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Eur J Cardiothorac Surg 2001;20:1128-1134
© 2001 Elsevier Science NL

Simultaneous surgical revascularization and angiogenic gene therapy in diffuse coronary artery disease

^a Department of Cardiothoracic Surgery, Völklingen Heart Centre, Richardstrasse D-66333, Volklingen/Saar, Germany
^b Institute of Human Genetics, University of Saarland, Homburg/Saar, Germany
^c Department of Cardiology, Völklingen Heart Centre, Richardstrasse D-66333, Volklingen/Saar, Germany

Received 28 March 2001; received in revised form 5 September 2001; accepted 5 September 2001.

Corresponding author. Tel.: +49-6898-12-2473; fax: +49-6898-12-2258
e-mail: huwer.vk{at}shg-kliniken.de

Objective: The cytokine vascular endothelial growth factor (VEGF) is capable of triggering angiogenesis and at higher concentrations vasculogenesis. We report on a pilot study where VEGF-DNA as an additional therapy to coronary artery bypass grafting was injected into the myocardium in 24 patients (pts) with proximal coronary artery stenosis and diffuse peripheral disease. One region of the myocardium with proven ischemia remained unsupplied after surgery because the respective epicardial coronary artery was not graftable. Methods and results: Plasmid DNA encoding for the 165- and 167-amino acid isoform of the human VEGF genes was injected directly into the myocardium, not amenable to surgical revascularization at a dosage of 1000 µg each, using a standardized protocol. A^99mTc-sestamibi-SPECT at rest performed 7 days prior to the operation, had shown decreased marker activity in the region of interest. Controls were made 1 week and 80–100 days postoperatively. Transmural scaring was ruled out intraoperatively. Coronary and left ventricular angiographies were performed preoperatively and 3 months postsurgery, respectively. One or more of the following angiographic items were found in 16/24 patients postoperatively. (1) Improvement of regional left ventricular function at the VEGF treated myocardial sector (5/24 pts). (2) Newly visible vessels considered as collaterals (8/24 pts). (3) Earlier filling of parent vessels (6/24 pts). (4) An increase in diameter of preoperatively existing collateral vessels (7/24). An increased perfusion at rest in the region of gene application was detected in 3/24 patients by early postoperative ^99mTc-sestamibi-SPECT investigation. In six additional cases, local perfusion increased markedly until the late examination. No perioperative myocardial infarctions and no signs of inflammation were observed. Newly developed abnormal vasculature was not detected in any patient. Conclusions: Direct intramyocardial administration of VEGF₁₆₅-DNA and VEGF₁₆₇-DNA may result occasionally in an enhancement of collateral vascularization in regions with diffuse peripheral coronary artery disease not surgically amenable. During midterm follow-up no adverse effects of VEGF-DNA application are observed so far. The very slight midterm improvements caused us to stop further VEGF-DNA application and, in our opinion, do not justify a prospective, and randomized study with a control group.

Key Words: Coronary disease • Bypass grafting • Gene therapy • Angiogenesis • Collateral revascularization

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