Protocolo Clínico e Diretrizes Terapêuticas da Degeneração Macular Relacionada à Idade (forma neovascular) / Clinical Protocol and Therapeutic Guidelines of macular degeneration related to age (neovascular form)

CONTEXTO: Os PCDT são documentos que visam garantir o melhor cuidado de saúde diante do contexto brasileiro e dos recursos disponíveis no SUS. Podem ser utilizados como materiais educativos aos profissionais de saúde, auxílio administrativo aos gestores, regulamentação da conduta assistencial perante o Poder Judiciário e explicitação de direitos aos usuários do SUS. Os PCDT são os documentos oficiais do SUS que estabelecem critérios para o diagnóstico de uma doença ou agravo à saúde; tratamento preconizado, com os medicamentos e demais produtos apropriados, quando couber; posologias recomendadas; mecanismos de controle clínico; e acompanhamento e verificação dos resultados terapêuticos a serem seguidos pelos gestores do SUS. Os PCDT devem incluir recomendações de condutas, medicamentos ou produtos para as diferentes fases evolutivas da doença ou do agravo à saúde de que se tratam, bem como aqueles indicados em casos de perda de eficácia e de surgimento de intolerância ou reação adversa relevante,

Terapias actuales en la vascularización corneal / Current therapies in corneal vascularization

Una córnea transparente es esencial para una excelente visión; es por eso que es avascular. Pero existen condiciones que favorecen la invasión de neovasos al tejido corneal, como infecciones, inflamación, hipoxia, trauma, entre otras, que reducen la calidad visual y en algunos casos llegan hasta la pérdida de esta. La neovascularización corneal representa un problema importante de salud pública a nivel mundial. Se realizó una búsqueda automatizada con el objetivo de encontrar información actualizada sobre el tratamiento de la neovascularización corneal, para lo cual se utilizó la plataforma infomed. La información se resumió en el documento final. Sobre el tema, existe un progreso notable en el entendimiento de la patogénesis, el mejoramiento y la seguridad de los nuevos tratamientos. Los corticoesteroides y los agentes anti-VEGF (factor de crecimiento endotelial vascular) continúan siendo los medicamentos de primera línea, usados principalmente para evitar la formación de los nuevos vasos, no así para vasos maduros, donde la mejor opción son los procedimientos quirúrgicos o combinados. Se necesitan más estudios experimentales, y los ya existentes deben ser utilizados en ensayos clínicos para investigar sobre la dosis segura y los efectos secundarios, y así encontrar terapias radicales, más eficaces, que le den a los pacientes con neovascularización corneal la esperanza de una mejor calidad visual(AU)

A clear cornea is essential for excellent vision; that is why it is avascular. But there are conditions that favor the invasion of neovessels into the corneal tissue, such as infections, inflammation, hypoxia, trauma, among others, which reduce visual quality and in some cases even lose it. Corneal neovascularization represents a major public health problem worldwide. An automated search was carried out in order to find updated information on the treatment of corneal neovascularization, for which the infomed platform was used. The information was summarized in the final document. On the subject, there is notable progress in understanding the pathogenesis, improvement and safety of new treatments. Corticosteroids and anti-VEGF (vascular endothelial growth factor) agents continue to be the first-line drugs, used mainly to prevent the formation of new vessels, not for mature vessels, where the best option is surgical or combined procedures. More experimental studies are needed; and the existing ones should be used in clinical trials to investigate the safe dose and side effects, and thus find radical and more effective therapies that give patients with corneal neovascularization the hope of better visual quality(AU)

Cordycepin prevents the esophageal stricture formation in the alkali-burn rat model by exerting anti-inflammatory and antifibrotic effects

