A new single-injury model of balloon angioplasty in cholesterol-fed rabbits: beneficial effect of hirudin and comparison with double-injury model.
Air desiccation endothelial injury followed by cholesterol feeding is known to induce focal femoral atherosclerosis in rabbits. We previously demonstrated the effectiveness of hirudin in limiting restenosis after balloon angioplasty (BA) in this double instrumentation injury (DI) model. In the present study, we sought to determine whether BA without prior air desiccation endothelial injury (single instrumentation injury (SI)) would lead to similar femoral lesions, and whether the response to this injury might also be limited by hirudin. Accordingly, 38 femoral arteries of cholesterol-fed rabbits underwent BA with (n = 18, DI group) or without (n = 20, SI group) prior air desiccation endothelial injury. Animals were killed 24 hours or 28 days after BA. Twenty-four hours after BA, the SI group (n = 10) had a significantly smaller percentage of cross-sectional area narrowing by plaque than the DI group (n = 8) (0% versus 42% +/- 9%, p = 0.008). However, 28 days after BA, the percentages of cross-sectional area narrowing by plaque in the SI (n = 10) and DI (n = 10) groups were similar (59% +/- 6% versus 68% +/- 1%, p = NS). The percentages of intima (16% +/- 3% versus 16% +/- 3%, p = NS) and media occupied by foam cells were also similar in the two groups. To test whether hirudin administration would limit arterial narrowing after injury in the SI model, we randomly assigned cholesterol-fed rabbits that had not undergone air desiccation injury to either bolus hirudin followed by repeat dosing 24 hours after BA or bolus heparin (150 U/kg) at the time of BA. The hirudin-treated group showed significantly less angiographic and histologic restenosis 28 days after BA, despite no difference in early (0 to 72 hours) cumulative cellular proliferation between the two groups. Thus, in the cholesterol-fed rabbit, plaque formation and foam cell accumulation are similar after BA of a non-air-desiccated (SI) or focally atherosclerotic (DI) artery. Thrombin inhibition with hirudin limits arterial narrowing after SI, further emphasizing the role of thrombin in neointimal growth after injury.
Barry
W L
WL
Department of Medicine, University of Virginia, Charlottesville, USA.
Wiegman
P J
PJ
Gimple
L W
LW
Gertz
S D
SD
Powers
E R
ER
Owens
G K
GK
Sarembock
I J
IJ
D000800:Angioplasty, Balloon / Q000009:adverse effects*; D000818:Animals; D002455:Cell Division; D002791:Cholesterol, Dietary; D003327:Coronary Disease / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000293:injuries*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006629:Hirudins / Q000494:pharmacology*; D008297:Male; D008954:Models, Biological; D011817:Rabbits
D002791:Cholesterol, Dietary; D005343:Fibrinolytic Agents; D006629:Hirudins