Mechanisms of late lumen loss after antiproliferative percutaneous coronary intervention using beta-irradiation in a porcine model of restenosis.
BACKGROUND
The short-term results for the prevention of coronary restenosis after intravascular brachytherapy (IVBT) and use of drug-eluting stents (DESs) are excellent. The long-term results either lack or present with late complications (e.g., late thrombosis and late catch-up phenomenon leading to late restenosis even years after the initial procedure). Both IVBT and DESs mediate their potent antirestenotic effects via a cytostatic mechanism, but the cardiovascular pathology at late time points after the use of these antiproliferative therapies is incompletely understood. This study investigated the long-term effects of antiproliferative beta-irradiation in a clinically relevant porcine coronary model to address the pathophysiology of late coronary restenosis after antiproliferative vascular interventions.


METHODS
We performed percutaneous transluminal coronary angioplasty (PTCA) in two major coronary arteries in 12 domestic crossbred pigs. One of the two balloon-injured segments was randomly assigned to receive immediate beta-irradiation (PTCA+IVBT group) using a noncentered delivery catheter (20 Gy; Novoste Beta-Cath System, Novoste, Norcross, GA, USA). The animals were sacrificed after 14 days (n=6) or 3 months (n=6).


RESULTS
The luminal area in the PTCA+IVBT group decreased significantly 3 months after the intervention as compared with that in the PTCA group (PTCA 3.45+/-0.46 mm2 vs. PTCA+IVBT 1.22+/-0.26 mm2; P=.0017). This lumen loss was primarily due to shrinkage of the external elastic lamina area (negative arterial remodeling; PTCA 5.22+/-0.27 mm2 vs. PTCA+IVBT 3.42+/-0.45 mm2; P=.0064), which was accompanied by an increase in the adventitial area (PTCA 3.07+/-0.2 mm2 vs. PTCA+IVBT 5.41+/-0.5 mm2; P=.0049).


CONCLUSIONS
The application of antiproliferative radiation in a porcine coronary model caused an early beneficial effect (reduction of intimal-medial lesion and luminal gain) that was followed by a late lumen loss primarily due to negative arterial remodeling. This mechanism may in part help us understand the pathophysiology of late adverse events occurring after IVBT.
Deiner
Carolin
C
Department of Cardiology, Charité-Campus Benjamin Franklin, Berlin, Germany.
Loddenkemper
Christoph
C
Rauch
Ursula
U
Rosenthal
Peter
P
Pauschinger
Matthias
M
Schwimmbeck
Peter L
PL
Schultheiss
Heinz-Peter
HP
Pels
Klaus
K
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D001610:Beta Particles; D001918:Brachytherapy / Q000009:adverse effects* / Q000379:methods; D049109:Cell Proliferation / Q000528:radiation effects*; D003238:Connective Tissue / Q000473:pathology / Q000528:radiation effects; D023903:Coronary Restenosis / Q000209:etiology / Q000473:pathology / Q000532:radiotherapy*; D003331:Coronary Vessels / Q000293:injuries / Q000473:pathology / Q000528:radiation effects*; D004195:Disease Models, Animal; D004547:Elastic Tissue / Q000473:pathology / Q000528:radiation effects; D012107:Research Design; D034421:Sus scrofa; D013997:Time Factors; D017539:Tunica Intima / Q000293:injuries / Q000473:pathology / Q000528:radiation effects*; D017540:Tunica Media / Q000293:injuries / Q000473:pathology / Q000528:radiation effects*