ABSTRACT Purpose To investigate the efficacy of cordycepin, an adenosine analogue, on prevention of esophageal damage and stricture formation due to esophageal caustic burns in rat model comparing with prednisolone. Methods Caustic esophageal burn was introduced by 37.5% of NaOH to distal esophagus. Thirty-two Wistar albino rats were divided in four groups: sham rats undergone laparotomy, treated with 0.9% NaCl; control rats injured with NaOH without cordycepin treatment; cordycepin group injured with NaOH, treated with 20 mg/kg cordycepin; prednisolone group injured with NaOH, treated with 1 mg/kg prednisolone for 28 days. Efficacy was assessed by histopathological and immunohistochemical analysis of esophageal tissues. Results Cordycepin treatment significantly decreased inflammation, granulation tissue and fibrous tissue formation and prevented formation of esophageal strictures shown by histopathological damage score and stenosis indexes compared to control group (p < 0.01). These effects are relatively more substantial than prednisolone, probably based on attenuation of elevation of proinflammatory cytokines hypoxia-inducible factor 1-alpha (HIF-1?), tumor necrosis factor alpha (TNF-?), proliferative and fibrotic factor fibroblast growth factor 2 (FGF2) and angiogenic factor vascular endothelial growth factor A (VEGFA) (p < 0.05). Conclusions The findings suggest that cordycepin has a complex multifactorial healing process in alkali-burned tissue, more successful than prednisolone in preventing the formation of esophageal strictures and may be used as a therapeutic agent in the acute phase of esophageal alkali-burn.

Vascular endothelial growth factor association with angiopoietin 1 promotes improvement in ventricular function after ischemic cardiomyopathy induced in mini pigs

Abstract Purpose: To investigate the safety and clinical, hemodynamic and tissue improvement ability in mini pigs undergoing cell and gene therapy for the treatment of acute myocardial infarction. Methods: Thirty-two mini pigs Br1 lineage, 12 months old, undergoing induction of acute myocardial infarction by occlusion of the diagonal branch of the paraconal coronary. They were divided into 4 groups: one control group and 3 treatment groups (cell therapy and gene cell therapy). Echocardiography reviews were performed on three occasions and histopathological analysis was performed after 4 weeks. Analysis of variance (ANOVA), Tukey and Wilcoxon tests, were performed. Results: Association of vascular endothelial growth factor (VEGF) with angiopoietin1 (Ang1) presented satisfactory results in the improvement of ventricular function following ischemic cardiomyopathy in mini pigs when compared to the results of the other treated groups. Conclusion: The therapy with VEGF and the combination of VEGF with Ang1, promoted recovered function of the myocardium, characterized by reduced akinetic area and induction of neovascularization.

Terapias anti-VEGF en el tratamiento de enfermedades de la retina: recomendaciones para la práctica en Colombia / Anti-VEGF therapy for retinal diseases treatment: recommendations for it practice in Colombia

Objetivo: Exponer la experiencia local sobre el tratamiento de las enfermedades retinales con terapias anti factor de crecimiento endotelial vascular (anti-VEGF) y crear conciencia en relación con la atención centrada en el paciente reconociendo el papel de los médicos especialistas en la determinación del tratamiento más apropiado basado principalmente en la evidencia científica, pero también teniendo en cuenta la experiencia y práctica exitosas en el manejo de cada paciente, con base en sus características únicas e individuales. Método: Revisión y comparación de la literatura científica con la experiencia de los autores, en el diagnóstico y tratamiento de las enfermedades que involucran inyecciones intraoculares, haciendo especial énfasis en la degeneración macular relacionada con la edad neo vascular (DMRE-NV), el edema macular diabético (EMD), la retinopatía diabética (RD), edema macular por oclusión venosa de rama de vena central de la retina (ORVR), la oclusión de vena central de la retina (OVCR) y la neo vascularización sub retiniana asociada a miopía patológica (MP). Resultados: la revisión realizada reafirma que tanto cuando hablamos de clases de medicamentos, de algoritmos de tratamiento o de perfiles de paciente, los diferentes agentes de una misma clase terapéutica pueden tener eficacias o perfiles de seguridad variables. Se debe considerar la importancia clínica que representa la valoración adecuada de los resultados pos tratamiento, pero sobre todo, la selección cuidadosa para determinar el agente y esquema más apropiado en la intención de tratar a un paciente. Si bien existen recomendaciones y guías de tratamiento para las patologías, los protocolos en el manejo individualizado y la exposición de estas experiencias de vida real se hacen necesarios, ya que no todos los pacientes ni todas las enfermedades de la retina responden de igual forma a cada agente terapéutico. Conclusión: La efi cacia y seguridad en el uso de las terapias anti-VEGF son aspectos de suma importancia cuando se trata de proporcionar una atención verdaderamente centrada en el paciente. No hay ninguna solución, intervención o alternativa terapéutica que se ajuste a todas las enfermedades oculares complejas, por lo que es importante hacer un balance que considere la evidencia disponible, la experiencia, y las expectativas de los pacientes y tratantes. Esto permitirá acceder a las alternativas terapéuticas adecuadas, en el momento adecuado siempre teniendo en mente los perfiles de eficacia, seguridad, farmacovigilancia activa y los costos asociados a las alternativas terapéuticas utilizadas en el país.

