalation anesthesia. Biochemical parameters consisted of serum levels of blood urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), total antioxidant capacity (TAC), and protein carbonyl content. Histopathological variables were tubular necrosis, fibrin, and cast formation. Results: NGAL levels were significantly lower in Group III than Group II and Group I. On the other hand, TAC, PCO, urea and creatinine levels were notably higher in Group I compared with Groups II and III. There was a significant difference between 3 groups on frequencies of acute tubular necrosis (p=0.003), fibrin (p<0.001) and cast (p<0.001). Acute tubular necrosis and fibrin formation were more prominent in Group I. Casts were more common in Groups II and III. Conclusions: The ascorbic acid serve as a prophylactic agent against renal damage in patients receiving sevoflurane anesthesia and higher doses were associated with more apparent protective effects.

Comparisons of the effects of the sevoflurane and propofol on acute ischemia reperfusion and DNA damages in rabbits / Comparações dos efeitos de sevoflurano e propofol sobre isquemia-reperfusão aguda e danos ao DNA em coelhos

Abstract Background and objectives: The aim of this study was to compare the effects of sevoflurane and propofol anesthesia on oxidative DNA damage that occurs in low-extremity ischemia and is caused by tourniquet application. Methods: Fourteen New Zealand rabbits were randomly allocated into two equal groups. Group S (n = 7) received sevoflurane (2.5-4 percent) inhalation and Group P (n = 7) received a propofol infusion (1-2 mg·kg-1·min-1), after which a pneumatic tourniquet was placed on the right lower extremity. Blood samples were collected prior to tourniquet placement (baseline), 120 min after ischemia, 15 min after ischemia and 120 minutes (min) after ischemia. Malondialdehyde (MDA) levels were analyzed to determine lipid peroxidation, and single cell gel electrophoresis (SCGE) was used to determine DNA damage. Results: At 15 min after ischemia, the MDA levels in Group P (8.15 ± 2.61 µM) were higher than baseline (6.26 ± 3.19 µM, p = 0.026) and Group S (4.98 ± 0.77 µM, p = 0.01). DNA damage was similar in both groups, although DNA damage was higher than baseline (tail moment 0.63 ± 0.27, tail intensity 3.76 ± 1.26) in Group P at the 15th minute of reperfusion (tail moment 1.05 ± 0.45, p = 0.06; tail intensity 5.33 ± 1.56, p = 0.01). The increase in tail moment and tail intensity returned to normal levels in both groups 2 hours after the termination of ischemia. Conclusion: Given that oxidative stress and genotoxic effect disappear in the late stages of reperfusion, we conclude that neither sevoflurane nor propofol can be considered superior to the other in anesthesia practices for extremity surgeries involving the use of a tourniquet.

Resumo Justificativa e objetivos: Comparar os efeitos da anestesia com sevoflurano e propofol sobre o dano oxidativo ao DNA que ocorre na isquemia de extremidade inferior e é causada pela aplicação de torniquete. Métodos: Foram alocados aleatoriamente em dois grupos iguais 14 coelhos da raça Nova Zelândia. Grupo S (n = 7) recebeu inalação de sevoflurano (2,5-4%) e Grupo P (n = 7) recebeu perfusão de propofol (1-2 mg·kg-1·min-1), logo após um torniquete pneumático foi colocado na extremidade inferior direita. Amostras de sangue foram coletadas antes da colocação do torniquete (fase basal), após 120 minutos de isquemia, 15 minutos após a isquemia e 120 minutos após a isquemia. Os níveis de malondialdeído (MDA) foram analisados para determinar a peroxidação de lipídios e eletroforese em gel de célula única (EGCU) foi usada para determinar o dano ao DNA. Resultados: Aos 15 minutos após a isquemia, os níveis de MDA no Grupo P (8,15 ± 2,61 µM) foram superiores aos da fase basal (6,26 ± 3,19 µM, p = 0,026) e dp Grupo S (4,98 ± 0,77 µM, p = 0,01). O dano causado ao DNA foi semelhante nos dois grupos, embora tenha sido maior do que na fase basal (momento da cauda 0,63 ± 0,27, intensidade da cauda 3,76 ± 1,26) no Grupo P no 15 minutos de reperfusão (momento da cauda 1,05 ± 0,45, p = 0,06; intensidade da cauda 5,33 ± 1,56, p = 0,01). O aumento no momento da cauda e a intensidade da cauda voltaram aos níveis normais nos dois grupos duas horas após o término da isquemia. Conclusão: Como o estresse oxidativo e o efeito genotóxico desaparecem nos estágios finais da reperfusão, concluímos que não há superioridade tanto de sevoflurano quanto de propofol em práticas de anestesia para procedimentos cirúrgicos de extremidades que envolvem o uso de torniquete.

Anesthesia with propofol and sevoflurane on postoperative cognitive function of elderly patients undergoing general thoracic surgery

This study is to analyze the effects and variations on cognitive function for elderly patients undergoing general thoracic surgery, who accepted the anesthesia with propofol and sevoflurane. A total of 500 elderly general thoracic surgical patients were selected randomly, all receiving the propofol anesthesia [Propofol group]. Meanwhile, another totality of 500 patients in the same condition and period were selected and accepted the sevoflurane anesthesia [Sevoflurane group]. Mini-mental state examination [MMSE] and recovery quality after anesthesia were compared among the patients in both groups respectively at the time of pre-operation and 1 h, 6 h and 12 h after surgery. There was no statistic difference in preoperative MMES of patients in both two groups [P<0.05]; while the results of postoperative MMSE showed that both Propofol group and Sevoflurane group had a certain statistical difference, and that in Propofol group was larger compared that in Sevoflurane group. Moreover, P<0.05 was obtained on comparing the MMSE at the time of 1h, 6h and 12h after surgery and that at pre-operation, revealing statistical significance. Either propofol or sevoflurane, to certain extent, can affect patients' cognitive function when they are applied in the general thoracic surgery for elderly patients. However, the influence of propofol on cognitive function is relatively smaller, which presents a better application value

