Goal. The long term objective of this project is to improve the safety and efficacy of percutaneous balloon angioplasty by establishing a scientific basis for determining the optimal dilation method based on measurements of the mechanical behavior atherosclerotic lesions. Background. At present, due to lack of direct evidence for the mechanism of angioplasty, balloon dilation methods vary widely, and conflicting approaches to choosing the rate, maximum distension, duration, and frequency of inflations are advocated by experienced operators. As a result, patients may not be receiving maximal benefit of the procedure.
Specific Aims. The immediate aim of this study is to determine the optimal method for balloon dilation by systematically testing the influence of inflation characteristics on dilation results in atherosclerotic arteries, then applying these findings to prospective studies. Rationale. Effective dilation of a given arterial lesion requires permanent physical alteration which, in turn, requires that it be stretched beyond its elastic limit. Safe dilation requires that any plaque disruption occur in a """"""""safety-glass"""""""" pattern, consisting of micro-fractures rather than single, large tears which lead to dissection. The strain rate required to achieve this effect and the elastic limit for atherosclerotic arteries are not known. These and other factors affecting response to dilation can be assessed in vivo in using a novel method based on measurement of the pressure-volume relation of the lesion via the catheter. Design. Four stages will be used: (1) validation of the method of pressure-volume monitoring in excised, superfused arteries and in vivo, (2) determination of the effect of atherosclerosis on arterial properties, (3) identification of the optimum inflation method(s) for in vitro arteries as a function of the type and severity of atherosclerotic lesion, and (4) application of the optimal in vitro method to identify optimal inflation protocol. Mechanical behavior will be assessed in terms of passive and active visco-elastic parameters. Optimum outcome will be defined in terms of directly-measure pressure-flow and pressure-volume relations for in vitro studies and in terms of quantitative-arteriographically determined pressure-flow relations. Lesions will be classified according to gross and microscopic pathologic characteristics. Significance. This study has immediate applications to treatment of atherosclerotic vascular disease, and findings may contribute to knowledge of the mechanism of balloon angioplasty. The effect of diffuse atherosclerosis on coronary flow dynamics, and the effect of active arterial tone on angioplasty outcome.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
1R29HL043379-01
Application #
3472821
Study Section
Cardiovascular Study Section (CVA)
Project Start
1989-07-01
Project End
1994-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Demer, Linda L; Tintut, Yin (2003) Mineral exploration: search for the mechanism of vascular calcification and beyond: the 2003 Jeffrey M. Hoeg Award lecture. Arterioscler Thromb Vasc Biol 23:1739-43
Honda, H M; Hsiai, T; Wortham, C M et al. (2001) A complex flow pattern of low shear stress and flow reversal promotes monocyte binding to endothelial cells. Atherosclerosis 158:385-90
Parhami, F; Demer, L L (1997) Arterial calcification in face of osteoporosis in ageing: can we blame oxidized lipids? Curr Opin Lipidol 8:312-4
Parhami, F; Morrow, A D; Balucan, J et al. (1997) Lipid oxidation products have opposite effects on calcifying vascular cell and bone cell differentiation. A possible explanation for the paradox of arterial calcification in osteoporotic patients. Arterioscler Thromb Vasc Biol 17:680-7
Watson, K E; Demer, L L (1996) The atherosclerosis-calcification link? Curr Opin Lipidol 7:101-4
Fyfe, A I; Stevenson, L W (1995) Enhanced monocyte transendothelial migration into graft-specific vessel wall cocultures after cardiac transplantation. Transplant Proc 27:1958-9
Bostrom, K; Watson, K E; Stanford, W P et al. (1995) Atherosclerotic calcification: relation to developmental osteogenesis. Am J Cardiol 75:88B-91B
Watson, K E; Bostrom, K; Ravindranath, R et al. (1994) TGF-beta 1 and 25-hydroxycholesterol stimulate osteoblast-like vascular cells to calcify. J Clin Invest 93:2106-13
Qiao, J H; Xie, P Z; Fishbein, M C et al. (1994) Pathology of atheromatous lesions in inbred and genetically engineered mice. Genetic determination of arterial calcification. Arterioscler Thromb 14:1480-97
Fyfe, A I; Harper, C M; Stevenson, L W et al. (1994) Human mononuclear cell adhesion to porcine arterial endothelium. Transplant Proc 26:1145-6

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