Purpose: To display local experience on treatment for retinal diseases with anti-Vascular Endothelial Growth Factor (anti-VEGF) therapies and to raise awareness regarding patient-centered care, recognizing the role of medical specialists in determining the most appropriate treatment mainly based on scientific evidence, but also considering the successful experience and practice handling each patient, based on their unique and individual characteristics. Method: Review and comparison of scientific literature according to the authors experience to diagnose and treat diseases involving intraocular injections, focusing on Neovascular Age-related Macular Degeneration (NV-AMD), Diabetic Macular Edema (DME), Diabetic Retinopathy (DR), Macular Edema due to Branch Retinal Vein Occlusion (BRVO), Central Retinal Vein Occlusion (CRVO) and Sub-retinal Neovascularization associated with Pathological Myopia (PM). Results: the review confi rms that, when speaking of drug classes, treatment algorithms or patient profi les, diff erent agents of the same therapeutic class can result in variable efficacies or safety profiles. The clinical relevance represented by the adequate assessment of post-treatment results must be considered, but specially, the careful screening to determine the most appropriate agent and regimen in the intention-to-treat a patient. Th ough recommendations and treatment guidelines for pathologies exist, protocols in individualized management and exposure of these real-life experiences are necessary, since not all patients or all retinal diseases respond in the same way to each therapeutic agent. Conclusion: Efficacy and safety using anti-VEGF therapies are extremely important when it comes to providing truly patient-centered care. There is no therapeutic solution, intervention or alternative that fi ts all complex ocular diseases, so it is important to weigh the available evidence, the experience and the expectations of both patients and prescribers. Th is will allow to get access to the appropriate therapeutic alternatives, in a timely manner, always considering the efficacy and safety profiles, active pharmacovigilance and the costs associated with the therapeutic alternatives used locally.

Cells involved in extracellular matrix remodeling after acute myocardial infarction / Células envolvidas no remodelamento da matriz extracelular após infarto agudo do miocárdio