Sevoflurane preconditioning during myocardial ischemia-reperfusion reduces infarct size and preserves autonomic control of circulation in rats

ABSTRACT PURPOSE: To investigate the myocardial ischemia-reperfusion with sevoflurane anesthetic preconditioning (APC) would present beneficial effects on autonomic and cardiac function indexes after the acute phase of a myocardial ischemia-reperfusion. METHODS: Twenty Wistar rats were allocated in three groups: control (CON, n=10), myocardial infarction with sevoflurane (SEV, n=5) and infarcted without sevoflurane (INF, n=5). Myocardial ischemia (60 min) and reperfusion were performed by temporary coronary occlusion. Twenty-one days later, the systolic and diastolic function were evaluated by echocardiography; spectral analysis of the systolic arterial pressure (SAPV) and heart rate variability (HRV) were assessed. After the recording period, the infarct size (IS) was evaluated. RESULTS: The INF group presented greater cardiac dysfunction and increased sympathetic modulation of the SAPV, as well as decreased alpha index and worse vagal modulation of the HRV. The SEV group exhibited attenuation of the systolic and diastolic dysfunction and preserved vagal modulation (square root of the mean squared differences of successive R-R intervals and high frequency) of HRV, as well as a smaller IS. CONCLUSION: Sevoflurane preconditioning better preserved the cardiac function and autonomic modulation of the heart in post-acute myocardial infarction period.

Pulse pressure variation and stroke volume variation under different inhaled concentrations of isoflurane, sevoflurane and desflurane in pigs undergoing hemorrhage

OBJECTIVES: Inhalant anesthesia induces dose-dependent cardiovascular depression, but whether fluid responsiveness is differentially influenced by the inhalant agent and plasma volemia remains unknown. The aim of this study was to compare the effects of isoflurane, sevoflurane and desflurane on pulse pressure variation and stroke volume variation in pigs undergoing hemorrhage. METHODS: Twenty-five pigs were randomly anesthetized with isoflurane, sevoflurane or desflurane. Hemodynamic and echocardiographic data were registered sequentially at minimum alveolar concentrations of 1.00 (M1), 1.25 (M2), and 1.00 (M3). Then, following withdrawal of 30% of the estimated blood volume, these data were registered at a minimum alveolar concentrations of 1.00 (M4) and 1.25 (M5). RESULTS: The minimum alveolar concentration increase from 1.00 to 1.25 (M2) decreased the cardiac index and increased the central venous pressure, but only modest changes in mean arterial pressure, pulse pressure variation and stroke volume variation were observed in all groups from M1 to M2. A significant decrease in mean arterial pressure was only observed with desflurane. Following blood loss (M4), pulse pressure variation, stroke volume variation and central venous pressure increased (p <0.001) and mean arterial pressure decreased in all groups. Under hypovolemia, the cardiac index decreased with the increase of anesthesia depth in a similar manner in all groups. CONCLUSION: The effects of desflurane, sevoflurane and isoflurane on pulse pressure variation and stroke volume variation were not different during normovolemia or hypovolemia.

Mechanisms of the beneficial effect of sevoflurane in liver ischemia/reperfusion injury

PURPOSE: To evaluate the underlying mechanisms by which sevoflurane protects the liver against ischemia/reperfusion injury evaluate the mechanism by which sevoflurane exerts this protective effect. METHODS: Twenty-six rats were subjected to partial ischemia/reperfusion injury for 1h: one group received no treatment, one group received sevoflurane, and sham group of animals received laparotomy only. Four hours after reperfusion, levels of alanine and aspartate aminotransferases, tumor necrosis factor-a, and interleukins 6 and 10 were measured. Analyses of mitochondrial oxidation and phosphorylation, malondialdehyde content, histology, and pulmonary vascular permeability were performed. RESULTS: Serum levels of alanine and aspartate aminotransferases were significantly lower in the sevoflurane group compared to untreated controls (p<0.05). The sevoflurane group also showed preservation of liver mitochondrial function compared to untreated controls (p<0.05). Sevoflurane administration did not alter increases in serum levels of tumor necrosis factor-a, and interleukins 6 and 10. Sevoflurane treatment significantly reduced the coagulative necrosis induced by ischemia/reperfusion (p<0.05). Pulmonary vascular permeability was preserved in the sevoflurane group compared to untreated controls. CONCLUSION: Sevoflurane administration protects the liver against ischemia/reperfusion injury, via preservation of mitochondrial function, and also preserves lung vascular permeability.

