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EXPERIMENTAL STUDY

Endoluminal reconstruction of the arterial wall with endothelial cell/glue matrix reduces restenosis in an atherosclerotic rabbit

Nicholas Kipshidze, MD, PhD, FACC^¶, James J. Ferguson, III, MD, FACC, Michael H. Keelan, Jr., MD, FACC^*, Harry Sahota, MD, Richard Komorowski, MD^*, Latha Raja Shankar, MD^*, Paramjith S. Chawla, MD^*, Christian C. Haudenschild, MD^||, Victor Nikolaychik, MD and Jeffrey W. Moses, MD, FACC^¶

^* Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Milwaukee Heart Project, Milwaukee, Wisconsin, USA
Good Samaritan Hospital, Los Angeles, California, USA
Texas Heart Institute, Houston, Texas, USA
^|| JH Holland Laboratory, American Red Cross, Rockville, Maryland, USA
^¶ Lenox Hill Heart and Vascular Institute of New York, and Cardiovascular Research Foundation, New York, New York, USA

Manuscript received July 30, 1998; revised manuscript received March 17, 2000, accepted May 4, 2000.

Reprint requests and correspondence: Dr. Nicholas Kipshidze, Lenox Hill Heart and Vascular Institute of New York, Lenox Hill Hospital, 130 East 77th Street, New York, New York 10020
nkipshidze{at}lenoxhill.net

OBJECTIVES

The objectives of this study were 1) to improve the attachment of reimplanted endothelial cells (EC) using a fibrin glue, and 2) to assess the impact of endothelial reseeding on restenosis eight weeks after balloon angioplasty.

BACKGROUND

A possible mechanism contributing to restenosis after balloon angioplasty is the loss of the EC lining. Previous attempts to reseed EC had little effect due to rapid loss of the seeded cells.

METHODS

Twelve atherosclerotic rabbits were subjected to angioplasty of iliac arteries and reseeding procedure. One iliac artery was subjected to EC/glue reconstruction and a contralateral site to EC seeding without glue. The animals were sacrificed after 4 h. In another series 12 rabbits were treated in the same fashion and were restudied at eight weeks. Additionally, in 10 animals one iliac was subjected to glue treatment, and another served as control.

RESULTS

Histological examination demonstrated the ability of this method to reattach the EC/glue matrix circumferentially to 68.0 ± 6.7% of the arterial wall in comparison with 13.5 ± 3.9% reattachment after EC seeding. Morphometry at eight weeks showed that the lumen area was significantly greater in the EC/glue group (1.23 ± 0.35 mm²) than in the EC seeding alone (0.65 ± 0.02 mm²) and 0.72 ± 0.41 mm² in the glue group. This was principally accounted for by the statistically significant differences in the intimal area (0.76 ± 0.18 mm² vs. 1.25 ± 0.26 mm² and 1.01 ± 0.53 mm², respectively).

CONCLUSIONS

The attachment of EC after angioplasty can be greatly improved with fibrin glue matrix. The near 70% endothelial coverage achieved by this method resulted in a significant reduction of restenosis in atherosclerotic rabbit.

Abbreviations and Acronyms   DMEM = Dulbecco’s modified Eagle’s medium   EC = endothelial cell   MLD = minimal luminal diameter   PTCA = percutaneous transluminal coronary angioplasty   VPF = vascular permeability factor

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