Objective Evaluate the effects of VEGF165 gene transfer in the process of remodeling of the extracellular matrix after an acute myocardial infarct. Methods Wistar rats were submitted to myocardial infarction, after the ligation of the left descending artery, and the left ventricle ejection fraction was used to classify the infarcts into large and small. The animals were divided into groups of ten, according to the size of infarcted area (large or small), and received or not VEGF165 treatment. Evaluation of different markers was performed using immunohistochemistry and digital quantification. The primary antibodies used in the analysis were anti-fibronectin, anti-vimentin, anti-CD44, anti-E-cadherin, anti-CD24, anti-alpha-1-actin, and anti-PCNA. The results were expressed as mean and standard error, and analyzed by ANOVA, considering statistically significant if p≤0.05. Results There was a significant increase in the expression of undifferentiated cell markers, such as fibronectin (protein present in the extracellular matrix) and CD44 (glycoprotein present in the endothelial cells). However, there was decreased expression of vimentin and PCNA, indicating a possible decrease in the process of cell proliferation after treatment with VEGF165. Markers of differentiated cells, E-cadherin (adhesion protein between myocardial cells), CD24 (protein present in the blood vessels), and alpha-1-actin (specific myocyte marker), showed higher expression in the groups submitted to gene therapy, compared to non-treated group. The value obtained by the relation between alpha-1-actin and vimentin was approximately three times higher in the groups treated with VEGF165, suggesting greater tissue differentiation. Conclusion The results demonstrated the important role of myocytes in the process of tissue remodeling, confirming that VEGF165 seems to provide a protective effect in the treatment of acute myocardial infarct. .

Objetivo Avaliar os efeitos da transferência gênica do VEGF165 no processo de remodelamento da matriz extracelular após infarto agudo do miocárdio. Métodos Ratos Wistar foram submetidos ao infarto do miocárdio por ligação da artéria coronária descendente esquerda, e a fração de ejeção de ventrículo esquerdo foi utilizada para classificar os infartos em grandes e pequenos. Os animais foram divididos em grupos de dez animais, de acordo com o tamanho do infarto (grande ou pequeno), e receberam ou não tratamento com o VEGF165. A avaliação dos diferentes marcadores foi realizada por imuno-histoquímica e quantificação digital. Os anticorpos primários utilizados foram antifibronectina, antivimentina, anti- CD44, anti-E-caderina, anti-CD24, anti-alfa-1-actina e anti-PCNA. Os resultados foram representados como média e erro padrão, e analisados por ANOVA, sendo considerado estatisticamente significativo se p≤0,05. Resultados Houve aumento significativo da expressão de marcadores de células indiferenciadas, como fibronectina (proteína presente na matriz extracelular) e CD44 (glicoproteína presente nas células endoteliais). Entretanto, houve diminuição da expressão de vimentina e PCNA, indicando possível diminuição do processo de proliferação celular após o tratamento com VEGF165. Os marcadores de células diferenciadas, E-caderina (proteína de adesão entre as células do miocárdio), CD24 (proteína presente nos vasos sanguíneos) e alfa-1-actina (marcador especifico de miócitos) também apresentaram maior expressão nos grupos submetidos à terapia gênica, comparativamente com o grupo não tratado. O valor obtido pela relação entre alfa-1-actina e vimentina foi aproximadamente três vezes maior nos grupos tratados com VEGF165, indicando maior diferenciação tecidual. Conclusão O papel dos miócitos se mostrou importante no processo de remodelamento tecidual, confirmando que o VEGF165 parece conferir um efeito protetor no tratamento do infarto agudo do miocárdio. .

Fotocoagulación panretinal y bevacizumab intravítreo en el tratamiento de la retinopatía diabética proliferativa activa / Panretinal photocoagulation and intravitreal bevacizumab in the treatment of active proliferative diabetic retinopathy

