Effect of methylprednisolone on perivascular pulmonary edema, inflammatory infiltrate, VEGF and TGF-beta immunoexpression in the remaining lungs of rats after left pneumonectomy

Pneumonectomy is associated with high rates of morbimortality, with postpneumonectomy pulmonary edema being one of the leading causes. An intrinsic inflammatory process following the operation has been considered in its physiopathology. The use of corticosteroids is related to prevention of this edema, but no experimental data are available to support this hypothesis. We evaluated the effect of methylprednisolone on the remaining lungs of rats submitted to left pneumonectomy concerning edema and inflammatory markers. Forty male Wistar rats weighing 300 g underwent left pneumonectomy and were randomized to receive corticosteroids or not. Methylprednisolone at a dose of 10 mg/kg was given before the surgery. After recovery, the animals were sacrificed at 48 and 72 h, when the pO2/FiO2 ratio was determined. Right lung perivascular edema was measured by the index between perivascular and vascular area and neutrophil density by manual count. Tissue expression of vascular endothelial growth factor (VEGF) and transforming growth factor-beta (TGF-β) were evaluated by immunohistochemistry light microscopy. There was perivascular edema formation after 72 h in both groups (P = 0.0031). No difference was observed between operated animals that received corticosteroids and those that did not concerning the pO2/FiO2 ratio, neutrophil density or TGF-β expression. The tissue expression of VEGF was elevated in the animals that received methylprednisolone both 48 and 72 h after surgery (P = 0.0243). Methylprednisolone was unable to enhance gas exchange and avoid an inflammatory infiltrate and TGF-β expression also showed that the inflammatory process was not correlated with pulmonary edema formation. However, the overexpression of VEGF in this group showed that methylprednisolone is related to this elevation

Effects of pneumonectomy on nitric oxide synthase expression and perivascular edema in the remaining lung of rats

Pneumonectomy is associated with high mortality and high rates of complications. Postpneumonectomy pulmonary edema is one of the leading causes of mortality. Little is known about its etiologic factors and its association with the inflammatory process. The purpose of the present study was to evaluate the role of pneumonectomy as a cause of pulmonary edema and its association with gas exchange, inflammation, nitric oxide synthase (NOS) expression and vasoconstriction. Forty-two non-specific pathogen-free Wistar rats were included in the study. Eleven animals died during or after the procedure, 21 were submitted to left pneumonectomy and 10 to sham operation. These animals were sacrificed after 48 or 72 h. Perivascular pulmonary edema was more intense in pneumonectomized rats at 72 h (P = 0.0131). Neutrophil density was lower after pneumonectomy in both groups (P = 0.0168). There was higher immunohistochemical expression of eNOS in the pneumonectomy group (P = 0.0208), but no statistically significant difference in the expression of iNOS. The lumen-wall ratio and pO2/FiO2 ratio did not differ between the operated and sham groups after pneumonectomy. Left pneumonectomy caused perivascular pulmonary edema with no elevation of immunohistochemical expression of iNOS or neutrophil density, suggesting the absence of correlation with the inflammatory process or oxidative stress. The increased expression of eNOS may suggest an intrinsic production of NO without signs of vascular reactivity.Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)CNP

Effects of different amounts of Saccharomyces cerevisiae supplementation on apparent digestibility and faecal parameters in horses fed high-roughage and high-concentrate diets

The aim of this study was to evaluate the influence of different amounts of Saccharomyces cerevisiae (SC) supplementation in high-roughage (HR) and high-concentrate (HC) diets on apparent total tract digestibility (ATTD), faecal microbial profile and faecal pH. Eight gelding miniature horses, about 36-months-old with an average weight of 113±12 kg were randomly assigned into a double 4×4 Latin Square. Two distinct experiments of 4 periods each were conducted with SC-supplementation of 0 (control), 10, 20 and 30 g (5×10 cfu/g), per animal per day. Experiment 1 used a HR diet (70% grass hay, 30% concentrate) and experiment 2 used a HC diet (30% grass hay, 70% concentrate). Each experimental period consisted of 23 days: 15 adaptation days, 5 days for data collection and a 3-day-wash-out interval between periods. Nutrient digestibility was evaluated by total faecal collection for each animal. The cellulolytic and lactic acid bacteria populations in faeces were calculated and faecal pH was measured. In the HR diet, S. cerevisiae supplementation was not associated with any changes in ATTD of nutrients, microbial profile in faeces and did not increase faecal pH values. In the HC diet, only the addition of 20 g SC reduced crude protein digestibility when compared with the control group and 30 g SC. For the other variables of digestibility the amounts of SC supplementation did not differ from control group. Furthermore, the microbial profile in faeces and faecal pH were not affected by S. cerevisiae supplementation. The present study showed that the S. cerevisiae strain used was not able to induce any changes in the equine hindgut and did not improve the fibrolytic activity with high-roughage and high-concentrate diets

