In an effort to develop new, more effective forms of angioplasty, we have sought to better understand the nature of focal coronary stenoses and their acute and chronic responses to intervention. Through the development of the clinical use of intravascular ultrasound (IVUS), we have shown that the composition and stiffness at focal chronic stenoses is remarkably different from adjacent angiographically normal vessel segments, whereas the total mass of atheroma is remarkably similar. The principal lesions currently treated by angioplasty have become rigid due to fibrosis and calcification, which prevent compensatory dilatation observed in more compliant (though heavily diseased) segments. Accordingly, successful interventions disrupt/alter the stiff constraining elements to irreversibly make them sufficiently compliant to permit vessel expansion. Successful therapy requires segmental (limited) rupture of the stiff annulus and creation of a large compliant arc. Acoustic transients created by rapid bubble expansion are the principal cause of this disruption in laser angioplasty. Directional atherectomy creates deep focal excisions that can make a small arc (~60~) highly compliant. Rotablators remove luminal calcification, thereby reducing wall stiffness. Following the expansion of """"""""rigid"""""""" metallic stents at high pressures, the surrounding tissues generate significant compressive forces, causing an acute and chronic compressive narrowing of treated lesions that may be the major cause of restenosis. Transient, moderate (~60~C) thermal elevations associated with thermal angioplasty elicit a profound dose-dependent proliferative response similar to that seen with severe mechanical injury.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Intramural Research (Z01)
Project #
1Z01RR010378-03
Application #
3767462
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
1994
Total Cost
Indirect Cost
Name
National Center for Research Resources
Department
Type
DUNS #
City
State
Country
United States
Zip Code