OBJETIVO: evaluar el efecto de la fotocoagulación panretinal e inyección intravítrea de bevacizumab sobre las áreas de neovascularización en pacientes con retinopatía diabética proliferativa activa. MÉTODOs: estudio experimental en 80 ojos de 62 pacientes con retinopatía diabética proliferativa con características de alto riesgo, a quienes se les asignó aleatoriamente fotocoagulación panretinal (Grupo L) o fotocoagulación panretinal con bevacizumab intravítreo (Grupo L + B). Variables: edad, sexo, color de la piel, tipo de diabetes mellitus, tiempo de evolución, tipo de tratamiento, área de difusión de fluoresceína y regresión de neovascularización retinal y/o del disco óptico. Se realizó un seguimiento de 9 meses. RESULTADOS: en la evaluación inicial el área media de difusión fue de 8,95 mm2 en el grupo L y de 10,08 mm2 en el grupo L + B (p = 0,347), que se modificó a 6,40 mm2 y 3,91 mm2 (p = 0,012) al mes; 3,15 mm2 y 1,02 mm2(p = 0,002) a los tres meses; 2,45 mm2 y 0,58 mm2 (p = 0,001) a los seis meses; 2,18 mm2 y 0,46 mm2 (p = 0,001) a los nueve meses, respectivamente. El análisis de las diferencias absolutas de los promedios mostró una reducción significativa de las áreas de difusión a favor del tratamiento combinado en comparación con el momento inicial. CONCLUSIONES: en pacientes con retinopatía diabética proliferativa activa el bevacizumab intravítreo combinado con fotocoagulación panretinal produjo regresión dramática de la neovascularización, permaneciendo estable desde el tercer mes al noveno.

OBJECTIVE: to evaluate the effect of panretinal photocoagulation and intravitreal injection of bevacizumab on neovascularization areas of patients with active proliferative diabetic retinopathy. METHODS: experimental study conducted in 80 eyes from 62 patients with proliferative diabetic retinopathy with high risk characteristics. These patients were randomly assigned to panretinal photocoagulation group (group L) or to the panretinal photocoagulation plus intravitreal bevacizumab group (group L + B). The studied variables were age, sex, race, type of diabetes mellitus, illness duration, type of treatment, fluorescein distribution area and retinal/optical disc neovascularization regression area. They were followed-up for 9 months. RESULTS: in the initial evaluation, the average diffusion area was 8,95 mm2 in group L and 10,08 mm2 in group L + B (p = 0,347), which changed to 6,40 mm2 and 3,91 mm2 (p = 0,012) respectively, after one month; 3,15 mm2 and 1,02 mm2 (p = 0,002) three months later, 2,45 mm2 and 0,58 mm2 (p = 0,001) after six months and 2,18 mm2 and 0,46 mm2 (p = 0,001) after nine months, respectively. The analysis of absolute differences of averages showed a significant reduction in the distribution areas of fluorescein that favored the combined therapy. CONCLUSIONS: in patients with active proliferative diabetic retinopathy, intravitreal bevacizumab combined with panretinal photocoagulation bring about dramatic regression of neovascularization, which remained stable from the third to the ninth month.

Novel targeted agents for the treatment of bladder cancer: translating laboratory advances into clinical application: [review]

Bladder cancer is a common and frequently lethal cancer. Natural history studies indicate two distinct clinical and molecular entities corresponding to invasive and non-muscle invasive disease. The high frequency of recurrence of noninvasive bladder cancer and poor survival rate of invasive bladder cancer emphasizes the need for novel therapeutic approaches. These mechanisms of tumor development and promotion in bladder cancer are strongly associated with several growth factor pathways including the fibroblast, epidermal, and the vascular endothelial growth factor pathways. In this review, efforts to translate the growing body of basic science research of novel treatments into clinical applications will be explored.

Effects of therapeutic angiogenesis with plasmid VEGF165 on ventricular function in a canine model of chronic myocardial infarction / Efeito da angiogênese terapêutica com VEGF165 sobre a função ventricular em infarto do miocárdio crônico