Role of mitochondrial ATP-sensitive potassium channel-mediated PKC-ε in delayed protection against myocardial ischemia/reperfusion injury in isolated hearts of sevoflurane-preconditioned rats

This study aimed to determine the role of mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels and protein kinase C (PKC)-ε in the delayed protective effects of sevoflurane preconditioning using Langendorff isolated heart perfusion models. Fifty-four isolated perfused rat hearts were randomly divided into 6 groups (n=9). The rats were exposed for 60 min to 2.5% sevoflurane (the second window of protection group, SWOP group) or 33% oxygen inhalation (I/R group) 24 h before coronary occlusion. The control group (CON) and the sevoflurane group (SEVO) group were exposed to 33% oxygen and 2.5% sevoflurane for 60 min, respectively, without coronary occlusion. The mitoKATP channel inhibitor 5-hydroxydecanoate (5-HD) was given 30 min before sevoflurane preconditioning (5-HD+SWOP group). Cardiac function indices, infarct sizes, serum cardiac troponin I (cTnI) concentrations, and the expression levels of phosphorylated PKC-ε (p-PKC-ε) and caspase-8 were measured. Cardiac function was unchanged, p-PKC-ε expression was upregulated, caspase-8 expression was downregulated, cTnI concentrations were decreased, and the infarcts were significantly smaller (P<0.05) in the SWOP group compared with the I/R group. Cardiac function was worse, p-PKC-ε expression was downregulated, caspase-8 expression was upregulated, cTnI concentration was increased and infarcts were larger in the 5-HD+SWOP group (P<0.05) compared with the SWOP group. The results suggest that mitoKATP channels are involved in the myocardial protective effects of sevoflurane in preconditioning against I/R injury, by regulating PKC-ε phosphorylation before ischemia, and by downregulating caspase-8 during reperfusion.

General anesthesia type does not influence serum levels of neutrophil gelatinase-associated lipocalin during the perioperative period in video laparoscopic bariatric surgery

OBJECTIVES: Video laparoscopic bariatric surgery is the preferred surgical technique for treating morbid obesity. However, pneumoperitoneum can pose risks to the kidneys by causing a decrease in renal blood flow. Furthermore, as in other surgical procedures, laparoscopic bariatric surgery triggers an acute inflammatory response. Neutrophil gelatinase-associated lipocalin is an early and accurate biomarker of renal injury, as well as of the inflammatory response. Anesthetic drugs could offer some protection for the kidneys and could attenuate the acute inflammatory response from surgical trauma. The objective of this study was to compare the effects of two types of anesthetics, propofol and sevoflurane, on the serum levels of neutrophil gelatinase-associated lipocalin during the perioperative period in laparoscopic bariatric surgery. METHODS: Sixty-four patients scheduled for laparoscopic bariatric surgery were randomized into two anesthesia groups and were administered either total intravenous anesthesia (propofol) or inhalation anesthesia (sevoflurane). In the perioperative period, blood samples were collected at three time points (before anesthesia, 6 hours after pneumoperitoneum and 24 hours after pneumoperitoneum) and urine output was measured for 24 hours. Acute kidney injuries were evaluated by examining both the clinical and laboratory parameters during the postoperative period. The differences between the groups were compared using non-parametric tests. ReBEC (http://www.ensaiosclinicos.gov.br/rg/recruiting/): RBR-8wt2fy RESULTS: None of the patients developed an acute kidney injury during the study and no significant differences were found between the serum neutrophil gelatinase-associated lipocalin levels of the groups during the perioperative period. CONCLUSION: The choice of anesthetic drug, either propofol or sevoflurane, did not affect the serum levels of neutrophil gelatinase-associated lipocalin during the perioperative ...

Comparação do efeito de sevoflurano e propofol na oxigenação durante a transição gradual para ventilação monopulmonar / Comparison of the effect of sevoflurane and propofol on oxygenation during gradual transition to one-lung ventilation / Comparación del efecto de sevoflurano y propofol en la oxigenación durante la transición gradual para la ventilación monopulmonar

Justificativa e objetivo: sabe-se que a vasoconstrição pulmonar hipóxica aumenta como resultado de desafios hipóxicos regionais intermitentes. O objetivo deste estudo foi comparar os efeitos de sevoflurano e propofol na oxigenação e fração de shunt durante a ventilação monopulmonar em um novo modelo de hipóxia pré-condicionado antes da ventilação monopulmonar. Métodos: foram anestesiados intraperitonealmente antes das canulações venosa e arterial e traqueostomizados 16 ratos albinos Wistar. Os animais foram randomicamente distribuídos para receber perfusão de sevoflurano a 2% ou 10 mg/kg/h de propofol e ventilados com oxigênio a 100%, a uma taxa inspiratória de 80 respirações/minuto por 30 minutos. Três ciclos de ventilação monopulmonar e ventilação de ambos os pulmões foram feitos e a ventilação monopulmonar foi continuada por 15 min. Amostras de gasometria arterial foram obtidas da seguinte forma: após punção e traqueotomia, após 30 minutos de tratamento com sevoflurano ou propofol e aos cinco e 15 minutos de ventilação monopulmonar. Resultados: os níveis de PaO2 foram maiores e as frações de shunt menores nos ratos que receberam propofol em comparação com os ratos tratados com sevoflurano, mas a diferença não foi significante. Os dois grupos foram comparáveis em termos de PaCO2. Conclusões: os efeitos similares de sevoflurano e propofol na PaO2 durante a ventilacão monopulmonar após pré-condicionamento hipóxico podem ter resultado de outras causas além da inibição da vasoconstrição pulmonar hipóxica. A transição gradual para a ventilação monopulmonar é uma técnica nova de pré-condicionamento de experimentos para ...

