The paradigm of restenosis following percutaneous transluminal coronary angioplasty.
Restenosis after successful percutaneous transluminal coronary angioplasty remains a major clinical problem limiting the long-term efficacy of this treatment for coronary artery disease. All clinical attempts to reduce the incidence of restenosis have failed. Recent advances in the understanding of the cellular biology of restenosis indicate that intimal hyperplasia is the predominant cause for restenosis. The neo-intimal proliferative response to injury is due to an interaction of platelet-fibrin thrombus and smooth muscle cells, release of mitogens, followed by a secretion of extracellular matrix. Based on these concepts concerning the biology of restenosis, several proposals have been made as regards research into potential forms of therapy. Low molecular weight heparin (LMWH) has documented antiproliferative effects on smooth muscle cells in cell cultures. Animal studies with LMWH in rabbits have demonstrated considerable inhibition of smooth muscle cell proliferation during the first 7 days after balloon angioplasty, resulting in only a moderate increase of intimal wall thickness after 28 days. In a first pilot study, application of LMWH was adjusted according to the dosage that resulted in a significant reduction of smooth muscle cell proliferation in the experimental setting. A specific delivery protocol was used, according to the previous documented time course of smooth muscle cell proliferation after vascular injury. The results of this safety trial indicate a promising therapeutic option for prevention of restenosis following coronary angioplasty.
Preisack
M B
MB
Department of Cardiology, Tübingen University, Germany.
Karsch
K R
KR
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D003327:Coronary Disease / Q000209:etiology / Q000628:therapy*; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D006801:Humans; D006965:Hyperplasia / Q000209:etiology / Q000517:prevention & control; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D011817:Rabbits; D012008:Recurrence; D017539:Tunica Intima / Q000473:pathology
D006495:Heparin, Low-Molecular-Weight