OBJECTIVE: Therapeutic angiogenesis is currently under investigation in ischemic heart disease. We examined the effect on left ventricular function induced by therapeutic angiogenesis by intramyocardial injection of plasmid VEGF165, in a canine model of chronic myocardial infarction. METHODS: Left thoracotomy was performed in 10 mongrel dogs, and myocardial infarction induced by ligation of the major diagonal coronary artery. At 7 postoperative (p.o.) day (pre-treatment), left ventricular ejection fraction was assessed by echocardiogram, and a second procedure was done: saline or plasmid VEGF165 at 200 mg/mL was injected over 10 points of the ischemic areas of control or treated groups, respectively. Fourteen days later (post-treatment, day 21) a control echocardiogram was performed, the animals were sacrificed and histological examination was performed. RESULTS: Ejection fraction was maintained in the treated group: 52.45 + 15.1 percent on day 7 and 48.53 + 11.74 percent on day 21 (P=0.59), and tended to decrease in the control group, from 59.3 + 4 percent to 39.37 + 19.43 percent (P=0.04), although absolute values did not differ significantly between groups. Histological examination revealed a non significant increase in capillary vessels number in all areas in treated group. Paradoxically, arterioles were significantly less in number in all areas of treated dogs. CONCLUSION: Intramyocardial injection of plasmid VEGF165, in this canine model of chronic myocardial infarction, resulted in preservation of left ventricular ejection fraction, contrary to the control group where left ventricular ejection fraction showed continuous decline during the experiment. Histological examination, however, was unable to explain completely these results.

OBJETIVO: Angiogênese por terapia gênica é alternativa ainda experimental para revascularização miocárdica. Este estudo objetivou verificar a indução de angiogênese e melhora funcional miocárdica pela injeção transmural de plasmídeo contendo VEGF165 em áreas de infarto crônico do miocárdio. MÉTODOS: Em 10 cães anestesiados, por toracotomia lateral esquerda, foi induzido infarto agudo do miocárdio (IAM) por meio da ligadura do ramo diagonal principal da artéria coronária descendente anterior. Após 7 dias, realizado ecocardiograma para avaliação da fração de ejeção (FE) ventricular esquerda. Os animais foram divididos em dois grupos: Tratado (GT) e Controle (GC) e submetidos a segundo procedimento, para injeção intramiocárdica de solução contendo plasmídeo VEGF165 na concentração de 200mg/ml (GT) ou solução salina (GC), distribuída em 10 pontos da área infartada. Após 14 dias, novo ecocardiograma, sacrifício dos animais e retirada do coração para estudo histológico. RESULTADOS: Houve tendência à manutenção da FE no GT e de queda da FE no GC, conforme os valores: FE ao ecocardiograma pós-IAM inicial: GC 59,33 + 4,6 por cento e GT 52,45 + 15,1 por cento (P=0,359). FE após 14 dias: GC 39,37 + 19,43 por cento e GT 48,53 + 11,74 por cento (P=0,394). Comparação intra-grupo: Variação negativa da FEVE GC: 59,37 + 4 por cento para 39,37 + 19,43 por cento (P=0,04) e manutenção GT: 52,45 + 15,1 por cento para 48,53 + 11,74 por cento (P=0,59). No GT observou-se aumento do número de vasos capilares, mais intenso nas regiões injetadas, porém presente em todo miocárdio. Paradoxalmente, no GT houve redução do número de arteríolas. CONCLUSÃO: A injeção transmural de plasmídeo VEGF165 resultou em tendência para atenuar a perda de contratilidade consequente ao dano miocárdico, na fase crônica do IAM. O exame histológico da rede vascular, entretanto, não explica completamente os eventos funcionais.

Papel do fator de crescimento endotelial vascular nos carcinomas de tireóide / The role of vascular endothelial growth factor in tumor

O crescimento tumoral está diretamente relacionado com a neovascularização, a qual decorre do desequilíbrio entre os fatores pró-angiogênicos e antiangiogênicos, secretados pelas células neoplásicas. O fator de crescimento endotelial vascular (VEGF) desempenha papel chave na angiogênese tumoral, estimulando a proliferação, migração e sobrevivência das células endoteliais. Atua através da ligação a receptores tirosina quinase específicos: VEGFR-1/Flt-1, VEGFR-2/KDR e VEGFR-3. O aumento da expressão do VEGF e de seus receptores tem sido associado à progressão, metastatização e pior prognóstico em diversos tumores malignos. A compreensão das vias moleculares que envolvem o mecanismo de indução da angiogênese tumoral por fatores de crescimento como o VEGF aumentam as possibilidades de novas terapêuticas a serem utilizadas no tratamento de tumores malignos humanos. Evidências indicam um importante papel do VEGF nas neoplasias da tireóide e a utilização de inibidores do VEGF ou de seus receptores pode constituir um importante recurso terapêutico, já tendo sido utilizado em determinados tipos de tumores humanos. O presente artigo tem como objetivo fazer uma revisão da atuação do VEGF no crescimento tumoral com enfoque nas neoplasias malignas da tireóide.

