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Eur J Cardiothorac Surg 2003;23:74-80
© 2003 Elsevier Science NL

Transmyocardial laser revascularization combined with vascular endothelial growth factor₁₂₁ (VEGF₁₂₁) gene therapy for chronic myocardial ischemia – do the effects really add up?

^a Department of Cardiovascular Surgery, Albert-Ludwigs-University Freiburg, Hugstetter Strasse 55, 79106 Freiburg, Germany
^b Institute of Pathology, Albert-Ludwigs-University Freiburg, Freiburg, Germany
^c Institute for Molecular Medicine, Albert-Ludwigs-University Freiburg, Freiburg, Germany

Received 5 February 2002; received in revised form 16 September 2002; accepted 21 October 2002.

* Corresponding author. Tel.: +49-761-270-2818; fax: +49-761-270-2550
e-mail: lutter{at}ch11.ukl.uni-freiburg.de

Objective: Different therapy strategies for coronary disease in conventionally untreatable patients have been developed, among them transmyocardial laser revascularization (TMLR) and the application of growth factors. The objective of our study was to determine whether a combined therapy of TMLR with a vascular endothelial growth factor₁₂₁ (VEGF₁₂₁) plasmid is able to stimulate the development of sufficient collateral circulation and hereby to preserve cardiac function. Materials and methods: A severe stenosis of the left anterior descending artery was created in healthy pigs. After 1 week, perfusion and regional contractility were assessed at baseline. Afterwards, the ischemic area was treated with TMLR (n=8), intramyocardial injection of naked plasmid DNA encoding VEGF₁₂₁ (n=7), or both (n=7). Control animals were left untreated (n=8). After 3 months, the animals were re-examined and underwent immunohistological analysis. Results: The number of capillaries increased only after injection of VEGF₁₂₁ plasmid alone compared to untreated ischemia and to the other therapy groups, whereas the number of arterioles was higher following TMLR treatment alone or in combination with VEGF₁₂₁ than it was in the case in untreated ischemic animals. However, only combined VEGF₁₂₁+TLMR therapy resulted in an improvement in regional myocardial blood flow in comparison with 1 week ischemia, indicating the efficient development of collateral circulation. In contrast, better regional contractility compared to the 1-week baseline, as well as restoration of the pre-ischemic values, were achieved by both VEGF₁₂₁ and combined VEGF₁₂₁+TLMR therapies. Conclusions: This study of chronic myocardial ischemia with a porcine model indicates a synergistic action of TMLR and VEGF₁₂₁ gene therapy. Combined treatment alone achieved an increase of regional myocardial perfusion, which accompanied arteriogenesis and corresponded with the restoration of regional function.

Key Words: Transmyocardial laser revascularization • Vascular endothelial growth factor₁₂₁ • Chronic myocardial ischemia

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