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

Comparison with surgical and percutaneous intramyocardial gene delivery

Philip Raake, MD^*, Georges von Degenfeld, MD^*, Rabea Hinkel, DVM^*, Robert Vachenauer^*, Torleif Sandner^*, Sabrina Beller^*, Martin Andrees^*, Christian Kupatt, MD, PhD^*, Gerhard Schuler, PhD and Peter Boekstegers, PhD^*,*

^* Internal Medicine I, Grosshadern University Hospital, Munich, Germany
Department of Cardiology, Heart Center, University of Leipzig, Leipzig, Germany

View larger version (26K): [in a new window]   Figure 1 Harvesting of myocardial probes for measurement of regional myocardial beta-galactosidase concentration. After excision of the heart, the left ventricle (LV) was sliced parallel to the short axis from the apex to the basis. Each slice was divided into segments of equal size followed by dividing each segment into a epicardial (EPI), midmyocardial (MID), and subendocardial (ENDO) probe. RV = right ventricle.

View larger version (10K): [in a new window]   Figure 2 Mean transmyocardial beta-galactosidase expression in the left anterior descending coronary artery territory (open bars) and in the control, circumflex coronary artery area (solid bars) seven days after application of 5 x 109 pfu Ad2-CMV-beta-galactosidase. IMD = surgical intramyocardial delivery (group A); PIMD = percutaneous intramyocardial delivery (group B); retroinfusion = pressure-regulated retroinfusion of the anterior cardiac vein (group C). Mean ± SEM, n = 5/group. *p < 0.05 group C vs. group A and group B.

View larger version (19K): [in a new window]   Figure 3 Representative maps of the regional myocardial beta-galactosidase protein expression after catheter-based selective pressure-regulated retroinfusion of the anterior cardiac vein (retroinfusion), surgical intramyocardial direct injection (IMD), and percutaneous intramyocardial injection (PIMD). Each map represents one animal. ENDO = subendocardial probe; EPI = epicardial probe; MID = midmyocardial probe. Open bars = EPI; solid bars = MID; hatched bars = ENDO.

View larger version (17K): [in a new window]   Figure 4 Mean beta-galactosidase expression after adenoviral transfection in the epicardial (EPI), midmyocardial (MID), and subendocardial (ENDO) layers of the targeted left anterior descending coronary territory. Mean ± SEM, n = 5/group. **p < 0.05 group C vs. group A and group B; *p < 0.05 group C vs. group A; #p < 0.05 group A vs. group B; p < 0.05 group B vs. group A. Line with diamonds = retroinfusion; line with triangles = percutaneous intramyocardial delivery; line with squares = surgical intramyocardial delivery.

View larger version (100K): [in a new window]   Figure 5 Histochemical detection of beta-galactosidase seven days after adenoviral transfection by percutaneous intramyocardial delivery (A) and selective pressure-regulated retroinfusion of the adenoviral vectors into the coronary vein (B) (original magnification x 80).