Accelerated intimal hyperplasia in aortocoronary internal mammary vein grafts in minipigs.
BACKGROUND
More than 50% of aortocoronary saphenous vein grafts are occluded 10 years after surgery. Intimal hyperplasia is the initial critical step in the progression toward occlusion. Internal mammary veins, which are physiologically prone to less hydrostatic pressure, may undergo an accelerated progression to intimal hyperplasia and thus be suitable for investigation of the mechanisms of aortocoronary vein graft disease.


METHODS
Six minipigs underwent aortocoronary bypass grafting using standard cardiopulmonary bypass and cardioplegic arrest. Mammary vein were grafted in a reversed manner from ascending aorta to left anterior descending coronary artery (LAD). The proximal LAD was ligated, rendering the anterior left ventricle vein graft-dependent. Minipigs were killed after 4 weeks, and vein grafts were harvested. Histological and immunohistological investigation were performed with respect to morphometric analysis, endothelial damage/dysfunction (v-Willebrand-factor (vWF)), smooth muscle cells (alpha-smooth actin) and proliferation rate (proliferation marker Ki 67).


RESULTS
Mean intimal area of vein grafts was increased compared to ungrafted mammary veins. Intimal hyperplasia in vein grafts was characterized by massive accumulation of smooth muscle cells with a high proliferation rate and endothelial perturbation. Significant (p = 0.001) intimal hyperplasia of the grafted mammary vein compared to the ungrafted mammary vein was found. These changes were absent in ungrafted mammary veins.


CONCLUSIONS
The present study demonstrates a pig model of aortocoronary vein graft intimal hyperplasia which is characterized by an accelerated progression within internal mammary veins. The model is suitable to investigate the pathophysiology of aortocoronary vein graft intimal hyperplasia as well as therapeutic approaches.
Popov
Aron Frederik
AF
Department of Thoracic Cardiovascular Surgery, University of Göttingen, Germany. Popov@med.uni-goettingen.de
Dorge
Hilmar
H
Hinz
Jose
J
Schmitto
Jan Dieter
JD
Stojanovic
Tomislav
T
Seipelt
Ralf
R
Didilis
Vassilios
V
Schoendube
Friedrich Albert
FA
D000818:Animals; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D004195:Disease Models, Animal; D005260:Female; D006965:Hyperplasia / Q000473:pathology; D008321:Mammary Glands, Animal / Q000098:blood supply*; D017202:Myocardial Ischemia / Q000601:surgery*; D011183:Postoperative Complications; D013350:Subclavian Vein / Q000637:transplantation*; D013552:Swine; D013556:Swine, Miniature; D016896:Treatment Outcome; D017539:Tunica Intima / Q000473:pathology*