ABSTRACT
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.
Subject(s)
Animals , Collateral Circulation , Collateral Circulation/genetics , Vascular Endothelial Growth Factor A/pharmacology , Myocardial Ischemia/therapy , Genetic Therapy/methods , Analysis of Variance , Heart , Disease Models, Animal , DNA , Vascular Endothelial Growth Factor A/genetics , Vascular Endothelial Growth Factor A/therapeutic use , Gene Transfer Techniques , Myocardial Ischemia/physiopathology , Myocardial Ischemia/genetics , Plasmids/pharmacology , Myocardial Revascularization/methods , Swine , Coronary VesselsABSTRACT
The time-course of pancreatic lipid peroxidation and reduced glutathione, and blood glucose were studied in adult male CD-1 mice after each of three sequential injection of alloxan, administered at intervals of 48 h. Twenty four hours after alloxan administration an increment of blood glucose and pancreatic lipoperoxidation was observed. Lipoperoxication partially recovered, while blood glucose was increased after the third administration to a value of 150 mg/100 ml. Pancreas reduced glutathione content remained without any significant change throughout the experiment. These results suggest that the stablishment of alloxan-induced diabetes is proceded by an increment in pancreatic lipid peroxidation that could be associated with permanent damage to pancreatic tissue