Long-term endothelial dysfunction is more pronounced after stenting than after balloon angioplasty in porcine coronary arteries
Heleen M. M. van Beusekom, PhD* b,
Deirdre M. Whelan, BSc* b,
Sjoerd H. Hofma, MD* b,
Stefan C. Krabbendam, BSc* b,
Victor W. M. van Hinsbergh, PhD*  b,d,
Pieter D. Verdouw, PhD* b and
Willem J. van der Giessen, MD, PhD* b
* Experimental Cardiology, Thoraxcenter, Cardiovascular Research Institute COEUR, Erasmus University Rotterdam, Rotterdam, The Netherlands
b Interuniversity Cardiology Institute ICIN, Rotterdam, The Netherlands
Gaubius Laboratory TNO-PG, Leiden, The Netherlands
d Institute for Cardiovascular Research, Free University, Amsterdam, The Netherlands
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Figure 1 EB can be administered both intravenously and intracoronarily. Intravenous administration results in the spontaneous binding of EB to albumin, and subjection of the arterial wall to the 70-kD large complex. Intracoronary administration after a saline flush to remove serum proteins results in subjection of the arterial wall to the smaller 1-kD molecule. Blue staining of the arterial wall indicates a breach in the luminal barrier.
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Figure 2 Macroscopy of the dye-exclusion test. A, Control right coronary artery, shows a clean surface with occasional small blue areas. B, Group 2, Palmaz-Schatz stent, 1 kD. For both molecular weights, blue staining is found mainly at the stent ends and in the area of the coupler (arrows). C, Group 3A Wiktor stent. Blue staining is seen especially in the region of the intimal tissue covering the stent struts (arrows). D, Group 3B, PTCA. Randomly stained areas (arrows) are found in the arterial segment treated with PTCA and are more apparent and intense in group 3B than 4B.
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Figure 3 EM of groups 3 and 4. A, Scanning EM of a nonblue area showing normal endothelium. B, Endothelial cell retraction at 2 weeks after stenting as illustrated by scanning EM, shows fingerlike projections between adjacent endothelial cells (arrowhead). Some have broken during critical point drying (asterisk). C, Transmission EM at 2 weeks after stenting shows loose junctions (arrow) between adjacent endothelial cells. D, At 12 weeks after stenting, transmission EM shows tight junctions (arrow). E, The permeable areas in the endothelium at 12 weeks after stenting are characterized by surface folds as observed with transmission EM (arrow). N = nucleus.
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Figure 4 LM. A, Group 3B. At 2 weeks after PTCA, focal lesions can be found with BrdU incorporation (arrow), especially underneath the endothelial lining but also elsewhere in the intima (i) and media (m). HRP-DAB with hematoxylin counterstain. Bar = 50 µm. B, Group 4B. At 12 weeks after PTCA, there is still a limited NI, sometimes with an additional elastic membrane underneath the endothelium (arrow). Resorcin-Fuchsin, i = intima, m = media. Bar = 50 µm.
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Figure 5 Macroscopy c-AMP–treated arteries. Macroscopy of the coronary arteries at 2 weeks after implantation of a Wiktor stent. While a "control" artery (A) was not exposed to db-c-AMP, but only to EB, the c-AMP-treated artery was first exposed to 1 mM db-c-AMP and then to EB with a molecular weight of 1 kD (B), showing an improvement especially in the areas between the stent struts.
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