Circulation, Vol 85, 1548-1556, Copyright © 1992 by American Heart Association
H Hanke, M Oberhoff, S Hanke, S Hassenstein, J Kamenz, KM Schmid, E Betz and KR Karsch
BACKGROUND. The proliferative response induced by balloon angioplasty is
known to be an important factor in the development of restenosis after
successful coronary angioplasty. METHODS AND RESULTS. To study the effects
of low-molecular-weight heparin (LMWH) on cellular proliferation after
experimental balloon angioplasty, LMWH (3.9 kd, 400 anti-Xa units/kg/day)
was given to 20 male New Zealand White rabbits. After an intimal
fibromuscular plaque was induced by electrical stimulation in the right
carotid artery, LMWH was applied during the 7 days after balloon
dilatation. As the control group, 20 other rabbits underwent balloon
angioplasty without application of LMWH. The vessels were excised 3, 7, 14,
and 28 days after balloon treatment. During the final 18 hours before the
rabbits were killed, bromodeoxyuridine was applied. Intimal wall thickness
increased from 13 +/- 5 cell layers (preangioplasty control group) to 20
+/- 6 cell layers in the LMWH- treated group at 28 days (p less than 0.05).
In contrast, histological examination of control animals 28 days after
angioplasty revealed a significant increase to 35 +/- 15 cell layers (p
less than 0.01). Immunohistological quantification showed a significant
increase (p less than 0.001) of cells undergoing DNA synthesis at 3 (10.2
+/- 4.2%) and 7 (7.7 +/- 4.8%) days after balloon dilatation in control
animals. In contrast, at 3 and 7 days after balloon treatment, the
percentage of cells undergoing DNA synthesis in LMWH-treated rabbits was
lower (3 days, 2.7 +/- 1.8%; 7 days, 1.9 +/- 0.3%) than the corresponding
untreated controls but showed a significant increase (p less than 0.01)
compared with the preangioplasty controls. The differences between the two
groups were statistically significant, however (3 days, p less than 0.01; 7
days, p less than 0.05). As early as 14 days after angioplasty, the extent
of cellular proliferation was normalized and was comparable to the
preintervention levels in both groups. CONCLUSIONS. Our data indicate that
the proliferative response after balloon angioplasty can be reduced in vivo
by early treatment with LMWH and thus encourage further clinical
investigations.
ARTICLES
Inhibition of cellular proliferation after experimental balloon angioplasty by low-molecular-weight heparin
Department of Medicine, University of Tubingen, FRG.
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