DOMINGOS DIAS LOURENCO FILHO
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina - Médico
3 resultados
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- An artificial nanoemulsion carrying paclitaxel decreases the transplant heart vascular disease: A study in a rabbit graft model(2011) LOURENCO-FILHO, Domingos D.; MARANHAO, Raul C.; MENDEZ-CONTRERAS, Carlos A.; TAVARES, Elaine R.; FREITAS, Fatima R.; STOLF, Noedir A.Objective: In previous studies cholesterol-rich nanoemulsions (LDE) resembling low-density lipoprotein were shown to concentrate in atherosclerotic lesions of rabbits. Lesions were pronouncedly reduced by treatment with paclitaxel associated with LDE. This study aimed to test the hypothesis of whether LDE-paclitaxel is able to concentrate in grafted hearts of rabbits and to ameliorate coronary allograft vasculopathy after the transplantation procedure. Methods: Twenty-one New Zealand rabbits fed 0.5% cholesterol were submitted to heterotopic heart transplantation at the cervical position. All rabbits undergoing transplantation were treated with cyclosporin A (10 mg . kg(-1) . d(-1) by mouth). Eleven rabbits were treated with LDE-paclitaxel (4 mg/kg body weight paclitaxel per week administered intravenously for 6 weeks), and 10 control rabbits were treated with 3 mL/wk intravenous saline. Four control animals were injected with LDE labeled with [(14)C]-cholesteryl oleate ether to determine tissue uptake. Results: Radioactive LDE uptake by grafts was 4-fold that of native hearts. In both groups the coronary arteries of native hearts showed no stenosis, but treatment with LDE-paclitaxel reduced the degree of stenosis in grafted hearts by 50%. The arterial luminal area in grafts of the treated group was 3-fold larger than in control animals. LDE-paclitaxel treatment resulted in a 7-fold reduction of macrophage infiltration. In grafted hearts LDE-paclitaxel treatment reduced the width of the intimal layer and inhibited the destruction of the medial layer. No toxicity was observed in rabbits receiving LDE-paclitaxel treatment. Conclusions: LDE-paclitaxel improved posttransplantation injury to the grafted heart. The novel therapeutic approach for heart transplantation management validated here is thus a promising strategy to be explored in future clinical studies. (J Thorac Cardiovasc Surg 2011;141:1522-8)
- Heart Transplantation in 107 Cases of Chagas' Disease(2011) FIORELLI, A. I.; SANTOS, R. H. B.; OLIVEIRA JR., J. L.; LOURENCO-FILHO, D. D.; DIAS, R. R.; OLIVEIRA, A. S.; SILVA, M. F. A. da; AYOUB, F. L.; BACAL, F.; SOUZA, G. E. C.; BOCCHI, E. A.; STOLF, N. A. G.Introduction. Chagas' disease is endemic in South America. Objective. This research reviewed the experience with cardiac transplantation in Chagas' disease, emphasizing reactivation, immunosuppression, and mortality. Methods. Over 25 years from March 1985 to March 2010, 107/409 (26.2%) patients with Chagas' disease underwent heart transplantation, patients including 74 (71.1%) men and 72 (67.2%), in functional class IV with 33 (30.8%) on vasopressors and 17 (10.7%) on mechanical circulatory support. Results. The diagnosis of disease reactivation was performed by identifying the parasite in the myocardium (n = 23; 71.8%) in the subcutaneous tissue (n = 8; 25.0%), in blood (n = 11; 34.3%), or in central nervous tissue (n = 1; 3.1%). Hospital mortality was 17.7% (n = 19) due to infection (n = 6; 31.5%), graft dysfunction (n = 6; 31.5%), rejection (n 4; 21.1%), or sudden death (n = 2; 10.5%). Late mortality was 27 (25.2%) cases, which were distributed as: rejection (n = 6; 22.2%), infection (n = 6; 22.2%), (n = lymphoma 4; 14.8%), sarcoma (n = 2; 7.4%), for constrictive pericarditis (n = 2; 7.4%) reactivation of Chagas' disease in the central nervous system (n = 1; 7.1%). Conclusions. Transplantation in Chagas' disease has peculiar problems that differ from other etiologies due to the possibility of disease reactivation and the increased possibility of emergence of cancers. However, transplantation is the only treatment able to modify the natural progression of the disease in its terminal phase. Early diagnosis and rapid introduction of benzonidazole reverses the histological patterns. Immunosuppression, especially steroids, predisposes to the development of cancer and disease reactivation.
- Recommendations for Use of Marginal Donors in Heart Transplantation: Brazilian Association of Organs Transplantation Guideline(2011) FIORELLI, A. I.; STOLF, N. A. G.; PEGO-FERNANDES, P. M.; OLIVEIRA JUNIOR, J. L.; SANTOS, R. H. B.; CONTRERAS, C. A. M.; FILHO, D. D. L.; DINKHUYSEN, J. J.; MOREIRA, M. C. V.; MEJIA, J. A. C.; CASTRO, M. C. R.The high prevalence of heart failure has increased the candidate list for heart transplantation; however, there is a shortage of viable donated organs, which is responsible for the high mortality of patients a waiting a transplantation. Because the marginal donor presents additional risk factors, it is not considered to be an ideal donor. The use of a marginal donor is only justified in situations when the risk of patient death due to heart disease is greater than that offered by the donor. These recommendations sought to expand the supply of donors, consequently increasing the transplant rate. We selected articles based on robust evidence to provide a substratum to develop recommendations for donors who exceed the traditional acceptance criteria. Recipient survival in the immediate postoperative period is intimately linked to allograft quality. Primary allograft failure is responsible for 38% to 40% of immediate deaths after heart transplantation: therefore; marginal donor selection must be more rigorous to not increase the surgical risk. The main donor risk factors with the respective evidence levels are: cancer in the donor (B), female donor (B), donor death due to hemorrhagic stroke (B), donor age above 50 years (relative risk [RR] = 1.5) (B), weight mismatch between donor and recipient < 0.8 (RR = 1.3) (B), ischemia > 240 minutes (RR = 1.2) (B), left ventricular dysfunction with ejection fraction below 45% (B), and use of high doses of vasoactive drugs (dopamine > 15 mg/kg . mm) (B). Factors that impact recipient mortality are: age over 50 years (RR = 1.5); allograft harvest at a distance; adult recipient weighing more than 20% of the donor; high doses of vasoactive drugs (dopamine greater than 15 mg/kg . min) and ischemic time >4 hours. The use of a marginal donor is only justified when it is able to increase life expectancy compared with clinical treatment, albeit the outcomes are interior to those using an ideal donor.