In Vivo Study Of Lyophilized Bioprostheses: 3 Month Follow-up In Young Sheep [estudo In Vivo Do Comportamento De Bioprótese Liofilizada: Seguimento De 3 Meses Em Carneiros Jovens]

Objective: Glutaraldehyde is currently used in bovine pericardium bioprosthesis to improve mechanical and immunogenic properties. Lyophilization is a process that may decrease aldehyde residues in the glutaraldehyde treated pericardium decreasing cytotoxicity and enhancing resistance to calcification. The aim of this study is to evaluate bioprosthetic heart valves calcification in adolescent sheep and to study the potential of lyophilization as a mechanism to protect calcification. Methods: Two groups were evaluated: a control group in which a bovine pericardium prosthetic valve was implanted in pulmonary position and a lyophilized group in which the bovine pericardium prosthetic valve was lyophilized and further implanted. Sixteen sheeps 6 months old were submitted to the operation procedure. After 3 months the sheeps were euthanized under full anesthesia. Results: Six animals of the control group reached 95.16 ± 3.55 days and six animals in the lyophilized group reached 91.66 ± 0.81 days of postoperative evolution. Two animals had endocarditis. Right ventricle/pulmonary artery (RV/PA) mean gradient, in the control group, at the implantation was 2.04 ± 1.56 mmHg, in the lyophilization group, the RV/PA mean gradient, at the implantation was 6.61 ± 4.03 mmHg. At the explantation it increased to 7.71 ± 3.92 mmHg and 8.24 ± 6.25 mmHg, respectively, in control and lyophilization group. The average calcium content, after 3 months, in the control group was 21.6 ± 39.12 μg Ca+2/mg dry weight, compared with an average content of 41.19 ± 46.85 μg Ca+2/mg dry weight in the lyophilization group (P=0.662). Conclusion: Freeze drying of the bovine pericardium prosthesis in the pulmonary position could not demonstrate calcification mitigation over a 3 month period although decreased inflammatory infiltration over the tissue.274592599Rahimtoola, S.H., Choice of prosthetic heart valve in adults an update (2010) J Am Coll Cardiol., 55 (22), pp. 2413-2426David, T.E., Armstrong, S., Maganti, M., Hancock II bioprosthesis for aortic valve replacement: The gold standard of bioprosthetic valves durability? (2010) Ann Thorac Surg., 90 (3), pp. 775-781Clark, J.N., Ogle, M.F., Ashworth, P., Bianco, R.W., Levy, R.J., Prevention of calcification of bioprosthetic heart valve cusp and aortic wall with ethanol and aluminum chloride (2005) Ann Thorac Surg., 79 (3), pp. 897-904Ruel, M., Kulik, A., Rubens, F.D., Bédard, P., Masters, R.G., Pipe, A.L., Late incidence and determinants of reoperation in patients with prosthetic heart valves (2004) Eur J Cardiothorac Surg., 25 (3), pp. 364-370Poirer, N.C., Pelletier, L.C., Pellerin, M., Carrier, M., 15-year experience with the Carpentier-Edwards pericardial bioprosthesis (1998) Ann Thorac Surg., 66 (6 SUPPL.), pp. S57-S61Duran, C.G., Gunning, A.J., Whitehead, R., Experimental aortic valve heterotransplantation (1967) Thorax., 22 (6), pp. 510-518Duran, C.M., Whitehead, R., Gunning, A.J., Implantation of homologous and heterologous aortic valves in prosthetic vascular tubes (1969) Thorax., 24 (2), pp. 142-147Borgognoni, C.F., Maizato, M.J., Leirner, A.A., Polakiewicz, B., Beppu, M.M., Higa, O.Z., Effect of freeze-drying on the mechanical, physical and morphological properties of glutaraldehyde-treated bovine pericardium: Evaluation of