Background: It is known that hypoxic pulmonary vasoconstriction increases as a result of intermittent regional hypoxic challenges. The aim of this study was to compare the effects of sevoflurane and propofol on oxygenation and shunt fraction during one-lung ventilation in a novel model of hypoxic preconditioning before one-lung ventilation. Methods: Sixteen Wistar-albino rats were anesthetized intra-peritoneally before venous and arterial cannulations and tracheotomized. The animals were randomly allocated to receive either sevoflurane 2% or 10 mg/kg/h propofol infusion and ventilated with 100% oxygen at an inspiratory rate of 80 breaths/min for 30 min. Three cycles of one-lung ventilation and two-lung ventilation were performed and one-lung ventilation was continued for 15 min. Arterial blood gas samples were obtained as follows: after cannulation and tracheotomy, following 30 min of treatment with sevoflurane or propofol, and at the 5th and 15th min of one-lung ventilation. Results: The PaO2 levels were higher and shunt fractions were lower in rats receiving propofol compared to rats treated with sevoflurane but the difference was not significant; the two groups were comparable in terms of PaCO2. Conclusions: The similar effects of sevoflurane and propofol on PaO2 during one-lung ventilation following hypoxic preconditioning may be due to other causes beside the inhibition of hypoxic pulmonary vasoconstriction. Gradual transition to one-lung ventilation is a novel technique for preconditioning experiments for one-lung ventilation. .

Justificación y objetivo: se conoce que la vasoconstricción pulmonar hipóxica aumenta como resultado de los retos hipóxicos regionales intermitentes. El objetivo de este estudio fue comparar los efectos del sevoflurano y del propofol en la oxigenación y fracción de shunt durante la ventilación monopulmonar, en un nuevo modelo de hipoxia preacondicionado antes de la ventilación monopulmonar. Métodos: dieciséis ratones albinos Wistar fueron anestesiados intraperitonealmente antes de las canalizaciones venosa y arterial, y fueron traqueostomizados. Los animales fueron aleatoriamente distribuidos para recibir una perfusión de sevoflurano al 2% o 10 mg/kg/h de propofol y ventilados con oxigeno al 100%, a una tasa inspiratoria de 80 rpm durante 30min. Se realiza-ron 3 ciclos de ventilación monopulmonar y ventilación de ambos pulmones y la ventilación monopulmonar se continuó durante 15 min. Se obtuvieron muestras de gasometría arterial de la siguiente forma: posteriormente a la punción y a la traqueotomia, y después de 30 min de tratamiento con sevoflurano o propofol, y a los 5 y 15 min de ventilación monopulmonar. Resultados: los niveles de PaO2 fueron más elevados y las fracciones de shunt menores en los ratones que recibieron propofol en comparación con los ratones tratados con sevoflurano, pero la diferencia no fue significativa, ya que los 2 grupos fueron comparables en términos de PaCO2. Conclusiones: los efectos similares de sevoflurano y propofol en la PaO2 durante la ventilación monopulmonar después del preacondicionamiento hipóxico pueden deberse a otras causas ade-más de por la inhibición de la vasoconstricción pulmonar hipóxica. La transición gradual hacia la ventilación monopulmonar es una técnica nueva de preacondicionamiento de experimentos para la ventilación ...

Compositional studies and Biological activities of Perovskia abrotanoides Kar. oils

BACKGROUND: Current study has been designed to evaluate the chemical composition of essential and fixed oils from stem and leaves of Perovskia abrotanoides and antioxidant and antimicrobial activities of these oils. RESULTS: GC-MS analysis of essential oil identified 19 compounds with (E)-9-dodecenal being the major component in stem and hexadecanoic acid in leaves. In contrast, GC-MS analysis of fixed oil showed 40 constituents with α-amyrin the major component in stem and α-copaene in leaves. The antioxidant activity showed the highest value of 76.7% in essential oil from leaves in comparison with fixed oil from stem (45.9%) through inhibition of peroxidation in linoleic acid system. The antimicrobial assay tested on different microorganisms (e.g. E. coli, S. aureus, B. cereus, Nitrospira, S. epidermis, A. niger, A. flavus and C. albicans) showed the higher inhibition zone at essential oil from leaves (15.2 mm on B. cereus) as compared to fixed oil from stem (8.34 mm onS. aureus) and leaves (11.2 mm on S. aureus). CONCLUSIONS: The present study revealed the fact that essential oil analyzed from Perovskia abrotanoides stem and leaves could be a promising source of natural products with potential antioxidant and antimicrobial activities, as compared to fixed oil.

Renal histology and immunohistochemistry after acute hemorrhage in rats under sevoflurane and ketoprofen effect / Histologia e imuno-histoquímica renais após hemorragia aguda em ratos sob efeito do sevoflurano e cetoprofeno

PURPOSE: To investigate the influence of intravenous nonselective cyclooxygenase inhibitor, ketoprofen (keto), on kidney histological changes and kidney cytokines, tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1), levels after hemorrhage of 30 percent of volemia (three times 10 percent, intervals of 10 min) in rats. METHODS: Under sevoflurane (sevo) anesthesia, sevo and sevo+keto groups (10 rats each) were instrumented for Ringer solution (5mL/kg/h) administration and mean arterial pressure (MAP) evaluation, plus keto (1.5mg/kg) administration in sevo+keto group in the beginning of anesthesia. Rectal temperature was continuously measured. The baseline data of temperature and MAP were collected at the first hemorrhage (T1), the third hemorrhage (T2) and 30min after T2 (T3). Bilateral nephrectomy was achieved for histology and immunohistochemistry. RESULTS: In both groups, temperature and MAP diminished from initial values. Hypothermia was greater in sevo group (p=0.0002). Tubular necrosis was more frequent in sevo group (p=0.02). The studied cytokines were equally present in the kidneys of both groups. CONCLUSION: Ketoprofen was more protective to the rat kidney in condition of anesthesia with sevoflurane and hypovolemia, but it seems that TNF-α and IL-1 were not involved in that protection.

