Biomedical Engineering Reference
In-Depth Information
Abnormal growth of smooth muscle lining the arterial walls plays an important
role in vascular occlusion during CAD. It also contributes to the blockage of coro-
nary arteries that have been opened by balloon angioplasty or replaced in bypass
operations. Although the initial success rate of PTCA for opening obstructed coro-
nary arteries reaches 95%, restenosis occurs at the site of angioplasty. Of the
estimated 1 million stents implanted annually in major markets, approximately
20-25% of patients treated with conventional, bare metal stents need a second
procedure within 6 months because the vessel can develop reblockage.
This is a big clinical and economic problem because the number of PTCAs is
increasing in recent years. Long-term failure negate the beneficial effects of PTCA
and after three unsuccessful PTCAs, the patient needs a coronary artery bypass
operation. Development in coronary stenting is changing the picture. Apart from
improved mechanical design, the stents are being coated with anything from hepa-
rin and antiplatelet drugs to growth factor inhibiting agents to prevent restenosis.
The two potential complications, thrombosis and intimal hyperplasia, still remain
issues that need to be addressed.
Pathomechanism
The mechanism of restenosis following angioplasty has been studied intensively.
The primary pathophysiological mechanism involves an exaggerated healing
response of the smooth muscle to vascular injury. Injury induces smooth muscle cells
to proliferate and migrate to the subintimal layer, where the smooth muscle
continues to proliferate and secrete extracellular matrix. These processes cause the
neointimal mass to expand and gradually encroach on the coronary lumen. Various
explanations of this are:
1. Atherosclerosis is sometimes considered to be a form of benign neoplasia.
2. Smooth muscle cells derived from restenotic lesions show a higher intrinsic
migratory activity than cells derived from primary lesions. A lesion that has a
higher proportion of these biologically aggressive cells will develop more steno-
sis than a lesion without similar biological characteristics.
3. Removal of inhibitory influences. Endothelial cells normally secrete nitric oxide
(NO) and heparan sulfate both of which inhibit smooth muscle cell proliferation.
Their removal by mechanical trauma of angioplasty contributes to a proliferative
environment.
4. Induction of stimulatory influences. Platelets adhere to the injured vessel and
cause a thrombus to develop at the site of injury. Free radicals and various cytok-
ines released during the vascular injury increase the expression of cell adhesion
molecules.
5. Activation of cell signal pathways induces the cell to move from a quiescent to
a proliferative state. Enzyme cyclin-dependent kinase 2 (cdk 2) may play an
important role in neointima formation.
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