freeze-dried treated bovine pericardium properties (2010) J Appl Biomater Biomech., 8 (3), pp. 186-190Maizato, M.J., Higa, O.Z., Mathor, M.B., Camillo, M.A., Spencer, P.J., Pitombo, R.N., Glutaraldehyde-treated bovine pericardium: Effects of lyophilization on cytotoxicity and residual aldehydes (2003) Artif Organs., 27 (8), pp. 692-694Flameng, W., Meuris, B., Yperman, J., de Visscher, G., Herijgers, P., Verbeken, E., Factors influencing calcification of cardiac bioprostheses in adolescent sheep (2006) J Thorac Cardiovasc Surg., 132 (1), pp. 89-98Schoen, F.J., Levy, R.J., Calcification of tissue heart valve substitutes: Progress toward understanding and prevention (2005) Ann Thorac Surg., 79 (3), pp. 1072-1080McClure, R.S., Narayanasamy, N., Wiegerinck, E., Lipsitz, S., Maloney, A., Byrne, J.G., Late outcomes for aortic valve replacement with the Carpentier-Edwards pericardial bioprosthesis: Up to 17-year follow-up in 1,000 patients (2010) Ann Thorac Surg., 89 (5), pp. 1410-1416Jamieson, W.R., Lewis, C.T., Sakwa, M.P., Cooley, D.A., Kshettry, V.R., Jones, K.W., St Jude Medical Epic porcine bioprosthesis: Results of the regulatory evaluation (2011) J Thorac Cardiovasc Surg., 141 (6), pp. 1449e2-1454e2The Italian study on the Mitroflow postoperative results (ISTHMUS): A 20-year, multicentre evaluation of Mitroflow pericardial bioprosthesis (2011) Eur J Cardiothorac Surg., 39 (1), pp. 18-26. , ISTHMUS InvestigatorsBeauchamp Jr., R.O., St Clair, M.B., Fennell, T.R., Clarke, D.O., Morgan, K.T., Kari, F.W., A critical review of the toxicology of glutaraldehyde (1992) Crit Rev Toxicol., 22 (3-4), pp. 143-174Golomb, G., Schoen, F.J., Smith, M.S., Linden, J., Dixon, M., Levy, R.J., The role of glutaraldehyde-induced cross-links in calcification of bovine pericardium used in cardiac valve bioprostheses (1987) Am J Pathol., 127 (1), pp. 122-130Guldner, N.W., Jasmund, I., Zimmermann, H., Heinlein, M., Girndt, B., Meier, V., Detoxification and endothelialization of glutaraldehyde-fixed bovine pericardium with titanium coating: A new technology for cardiovascular tissue engineering (2009) Circulation., 119 (12), pp. 1653-1660Clark, J.N., Ogle, M.F., Ashworth, P., Bianco, R.W., Levy, R.J., Prevention of calcification of bioprosthetic heart valve cusp and aortic wall with ethanol and aluminum chloride (2005) Ann Thorac Surg., 79 (3), pp. 897-904Hahn, S.K., Ohri, R., Giachelli, C.M., Anti-calcification of bovine pericardium for bioprosthetic heart valves after surface modi-fication with hyaluronic acid derivatives (2005) Biotechnol Bioprocess Eng., 10, pp. 218-224Zilla, P., Fullard, L., Trescony, P., Meinhart, J., Bezuidenhout, D., Gorlitzer, M., Glutaraldehyde detoxification of aortic wall tissue: A promising perspective for emerging bioprosthetic valve concepts (1997) J Heart Valve Dis., 6 (5), pp. 510-520Weissenstein, C., Human, P., Bezuidenhout, D., Zilla, P., Glutaraldehyde detoxification in addition to enhanced amine cross-linking dramatically reduces bioprosthetic tissue calcification in the rat model (2000) J Heart Valve Dis., 9 (2), pp. 230-240Santibáñez-Salgado, J.A., Olmos-Zúñiga, J.R., Pérez-López, M., Aboitiz-Rivera, C., Gaxiola-Gaxiola, M., Jasso-Victoria, R., Lyophilized glutaraldehyde-preserved bovine pericardium for experimental atrial septal defect closure (2010) Eur Cell Mater., 19, pp. 158-165Zilla, P., Brink, J., Human, P., Bezuidenhout, D., Prosthetic heart valvae: Catering for the few (2008) Biomaterials., 29 (4), pp. 385-40