Single-dose intramuscular administration of sustained-release Angiopeptin reduces neointimal hyperplasia in a porcine coronary in-stent restenosis model.
BACKGROUND
In-stent restenosis results primarily from neointimal hyperplasia. In a previous study we showed that continuous subcutaneous Angiopeptin infusion for 1 week significantly reduces neointimal hyperplasia in a porcine coronary overstretch in-stent restenosis model. The present study evaluated the relative efficacy of immediate-release and sustained-release Angiopeptin in the same model.


METHODS
Thirty pigs (n = 10 in each group) were randomly assigned to three groups: controls receiving no Angiopeptin (Group 1); a sustained-release treatment group receiving one time intramuscular administration of 20 mg of Angiopeptin (Group 2); and a systemic treatment group receiving continuous Angiopeptin over a 1-week period via a subcutaneous osmotic pump (200 micrograms/kg total dose) (Group 3). One oversized Palmaz-Schatz stent (mean stent/artery = 1.25) was subsequently implanted in the left anterior descending coronary artery. The degree of neointimal reaction was evaluated 4 weeks later by angiography (maximal per cent diameter stenosis) and histology (maximal neointimal area corrected for injury score).


RESULTS
A trend towards a reduction in diameter stenosis was observed by angiography, despite a similar degree of injury (25 +/- 17% in Group 1, 13 +/- 8% in Group 2, and 14 +/- 9% in Group 3; P = 0.072 by ANOVA). Histology demonstrated that both Angiopeptin treatment strategies significantly reduced in-stent neointimal area compared with the control group (1.65 +/- 0.97 mm2 in Group 1 versus 0.93 +/- 0.41 mm2 in Group 2 versus 0.85 +/- 0.28 mm2 in Group 3; P = 0.016 by ANOVA). Measurement of plasma Angiopeptin levels revealed comparable levels in both treatment groups, which persisted for up to 2 weeks.


CONCLUSIONS
This study shows that single-dose intramuscular administration of sustained-release Angiopeptin reduces in-stent restenosis as effectively as the prolonged systemic treatment requiring a subcutaneous pump. Thus, a practical, effective, pharmacologic therapy for preventing in-stent restenosis may be available and should be evaluated in patients.
Hong
M K
MK
Department of Internal Medicine (Cardiology Division), Washington Hospital Center, Washington, District of Columbia, USA.
Kent
K M
KM
Tio
F O
FO
Foegh
M
M
Kornowski
R
R
Bramwell
O
O
Cathapermal
S S
SS
Leon
M B
MB
D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017023:Coronary Angiography; D003327:Coronary Disease / Q000097:blood / Q000000981:diagnostic imaging / Q000601:surgery*; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology; D006965:Hyperplasia / Q000188:drug therapy; D007273:Injections, Intramuscular; D009842:Oligopeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010456:Peptides, Cyclic; D011863:Radioimmunoassay; D011897:Random Allocation; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D015607:Stents; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects* / Q000473:pathology
D002317:Cardiovascular Agents; D009842:Oligopeptides; D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin