Intrapericardial ethanol delivery inhibits neointimal proliferation after porcine coronary overstretch.
BACKGROUND
Previous work has shown that ethanol dampens cell growth signals and inhibits smooth muscle proliferation in a restenosis model. Catheter-based approaches to intrapericardial (IPC) delivery of therapeutic agents have been recently demonstrated to be feasible. This study tested the effect of IPC instillation of ethanol on the injury response of overstretched porcine coronary arteries.


METHODS
Ethanol, 30%, (E, 10 mL, n = 6) or saline, 0.9%, (C, 10 mL, n = 6) was administered IPC after overstretch injury of porcine coronary arteries. Animals were sacrificed 28 days after balloon dilation.


RESULTS
The neointimal and adventitial area were significantly reduced in the E group (0.36 +/- 0.05 mm2; 1.68 +/- 0.09 mm2) as compared to the C group (0.61 +/- 0.05 mm2; 2.61 +/- 0.14 mm2; p < 0.001). The maximal intimal and adventitial thicknesses of the treated vessels were also significantly smaller than those of untreated vessels (0.44 +/- 0.02, 0.38 +/- 0.08 mm vs 0.57 +/- 0.03, 0.54 +/- 0.03 mm, respectively; p < 0.005). The calculated luminal stenosis decreased in the treated group, 16.1%, versus the control group, 25.3%.


CONCLUSIONS
Perivascular administration of a single-dose of ethanol significantly reduce neointimal proliferation in the porcine balloon-overstretch model. This data suggests that intrapericardial delivery of therapeutic agents may be useful and feasible in the coronary angioplasty setting for prevention of restenosis.
Hou
Dongming
D
Indiana Center for Vascular Biology and Medicine, Indiana University School of Medicine, Indianapolis 46202, USA. dmhou@iupui.edu
Zhang
Ping
P
Marsh
Alexander E
AE
March
Keith L
KL
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology* / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage*; D005260:Female; D010496:Pericardium; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D000431:Ethanol