RESUMO
BACKGROUND: After brain death (BD) donors usually experience cardiac dysfunction, which is responsible for a considerable number of unused organs. Causes of this cardiac dysfunction are not fully understood. Some authors argue that autonomic storm with severe hemodynamic instability leads to inflammatory activation and myocardial dysfunction. OBJECTIVES: To investigate the hypothesis that thoracic epidural anesthesia blocks autonomic storm and improves graft condition by reducing the inflammatory response. METHODS: Twenty-eight male Wistar rats (250-350 g) allocated to four groups received saline or bupivacaine via an epidural catheter at various times in relation to brain-death induction. Brain death was induced by a sudden increase in intracranial pressure by rapid inflation of a ballon catheter in the extradural space. Blood gases, electrolytes, and lactate analyses were performed at time zero, and 3 and 6 hours. Blood leukocytes were counted at 0 and 6 hours. After 6 hours of BD, we performed euthanasia to measure vascular adhesion molecule (VCAM)-1, intracellular adhesion molecule (ICAM)-1, interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, Bcl-2 and caspase-3 on cardiac tissue. RESULTS: Thoracic epidural anesthesia was effective to block the autonomic storm with a significant difference in mean arterial pressure between the untreated (saline) and the bupivacaine group before BD (P < .05). However, no significant difference was observed for the expressions of VCAM-1, ICAM-1, TNF-α, IL-1ß, Bcl-2, and caspase-3 (P > .05). CONCLUSION: Autonomic storm did not seem to be responsible for the inflammatory changes associated with BD; thoracic epidural anesthesia did not modify the expression of inflammatory mediators although it effectively blocked the autonomic storm.
Assuntos
Anestesia Epidural , Sistema Nervoso Autônomo/fisiopatologia , Morte Encefálica , Miocardite/fisiopatologia , Animais , Masculino , Ratos , Ratos WistarRESUMO
The pericarp and seeds from fruits of Garcinia brasiliensis were subjected to extraction with hexane and ethanol. The pericarp hexane extract (PHE) and seed ethanol extract (SEE) were purified by silica gel column chromatography, which permitted isolation of the prenylated benzophenones 7-epiclusianone (1) and guttiferone-A (2), respectively. The antimicrobial activity of PHE, SEE, and compounds 1 and 2 were evaluated against Candida albicans, Staphylococcus aureus, Escherichia coli, and Bacillus cereus cultures. The minimum inhibitory concentration and minimum bactericidal concentration were established. The substances presented activity against S. aureus and B. cereus as follows: PHE, 4.0 microg/mL and 2.4 microg/mL; SEE, 10.0 microg/mL and 12.6 microg/mL; 7-epiclusianone, 1.2 microg/mL and 0.6 microg/mL; and guttiferone-A, 2.4 microg/mL and 2.4 microg/mL, respectively. The direct relationship between the lipophilic character of the structure and activity in Gram-positive bacteria was specifically observed. Therefore these extracts and prenylated benzophenones represent an interesting topic for further studies and open possibilities for an alternative control of diseases associated with Gram-positive bacteria.
Assuntos
Antibacterianos/farmacologia , Antifúngicos/farmacologia , Benzofenonas/farmacologia , Benzoquinonas/farmacologia , Garcinia , Floroglucinol/farmacologia , Extratos Vegetais/farmacologia , Antibacterianos/isolamento & purificação , Antifúngicos/isolamento & purificação , Bactérias/efeitos dos fármacos , Benzofenonas/isolamento & purificação , Benzoquinonas/isolamento & purificação , Candida albicans/efeitos dos fármacos , Frutas , Garcinia/química , Testes de Sensibilidade Microbiana , Floroglucinol/análogos & derivados , Floroglucinol/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , SementesRESUMO
BACKGROUND: We recently demonstrated that aldose reductase inhibition was effective in restoring the reduced migratory capacity of leukocytes in diabetic rats. To investigate the mechanism(s) involved in the restoring effect, we used minalrestat, an aldose reductase inhibitor. METHODS: In sodium pentobarbital-anesthetized (40 mg/kg, intraperitoneally) alloxan-diabetic or galactosemic male Wistar rats, the internal spermatic fascia was exteriorized, and the number of leukocytes rolling along the venular endothelium and the number of leukocytes sticking to the vascular wall after topical application of zymosan-activated plasma or leukotriene B(4) (1 ng/ml), as well as after the application of a local irritant stimulus (carrageenan, 100 microg), were determined using intravital microscopy. Data from animals that were treated with and those that were not treated with minalrestat (10 mg/kg/d by gavage) were compared. RESULTS: The reduced number of leukocytes rolling along the venular endothelium (by about 70%) and the number of adhered and migrated leukocytes in postcapillary venules (by 60%) were significantly restored to control values after minalrestat treatment. Total or differential leukocyte counts, venular blood flow velocity or wall shear rate were not altered by minalrestat treatment. The expression of ICAM-1 and P-selectin, cell adhesion molecules involved in the interaction of leukocyte-endothelium, reduced in diabetic rats was restored by minalrestat treatment. CONCLUSION: We conclude that an enhanced flux through the polyol pathway might be involved in the reduced expression of ICAM-1 and P-selectin contributing to the impaired leukocyte-endothelial interactions in diabetes mellitus and that aldose reductase inhibition restores the defect, restoring the reduced expression.
Assuntos
Aldeído Redutase/antagonistas & inibidores , Diabetes Mellitus Experimental/fisiopatologia , Imidas/farmacologia , Migração e Rolagem de Leucócitos/efeitos dos fármacos , Quinolonas/farmacologia , Animais , Velocidade do Fluxo Sanguíneo/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Frutose/sangue , Galactitol/sangue , Galactose/sangue , Galactosemias/fisiopatologia , Frequência Cardíaca/efeitos dos fármacos , Imuno-Histoquímica , Molécula 1 de Adesão Intercelular/sangue , Contagem de Leucócitos , Migração e Rolagem de Leucócitos/fisiologia , Masculino , Selectina-P/sangue , Ratos , Ratos Wistar , Sorbitol/sangueRESUMO
One of the most devastating secondary complications of diabetes is the blunted inflammatory response that becomes evident even in the very early stages of poorly controlled diabetes mellitus. While the etiology of this diminished response is not clearly understood, it has been linked to a decrease in the respiratory burst of neutrophils, as well as a decrease in microvessel response to inflammatory mediators and defective leukocyte-endothelial interactions. Using video microscopy to visualize vessels of the internal spermatic fascia, we have characterized leukocyte-endothelial interactions in alloxan-induced diabetic and in galactosemic rats by quantitating the number of leukocytes rolling along the venular endothelium and the number of leukocytes sticking to the vascular wall after topical application of zymosan-activated plasma or leukotriene B(4) (1 ng/ml), as well as after the application of a local irritant stimulus (carrageenan, 100 microg). We observed that while 33 days of alloxan-induced diabetes or 7 days of galactosemia had no effect on total or differential leukocyte counts and on the wall shear rate, both treatments significantly (P<0.001) reduced the number of leukocytes rolling along the venular endothelium by about 70% and the number of adhered leukocytes in postcapillary venules by 60%. These effects were not observed in diabetic and galactosemic animals treated with an aldose reductase inhibitor. The results suggest that impaired leukocyte-endothelial cell interactions are a consequence of an enhanced flux through the polyol pathway.