OBJETIVO: Investigar a influência do inibidor não-seletivo da ciclooxigenase, cetoprofeno (ceto) intravenoso, em alterações histológicas e dos níveis das citocinas renais - fator α de necrose tumoral (TNF- α) e interleucina 1 (IL-1) - após hemorragia de 30 por cento da volemia (10 por cento, três vezes, em intervalos de 10 min). MÉTODOS: Sob anestesia com sevoflurano (sevo), os grupos sevo e sevo+ceto (10 ratos cada) foram preparados cirurgicamente para leitura de pressão arterial média (PAM) e administração de solução de Ringer (5 mL/kg/h) e de cetoprofeno (1,5 mg/kg), no início da anestesia, no grupo sevo+ceto. Mediu-se temperatura retal continuamente. Os valores de temperatura e PAM foram observados antes da primeira hemorragia (T1), após a terceira hemorragia (T2) e 30 min após T2 (T3). Realizada nefrectomia bilateral nos dois grupos para análise histológica e imuno-histoquímica. RESULTADOS: Nos dois grupos, temperatura e PAM diminuíram com relação aos valores basais. Hipotermia foi mais acentuada no grupo sevo (p=0,0002). Necrose tubular foi mais frequente no grupo sevo (p=0,02). As citocinas estiveram igualmente presentes nos rins dos dois grupos. CONCLUSÃO: Cetoprofeno foi mais protetor no rim de rato durante anestesia com sevoflurano e hipovolemia, porém parece que TNF- α e IL-1 não estão envolvidas nessa proteção.

In vitro antifungal activity of fatty acid methyl esters of the seeds of Annona cornifolia A.St.-Hil. (Annonaceae) against pathogenic fungus Paracoccidioides brasiliensis / Atividade antifúngica in vitro dos ésteres metílicos de ácidos graxos das sementes de Annona cornifolia A.St.-Hil. (Annonaceae) sobre o fungo patogênico Paracoccidioides brasiliensis

INTRODUCTION: Fatty acids are abundant in vegetable oils. They are known to have antibacterial and antifungal properties. METHODS: Antifungal susceptibility was evaluated by broth microdilution assay following CLSI (formerly the NCCLS) guidelines against 16 fungal strains of clinical interest. RESULTS: In this work, fatty acid methyl esters (FAME) was able to inhibit 12 clinical strains of the pathogenic fungus Paracoccidioides brasiliensis and were also active in the bioautographic assay against Cladosporium sphaerospermum. CONCLUSIONS: FAME was a more potent antifungal than trimethoprim-sulfamethoxazole against P. brasiliensis under the experimental conditions tested.

INTRODUÇÃO: Os ácidos graxos são abundantes em óleos vegetais. Eles são conhecidos por suas propriedades antibacterianas e antifúngicas. MÉTODOS: A suscetibilidade a antifúngicos foi avaliada pelo ensaio de microdiluição em caldo de acordo com CLSI (anteriormente NCCLS) sobre 16 isolados de interesse clínico. RESULTADOS: Nesse trabalho, os ésteres metílicos de ácidos graxos (FAME) inibiram doze isolados clínicos do fungo patogênico Paracoccidioides brasiliensis, e também foi muito ativo no ensaio de bioautografia sobre o fungo Cladosporium sphaerospermum. CONCLUSÕES: FAME foi um antifúngico mais potente do que sulfametoxazol-trimetoprim contra P. brasiliensis, nas condições utilizadas no presente trabalho.

Comparison of S100β levels, and their correlation with hemodynamic indices in patients undergoing coronary artery bypass grafting with three different anesthetic techniques.

Cardiac surgery with aid of cardiopulmonary bypass (CPB) is associated with neurological dysfunction. The presence of cerebrospecific protein S100β in serum is an indicator of cerebral damage. This study was designed to evaluate the influence of three different anesthesia techniques, on S100β levels, in patients undergoing coronary artery bypass grafting on CPB. A total of 180 patients were divided into three groups - each of who received sevoflurane, isoflurane and total intravenous anesthesia as part of the anesthetic technique, respectively. S100 were evaluated from venous sample at following time intervals - prior to induction of anesthesia (T1), after coming off CPB (T2); 12 h after aortic cross clamping (T3) and 24 h after aortic cross clamping (T4). In all three groups, maximal rise in S100β levels occurred after CPB which gradually declined over next 24 h, the levels at 24 h post-AOXC being significantly higher than baseline levels. Significantly low levels of S100β were noted at all postdose hours in the sevoflurane group, as compared to the total intravenous anesthesia (TIVA) group, and at 12 and 24 h postaortic cross clamp, in comparison to the isoflurane group. Comparing the isoflurane group with the TIVA group, the S100 levels were lower in the isoflurane group only at 24 h postaortic cross clamp. It was concluded that maximum rise in S100β levels occurs immediately after CPB with a gradual decline in next 24 h. The rise in S100β levels is significantly less in patients administered sevoflurane in comparison to isoflurane or TIVA. Hemodynamic parameters had no influence on the S100β levels during the first 24 h after surgery.

Metabolic and oxidative effects of sevoflurane and propofol in children undergoing surgery for congenital heart disease / Efeitos metabólicos e oxidativos do sevoflurano e do propofol em crianças portadoras de cardiopatia congênita submetidas à cirurgia

PURPOSE: To evaluate the metabolic and oxidative effects of sevoflurane and propofol in children undergoing surgery for correction of congenital heart disease. METHODS: Twenty children with acyanotic congenital heart disease, scheduled for elective cardiac surgery with cardiopulmonary bypass, age range 1 day to 14 years were randomly assigned to 2 groups: Group GP, programmed to receive total intravenous anesthesia with propofol and group GS scheduled to use balanced anesthesia with sevoflurane. Exclusion criteria were cyanotic heart disease or complex, association with other malformations, severe systemic diseases, infection or children undergoing treatment and palliative or emergency surgery. Blood samples were collected at three different time-points: T0, after radial artery cannulation, T1, 30 minutes after cardiopulmonary bypass (CPB) launch and T2, at the end of procedure. Parameters analyzed included thiobarbituric acid-reactive substance (TBARS), glutathione (GLN), lactate and pyruvate plasmatic concentrations. RESULTS: TBARS, GSH, lactate and pyruvate concentrations did not change significantly by Friedman´s test. Lactate/pyruvate ratio (L/P) was >10 in both groups. There was a moderate Pearson correlation for TBARS, in T1 (r=0.50; p=0.13) e T2 (r=0.51;p=0.12). Pearson correlation was high between groups during CPB (T1) for lactate (r=0.68; p=0.02), pyruvate (r=0.75; p=0.01) and L/P ratio (r=0.83; p=0.003). CONCLUSION: Anesthetic techniques investigated in this study showed a similar pattern, with no increase in metabolic substrates and oxidative stress during surgical correction of congenital heart defects in non-cyanotic children.

OBJETIVO: Avaliar os efeitos metabólicos e oxidativos da anestesia com sevoflurano ou propofol em crianças portadoras de cardiopatia congênita, submetidas à cirurgia eletiva. MÉTODOS: Vinte crianças com cardiopatia congênita acianótica, agendadas para a cirurgia cardíaca eletiva com circulação extracorpórea (CEC), idades 1 dia-14 anos, foram distribuídas aleatoriamente em dois grupos: Grupo GP (anestesia venosa total com propofol) e grupo GS (anestesia balanceada com sevoflurano). Critérios de exclusão foram: doença cardíaca cianótica ou complexa, associação com outras malformações, doença sistêmica grave, infecção ou crianças submetidas a tratamento e cuidados paliativos ou cirurgia de emergência. Amostras de sangue foram coletadas em três horários diferentes: T0, após a canulação da artéria radial, T1, 30 minutos após o início da CEC e T2, no final do procedimento. Parâmetros analisados: substâncias reativas ao ácido tiobarbitúrico (TBARS), glutationa (GLN), lactato e piruvato. RESULTADOS: As concentrações de TBARS, GSH, lactato e piruvato não foram diferentes (teste de Friedman). A razão Lactato/piruvato (L/P) foi >10 em ambos os grupos. Houve uma correlação de Pearson moderada no TBARS, em T1 (r = 0,50, p = 0,13) e T2 (r = 0,51, p = 0,12). A correlação de Pearson foi alta entre os grupos durante a CEC (T1) para lactato (r=0,68, p=0,02), piruvato (r=0,75, p=0,01) e relação L/P (r =0,83, p=0,003). CONCLUSÃO: As técnicas anestésicas investigadas mostraram um padrão semelhante, sem aumento de substratos metabólicos ou do estresse oxidativo durante a correção cirúrgica de cardiopatias congênitas em crianças acianóticas.

Echocardiographic evaluation and comparison of the effects of isoflurane, sevoflurane and desflurane on left ventricular relaxation indices in patients with diastolic dysfunction.

This prospective randomized study aims to evaluate and compare the effects of isoflurane, sevoflurane and desflurane (study drugs) on left ventricular (LV) diastolic function in patients with impaired LV relaxation due to ischemic heart disease using transesophageal Doppler echocardiography. After approval of the local ethics committee and informed consent, 45 patients scheduled for coronary artery bypass grafting surgery were enrolled in the study. Patients were selected by a preoperative Transthoracic Echocardiographic diagnosis of impaired relaxation or Grade 1 Diastolic Dysfunction. They randomly received fentanyl and midazolam anesthesia with 1 MAC of isoflurane (n=16), sevoflurane (n=14) or desflurane (n=15). Hemodynamic parameters and TEE derived ventricular diastolic relaxation indices before and after the study drug administration were compared. LV filling pressures were kept constant throughout the study period to exclude the effect of the loading conditions on diastolic function. Four patients in the sevoflurane group and three in the desflurane group were excluded from the study, after baseline TEE examination revealed normal diastolic filling pattern. All the three study drugs significantly reduced the systemic vascular resistance index with a significant increase in cardiac index. Mean arterial pressure was reduced by all the drugs, although the decrease was not statistically significant. Hemodynamic changes were comparable between all the three groups. In terms of LV relaxation indices, all three agents led to a significant improvement in diastolic function. Transmitral and Tissue Doppler E/A and Em/Am ratios improved significantly Transmitral and Tissue Doppler E/A and Em/Am ratios improved significantly accompanied by a significant decrease in deceleration time and isovolumetric relaxation time. The effect of all three agents on diastolic relaxation parameters was comparable. In conclusion , Isoflurane, sevoflurane and desflurane, do not appear to have a detrimental effect in patients with early diastolic dysfunction. On the contrary, these inhalational agents actually improve the LV relaxation. A significant reduction in afterload produced by these vapors can be a possible reason for these findings. The positive effect of these inhalational agents on LV relaxation can have a profound effect on the perioperative anesthetic management of patients with diastolic dysfunction.