The neoplasic process is directly related to neovascularization, an imbalance between pro-angiogenic and antiangiogenic factors. The vascular endothelial growth factor (VEGF) plays a key role in tumor angiogenesis, stimulating proliferation, migration and survival of endothelial cells. VEGF acts through binding to specific tyrosine kinase receptor: VEGFR-1/Flt-1, VEGFR-2/KDR and VEGFR-3. Increased expression of VEGF and its receptors have been associated with progression, metastasis and worse prognosis in human malignant tumors. Understanding molecular pathways of tumor angiogenesis related to growth factors such as VEGF is a crucial step on developing new treatment options. Evidence indicates an important role of VEGF in thyroid cancer and inhibition of VEGF or its receptors may constitute an important therapeutic resource, particularly for those patients with metastatic diseases. This aim of this article is to review the role of VEGF in tumor growth, focusing on thyroid malignancies.

Terapia angiogénica en el tratamiento de la cardiopatía isquémica / Angiogenic therapy in the ischemic cardiopathy treatment

Se realizó un recorrido por la historia del uso de los factores de crecimiento y se analizaron los conceptos de angiogénesis, arteriogénesis y vasculogénesis. Se señalaron los diferentes factores de crecimiento que se conocen y se hizo especial énfasis en los más utilizados (factor de crecimiento endotelial vascular y el factor de crecimiento fibroblástico). Se analizaron las diferentes vías de aplicación de estos, así como la forma de administración (proteica o génica). Realizamos un recuento de los diferentes estudios preclínicos y clínicos con el uso de estos factores de crecimiento para el tratamiento de la cardiopatía isquémica. De los diferentes estudios se recogieron las posibles complicaciones del uso de estos factores, llegamos a conclusiones y planteamos recomendaciones(AU)

The history of the use of growth factors and the concepts of angiogenesis, arteriogenesis and vasculogenesis were presented in this paper. The different growth factors that are known so far were stated, making emphasis on the most used (vascular endothelial and fibroblast growth factors). The various ways of application and of administration proteic or genic) were analyzed. An account of several preclinical and clinical studies using these growth factors for ischemic cardiopathy treatment were made. The various studies contributed information on the possible complications of the use of these factors; conclusions were drawn and recommendations were made(AU)

Intramyocardial gene transfer of vascular endothelial growth factor 121 improves myocardial perfusion and function in the ischemic porcine heart

Vascular endothelial growth factor (VEGF) is an endothelial cell-specific mitogen that is angiogenic in vitro and in vivo. Several studies report on gene transfer of VEGF121 to promote angiogenesis in the ischemic myocardium of animals and patients. We hypothesized that intramyocardial administration of naked plasmid DNA encoding VEGF121 could improve myocardial perfusion and function in a porcine model of myocardial ischemia. Yorkshire swine underwent thoracotomy and placement of an ameroid constrictor on the circumflex coronary artery. Four weeks later, pVEGF121 plasmid was administered into the ischemic myocardium. Four weeks after gene transfer, SPECT imaging demonstrated significant reduction in the ischemic area in pVEGF121-treated animals compared with controls. In the pVEGF121 group, most of the animals evolved from light ischemia to a normal perfusion. In contrast, control animals exhibited similar or impaired ischemic conditions. Our results indicate that intramyocardial gene transfer of VEGF121 as naked plasmid DNA results in significant improvement in myocardial perfusion and function.