Selective Pressure-Regulated Retroinfusion for Gene Therapy Application in Ischemic Heart Disease

Abstract

Coronary heart disease is still the leading cause of death in industrialized nations. Even though revascularization strategies such as coronary artery bypass graft surgery, percutaneous coronary intervention and enhanced drug therapy significantly improved the outcome, about 30 % of patients develop chronic heart failure. Ischemic heart disease and heart failure are characterized by an adverse remodeling of the heart, featuring cardiomyocyte hypertrophy, increased fibrosis and capillary rarefaction. Therefore, gene therapeutic approaches for the treatment of heart failure, such as the modulating contractile function or therapeutic neovascularization, seem to be promising. To achieve an efficient transduction of the gene therapeutic agent, the time point and the application route seem to be important for the therapeutic success. In contrast to the classical systemic application regional intra-coronary application offers the possibility of higher transduction efficacy in the target area accompanied by a reduced off-target contamination. Antegrade delivery however, may be impaired by coronary heart disease, such as stenosis or occlusion of a coronary artery. Coronary veins appear not to be affected and might therefore be the preferable application route for gene therapy. For an effective and safe retrograde application in gene therapy, selective catheterization of the coronary vein draining the target area is necessary. In addition, to avoid coronary vein injury, a pressure regulated infusion enhances safety. Therefore, a selective pressure regulation of retroinfusion (SSR) seems to be a favorable approach for gene therapy transduction in combination with reduced systemic contamination.