Avaliação de parâmetros antioxidantes em ratos tratados com sevoflurano / Evaluation of antioxidant parameters in eats treated with sevoflurane / Evaluación de parámetros antioxidantes en ratones tratados con sevoflurano

JUSTIFICATIVA E OBJETIVOS: O sevoflurano é um éter halogenado com flúor que sofre biotransformação hepática através do citocromo P450 2E1. Éteres halogenados que sofrem biotransformação pelo P450 2E1 podem produzir espécies reativas do oxigênio (ERO) e promover enfraquecimento do sistema de defesa antioxidante. O objetivo deste trabalho foi investigar a relação entre a atividade das enzimas antioxidantes eritrocitárias e o sevoflurano. MÉTODO: Os animais foram distribuídos em quatro grupos: Grupo 1 controle: apenas oxigênio a 100 por cento (1 L.min-1 por 60 minutos durante 5 dias consecutivos); Grupo 2 - sevoflurane 4,0 por cento em oxigênio a 100 por cento (1 L.min-1 por 60 minutos durante 5 dias consecutivos); Grupo 3 - isoniazida (i.p.), 50 mg.kg-1 de peso corporal /dia, durante 4 dias e em seguida tratados apenas com oxigênio a 100 por cento (1 L.min-1 por 60 minutos durante 5 dias consecutivos); Grupo 4 - isoniazida por via intraperitoneal na dose de 50 mg.kg-1 de peso corporal, diariamente durante 4 dias, seguido da administração do sevoflurane a 4,0 por cento em oxigênio a 100 por cento (1 L.min-1 por 60 minutos durante 5 dias). Após 12 horas da última exposição ao sevoflurane, os animais foram sacrificados e o sangue foi coletado através da veia porta para análise da atividade das enzimas antioxidantes. RESULTADOS: Aumento da atividade específica da glicose-6-fosfato desidrogenase, diminuição da atividade específica da catalase, principalmente no grupo de animais pré-tratados com isoniazida e, em seguida, tratados com sevoflurano. A glutationa peroxidase não apresentou alteração na sua atividade. CONCLUSÕES: A interação do sevoflurano com indutores enzimáticos do citocromo P450 2E1 pode propiciar a instalação do estresse oxidativo caso a exposição se torne prolongada e repetitiva.

BACKGROUND AND OBJECTIVES: Sevoflurane is a halogenated fluorinated ether that undergoes hepatic biotransformation through cytochrome P4502E1. Halogenated ethers undergoing biotransformation by P4502E1 can produce reactive oxygen species (ROS), weakening the antioxidant defense mechanism. The objective of this study was to investigate the relationship between the activity of erythrocyte antioxidant enzymes and sevoflurane. METHODS: Animals were divided in four groups: Group 1 - control: 100 percent oxygen (1 L.min-1 for 60 min during five consecutive days); Group 2 - 4.0 percent sevoflurane in 100 percent oxygen (1 L.min-1 for 60 minutes during five consecutive days); Group 3 - isoniazid (i.p.), 50 mg.kg-1/ day for four consecutive days, followed by 100 percent oxygen (1 L.min-1 for 60 minutes during four consecutive days); Group 4 - intraperitoneal isoniazid, 50 mg.kg-1 daily for four days, followed by 4.0 percent sevoflurane in 100 percent oxygen (1 L.min-1 for 60 minutes during five days). Twelve hours after the last exposure to sevoflurane, animals were sacrificed and their blood was collected through the portal vein for analysis of antioxidant enzymes. RESULTS: An increase in the activity of glucose-6-phosphate dehydrogenase and a decrease in the activity of catalase were observed, especially in the group of animals pre-treated with isoniazid. Changes in the activity of glutathione peroxidase were not observed. CONCLUSIONS: The interaction between sevoflurane and cytochrome P450 2E1 with enzymatic inducers can lead to oxidative stress with prolonged and repetitive exposure.

JUSTIFICATIVA Y OBJETIVOS: El sevoflurano es un éter halogenado con flúor que sufre una biotransformación hepática a través del citocromo P450 2E1. Los éteres halogenados que sufren biotransformación por el P450 2E1, pueden generar especies reactivas del oxígeno (ERO) y promover el debilitamiento del sistema de defensa antioxidante. El objetivo de este trabajo fue investigar la relación entre la actividad de las enzimas antioxidantes eritrocitarias y el sevoflurano. MÉTODO: Los animales fueron distribuidos en cuatro grupos: Grupo 1 control: apenas oxígeno a 100 por ciento (1 L.min-1 por 60 minutos durante 5 días consecutivos); Grupo 2 - sevoflurano 4,0 por ciento en oxígeno a 100 por ciento (1 L.min-1 por 60 minutos durante 5 días consecutivos); Grupo 3 - isoniazida (i.p.), 50 mg.kg-1 de peso corporal /día, durante 4 días y enseguida tratados apenas con oxígeno a 100 por ciento (1 L.min-1 por 60 minutos durante 5 días consecutivos); Grupo 4 - isoniazido por vía intraperitoneal en dosis de 50 mg.kg-1 de peso corporal, diariamente durante 4 días, seguido de la administración del sevoflurano a 4,0 por ciento en oxígeno a 100 por ciento (1 L.min-1 por 60 minutos durante 5 días). Después de 12 horas de la última exposición al sevoflurano, los animales se sacrificaron y la sangre se recolectó a través de la vena porta para el análisis de la actividad de las enzimas antioxidantes. RESULTADOS: Aumento de la actividad específica de la glucosa- 6-fosfato deshidrogenasa, reducción de la actividad específica de la catalasis, principalmente en el grupo de animales pretratados con isoniazida y enseguida, tratados con sevoflurano. El glutatión peroxidasa no presentó ninguna alteración en su actividad. CONCLUSIONES: La interacción del sevoflurano con inductores enzimáticos del citocromo P450 2E1 puede propiciar la instalación del estrés oxidativo en el caso que la exposición se prolongue y sea repetitiva.

