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1.
Clin Sci (Lond) ; 112(4): 241-50, 2007 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-16989643

RESUMEN

Therapies aimed at enhancing cardiomyocyte survival following myocardial injury are urgently required. As GHRP6 [GH (growth hormone)-releasing peptide 6] has been shown to stimulate GH secretion and has beneficial cardiovascular effects, the aim of the present study was to determine whether GHRP6 administration reduces myocardial infarct size following acute coronary occlusion in vivo. Female Cuban Creole pigs were anaesthetized, monitored and instrumented to ensure a complete sudden left circumflex artery occlusion for 1 h, followed by a 72 h reperfusion/survival period. Animals were screened clinically before surgery and assigned randomly to receive either GHRP6 (400 microg/kg of body weight) or normal saline. Hearts were processed, and the area at risk and the infarct size were determined. CK-MB (creatine kinase MB) and CRP (C-reactive protein) levels and pathological Q-wave-affected leads were analysed and compared. Evaluation of the myocardial effect of GHRP6 also included quantitative histopathology, local IGF-I (insulin-growth factor-I) expression and oxidative stress markers. GHRP6 treatment did not have any influence on mortality during surgery associated with rhythm and conductance disturbances during ischaemia. Infarct mass and thickness were reduced by 78% and 50% respectively, by GHRP6 compared with saline (P<0.01). More than 50% of the GHRP6-treated pigs did not exhibit pathogological Q waves in any of the ECG leads. Quantitative histopathology and CK-MB and CRP serum levels confirmed the reduction in GHRP6-mediated necrosis (all P<0.05). Levels of oxidative stress markers suggested that GHRP6 prevented myocardial injury via a decrease in reactive oxygen species and by the preservation of antioxidant defence systems (all P<0.05). Myocardial IGF-I transcription was not amplified by GHRP6 treatment compared with the increase induced by the ischaemic episode in relation to expression in intact hearts (P<0.01). In conclusion, GHRP6 exhibits antioxidant effects which may partially contribute to reduce myocardial ischaemic damage.


Asunto(s)
Antioxidantes/uso terapéutico , Cardiotónicos/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Miocitos Cardíacos/efectos de los fármacos , Oligopéptidos/uso terapéutico , Animales , Arritmias Cardíacas/prevención & control , Proteína C-Reactiva/metabolismo , Supervivencia Celular/efectos de los fármacos , Forma MB de la Creatina-Quinasa/sangre , Modelos Animales de Enfermedad , Electrocardiografía/efectos de los fármacos , Femenino , Factor I del Crecimiento Similar a la Insulina/metabolismo , Infarto del Miocardio/metabolismo , Infarto del Miocardio/patología , Miocardio/patología , Miocitos Cardíacos/patología , Necrosis/prevención & control , Tamaño de los Órganos/efectos de los fármacos , Oxidación-Reducción , Estrés Oxidativo/efectos de los fármacos , Porcinos
2.
Electron. j. biotechnol ; Electron. j. biotechnol;7(3): 08-09, Dec. 2004. ilus, graf, tab
Artículo en Inglés | LILACS | ID: lil-448765

RESUMEN

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.


Asunto(s)
Animales , Circulación Colateral , Circulación Colateral/genética , Factor A de Crecimiento Endotelial Vascular/farmacología , Isquemia Miocárdica/terapia , Terapia Genética/métodos , Análisis de Varianza , Corazón , Modelos Animales de Enfermedad , ADN , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/uso terapéutico , Técnicas de Transferencia de Gen , Isquemia Miocárdica/fisiopatología , Isquemia Miocárdica/genética , Plásmidos/farmacología , Revascularización Miocárdica/métodos , Porcinos , Vasos Coronarios
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