Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins

Abstract

Percutaneous selective pressure-regulated retroinfusion compares favorably with surgical and percutaneous intramyocardial injection techniques by providing a more homogenous and even more efficient adenoviral gene delivery.

Cardio-specific long-term gene expression in a porcine model after selective pressure-regulated retroinfusion of adeno-associated viral (AAV) vectors

“…30,34 Selective pressure-regulated retroinfusion of the coronary veins prolongs adhesion time of the vector with the cardiac endothelium and increases endothelial permeability. 14,19 The increased transduction efficiency in the VEGF approach might be explained by an additional increase in vascular permeability as observed previously in systemic transduction of mice with AAV vectors or intracoronary transfer in rabbits using adenoviral vectors. 23,30 We have used AAV vectors since they enable a longterm gene expression in the heart in the absence of an immune or inflammatory reaction in small animal models.…”

“…14,19,41,42 Catheter introducer sheaths were placed in the right carotid artery and right external jugular vein. Full anticoagulation was achieved by bolus injection of heparin 10 000 IU followed by continuous application of 5000 IU h…”

“…It has been previously demonstrated that transvascular (intracoronary or retrograde coronary venous) application of vectors for gene therapy is feasible. [1][2][3][4][5][6][7][8][9][10][11][12][13][14] We have chosen pressure-regulated retroinfusion of the coronary veins, as a catheterbased delivery system, which has been previously proven to be safe for human application. 15,16 Recently, it has been shown to provide efficient gene transfer to ischemic and nonischemic myocardium.…”

Percutaneous methods of vector delivery in preclinical models

“…16 In combination with a specialized device for pressure regulation this approach also demonstrated an increased transfection efficacy compared with antegrade injection. 17 However, there are limitations by the pressure coming from the physiological antegrade flow. In a comparison study of different injection techniques by Hoshino et al 11 retrograde injected microspheres were rather distributed in scattered pattern (Figure 2b).…”

“…Although even with this technique overall distribution is limited. 17 This fact limits the use of this method in a patient setting, making this a significantly more invasive approach and diminishing the described advantages.…”