BASIC SCIENCE STUDIES
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
Georges von Degenfeld, MD*,
Philip Raake, MD*,
Christian Kupatt, MD*,
Corinna Lebherz, MD*,
Rabea Hinkel*,
Franz Josef Gildehaus, PhD ,
Wolfgang Münzing, PhD,
Andrea Kranz, PhD ,
Johannes Waltenberger, MD,
Marcus Simoes, MD ,
Markus Schwaiger, MD,
Eckart Thein, MD|| and
Peter Boekstegers, MD*,*
* Internal Medicine I, Grosshadern, Grosshadern University Hospital, Munich, Germany
Nuclear Medicine, Grosshadern University Hospital, Munich, Germany
Internal Medicine II, University Hospital, Ulm, Germany
Institute of Nuclear Medicine, Klinikum rechts der Isar, Munich, Germany
|| Institute of Surgical Research, Munich, Germany
* Reprint requests and correspondence: Prof. Dr. med. Peter Boekstegers, Medizinische Klinik I, Klinikum Grosshadern, Marchioninistr. 15, D-81377 München, Germany.
boekstegers{at}med1.med.uni-muenchen.de
OBJECTIVES: We sought to improve regional myocardial delivery and subsequent collateral perfusion induced by basic fibroblast growth factor-2 (FGF-2) using selective pressure-regulated retroinfusion of coronary veins for delivery. This hypothesis was tested in a newly developed pig model with percutaneous induction of chronic ischemia.
BACKGROUND: Selective pressure-regulated retroinfusion of coronary veins is a catheter-based procedure that has been shown to provide effective regional delivery of drugs and gene vectors into ischemic myocardium.
METHODS: A high-grade stenosis with subsequent progression to total occlusion within 28 days was induced by implanting a reduction stent graft into the left anterior descending artery (LAD). After seven days, a 30-min retroinfusion (anterior cardiac vein) was performed with (n = 7) or without (n = 7) 150 µg FGF-2 and compared with a 30-min antegrade infusion of 150 µg FGF-2 into the LAD (n = 7). Sonomicrometry to assess regional myocardial function at rest and during pacing, and microspheres to assess regional myocardial blood flow, were performed 28 days after implantation of the reduction stent.
RESULTS: Retroinfusion of FGF-2 compared favorably with controls and with antegrade infusion of FGF-2 with regard to regional myocardial function at rest (18.5 ± 4.1% vs. 5.7 ± 2.9% vs. 7.9 ± 1.8%, respectively, p < 0.05) and during pacing. Regional myocardial blood flow was also higher in the LAD territory after retroinfusion of FGF-2 (1.07 ± 0.14 vs. 0.66 ± 0.07 vs. 0.72 ± 0.17 ml·min–1·g–1, p < 0.05).
CONCLUSIONS: 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.
|
Abbreviations and Acronyms
| | CX | = circumflex artery | | FDG | = fluorodeoxyglucose | | FGF-2 | = fibroblast growth factor-2 | | LAD | = left anterior descending artery | | LV | = left ventricle/ventricular | | MI | = myocardial infarction | | PET | = positron emission tomography | | VEGF | = vascular endothelial growth factor |
|
This article has been cited by other articles:
|
|
|
|
 
C. Kupatt, R. Hinkel, M.-L. von Bruhl, T. Pohl, J. Horstkotte, P. Raake, C. El Aouni, E. Thein, S. Dimmeler, O. Feron, et al.
Endothelial Nitric Oxide Synthase Overexpression Provides a Functionally Relevant Angiogenic Switch in Hibernating Pig Myocardium
J. Am. Coll. Cardiol.,
April 10, 2007;
49(14):
1575 - 1584.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. von Degenfeld, A. Banfi, M. L. Springer, R. A. Wagner, J. Jacobi, C. R. Ozawa, M. J. Merchant, J. P. Cooke, and H. M. Blau
Microenvironmental VEGF distribution is critical for stable and functional vessel growth in ischemia
FASEB J,
December 1, 2006;
20(14):
2657 - 2659.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Madonna, L. Rinaldi, C. Rossi, Y.-J. Geng, and R. De Caterina
Prostacyclin improves transcoronary myocardial delivery of adipose tissue-derived stromal cells
Eur. Heart J.,
September 1, 2006;
27(17):
2054 - 2061.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Fukushima, S. R. Coppen, A. Varela-Carver, G. Brindley, K. Yamahara, P. Sarathchandra, M. H. Yacoub, and K. Suzuki
Enhanced efficiency of superoxide dismutase-induced cardioprotection by retrograde intracoronary administration
Cardiovasc Res,
February 1, 2006;
69(2):
459 - 465.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Raake, R. Hinkel, C. Kupatt, M.-L. v. Bruhl, S. Beller, M. Andrees, C. Vicol, and P. Boekstegers
Percutaneous approach to a stent-based ventricle to coronary vein bypass (venous VPASSTM): comparison to catheter-based selective pressure-regulated retro-infusion of the coronary vein
Eur. Heart J.,
June 2, 2005;
26(12):
1228 - 1234.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Cao, A. Hong, H. Schulten, and M. J. Post
Update on therapeutic neovascularization
Cardiovasc Res,
February 15, 2005;
65(3):
639 - 648.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Suzuki, B. Murtuza, S. Fukushima, R. T. Smolenski, A. Varela-Carver, S. R. Coppen, and M. H. Yacoub
Targeted Cell Delivery Into Infarcted Rat Hearts by Retrograde Intracoronary Infusion: Distribution, Dynamics, and Influence on Cardiac Function
Circulation,
September 14, 2004;
110(11_suppl_1):
II-225 - II-230.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Raake, G. von Degenfeld, R. Hinkel, R. Vachenauer, T. Sandner, S. Beller, M. Andrees, C. Kupatt, G. Schuler, and P. Boekstegers
Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins: Comparison with surgical and percutaneous intramyocardial gene delivery
J. Am. Coll. Cardiol.,
September 1, 2004;
44(5):
1124 - 1129.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
