Selective Pressure-Regulated retroinfusion of fibroblast growth factor-2 into the coronary vein enhances regional myocardial blood flow and function in pigs with chronic myocardial ischemia

Abstract

Selective pressure-regulated retroinfusion increased tissue binding of FGF-2 and enhanced functionally relevant collateral perfusion compared with antegrade intracoronary delivery in pigs with chronic myocardial ischemia.

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.…”

“…Combination of selective retroinfusion into the anterior interventricular vein with AAV vectors resulted in a significant luciferase reporter gene expression in the LAD target area, but not the LCX nontarget area after 4 weeks. We have chosen selective retroinfusion since this percutaneous technique is superior to intracoronary antegrade delivery of angiogenic proteins 19 and adenoviral vectors 13 and results in a more homogenous gene transfer than intramyocardial injections. 14 A major limitation of intracoronary infusion is the short adhesion time of the vector with the coronary endothelium.…”

“…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…”

“…This was demonstrated in case of cDNA transfer of vascular endothelial growth factor (VEGF) and heat shock protein 90 in a chronic porcine ischemia/reperfusion model. 17,18 With regard to application of an angiogenic protein (fibroblast growth factor-2) 19 and adenoviral gene transfer, 13 pressure-regulated retroinfusion was superior to intracoronary antegrade delivery. Furthermore, a 'head to head' comparison with percutaneous and surgical intramyocardial injection highlighted the more efficient and much more homogenous gene transfer by pressureregulated retroinfusion.…”

“…For selective retroinfusion, the anterior interventricular vein was catheterized using a 6F retroinfusion catheter. [13][14][15]17,19,[41][42][43] In all animals a 7F guiding catheter was placed in the left coronary artery and the LAD was wired. During retrograde delivery of the AAV vectors, the LAD artery was occluded by a PTCA balloon distal to the first diagonal branch in all groups.…”