Minimum alveolar concentrations and hemodynamic effects of two different preparations of sevoflurane in pigs

BACKGROUND: Original sevoflurane (Sevo A) is made with water, while a generic sevoflurane (Sevocris) is produced with propylene glycol as a stabilizing additive. We investigated whether the original and generic sevoflurane preparations differed in terms of their minimum alveolar concentration (MAC) values and hemodynamic effects. METHODS: Sixteen pigs weighing 31.6±1.8 kg were randomly assigned to the Sevo A or Sevocris groups. After anesthesia induction via mask with the appropriate sevoflurane preparation (6 percent in 100 percent oxygen), the MAC was determined for each animal. Hemodynamic and oxygenation parameters were measured at 0.5 MAC, 1 MAC and 1.5 MAC. Histopathological analyses of lung parenchyma were performed. RESULTS: The MAC in the Sevo A group was 4.4±0.5 percent, and the MAC in the Sevocris group was 4.1±0.7 percent. Hemodynamic and metabolic parameters presented significant differences in a dose-dependent pattern as expected, but they did not differ between groups. Cardiac indices and arterial pressures decreased in both groups when the sevoflurane concentration increased from 0.5 to 1 and 1.5 MAC. The oxygen delivery index (DO2I) decreased significantly at 1.5 MAC. CONCLUSION: Propylene glycol as an additive for sevoflurane seems to be as safe as a water additive, at least in terms of hemodynamic and pulmonary effects.

Sevoflurane for central venous catheterization in non-intubated neonates.

OBJECTIVE: Sedation in neonates undergoing invasive prodedures as central venous catheterization (CVC) remains contro versial. Sevoflurane is an inhaled anesthetic whose periods of action and elimination are very short. The objective of this study was to evaluate the use of sevoflurane for sedation for central venous catheterization (CVC) in non-intubated neonates and preterms. METHODS: Thirty three (33) consecutive patients (range: 1-31 days old, 26 to 40 weeks GA, weighing 580 to 3200 g) were included over a 4 months period. Sevoflurane was progressively increased, until loss of consciousness and motor response to stimulation. FiO(2), heart rate (HR), mean arterial pressure (MAP), duration of the procedure and the ease of the procedure were recorded. RESULTS: HR was very stable, but MAP dropped significantly. No patient required intubation. The ease of the procedure was scored as average 13 times and excellent 20 times. CONCLUSION: The use of sevoflurane in neonates for CVC is feasible and achieve the goals of procedural sedation. The pharmacokinetic of sevoflurane enabled rapid adjustment of the depth of sedation. Sevoflurane appears to be a new agent at the disposal of neonatologists. Its use does not come without risks, especially for smaller preterms, which the treating clinician must anticipate.

Halogenated anaesthetics and cardiac protection in cardiac and non-cardiac anaesthesia.

Volatile anaesthetic agents have direct protective properties against ischemic myocardial damage. The implementation of these properties during clinical anaesthesia can provide an additional tool in the treatment or prevention, or both, of ischemic cardiac dysfunction in the perioperative period. A recent meta-analysis showed that desflurane and sevoflurane reduce postoperative mortality and incidence of myocardial infarction following cardiac surgery, with significant advantages in terms of postoperative cardiac troponin release, need for inotrope support, time on mechanical ventilation, intensive care unit and overall hospital stay. Multicentre, randomised clinical trials had previously demonstrated that the use of desflurane can reduce the postoperative release of cardiac troponin I, the need for inotropic support, and the number of patients requiring prolonged hospitalisation following coronary artery bypass graft surgery either with and without cardiopulmonary bypass. The American College of Cardiology/American Heart Association Guidelines recommend volatile anaesthetic agents during non-cardiac surgery for the maintenance of general anaesthesia in patients at risk for myocardial infarction. Nonetheless, evidence in non-coronary surgical settings is contradictory and will be reviewed in this paper together with the mechanisms of cardiac protection by volatile agents.

Comparison between the effect of isoflurane and sevoflurane on left ventricular diastolic function in patients with pre-existing diastolic dysfunction undergoing CABG

Inhalational anesthetics have been shown to possess a dose-dependent negative lusitropic action in experimental studies. This effect was explained by the interference of inhalational anesthetics with calcium homeostasis at several subcellular levels. However, effect of inhalational anesthetics on diastolic function in humans is still controversial. The aim of this study was to compare the effects of isoflurane and sevoflurane, two of the most commonly used inhalational anesthetics in cardiac surgery, on left ventricular diastolic indices as measured by transesophageal echocardiography [TEE] in patients with pre-existing diastolic dysfunction. After approval of the local ethics committee and obtaining written informed consent, 40 adult patients with pre-existing diastolic dysfunction were randomly allocated to one of two groups. Group I [n=20] received isoflurane, while group II [n=20] received sevoflurane as the maintenance anesthetic. Induction agents and other maintenance agents were standardized in both groups. Changes in hemodynamic parameters and echocardiographic indices before and after drug administration were compared. Filling pressures during the study were kept constant within normal range by infusion of intravenous fluids. Hemodynamic changes measured by invasive arterial pressure and pulmonary catheter were comparable between isoflurane and sevoflurane groups. Both led to a significant reduction in afterload that was accompanied by a significant increase in cardiac output and stroke volume. Transesophageal echocardiographic relaxation indices were also comparable between both groups. Transmitral and tissue Doppler E-waves increased significantly in both groups, leading to larger E/A and Em/Am ratios; whereas the deceleration time and the isovolumetric relaxation time decreased significantly. Also there was a significant increase in color M-mode transmitral propagation velocity [Vp] in both groups. Both isoflurane and sevoflurane caused an improvement in TEE diastolic indices in patients with preexisting diastolic dysfunction. However, there was no difference between the two agents. This improvement could be attributed to a reduction in left-ventricular loading conditions