The specific aim of this project is to characterize the structural and physical processes that participate in the metabolic balance of arterial walls by applying the principles of bionengineering and mass transport. The long-term objective is to gain new knowledge relevant to the in situ physical-chemical mechanisms and underlying structural features responsible for the intimal accumulations of atherosclerosis. The transmural transport of ferritin and of radiolabeled (Idodine 125) albumin, HDL, and LDL across the intact and de-endothelialized intimal surfaces of adult minipig arteries and veins will be studied in a specifally designed in vitro system. This system permits discrete experimental control of pertinent variable such as local chemical milieu, pressure, wall stretch, etc., at 12 contiguous sites along the length of the vessel. The uptake (M nmol cm-2) and the transmural concentration distribution (c(chi) nmol cm-3) of the labeled protein will be measured as a function of duration (T) of exposure, transmural pressure (P), wall strain (S), endothelial damage, temperature, and local chemical milieu. The c(chi) will be calculated from microdensitrometric measurements of silver distribution across microautogradiographic preparations. The c(chi) data will be correlated with structural detail from adjacent light and electron micrographs (SEM and TEM). The three main classes of blood vessels, vein (jugular), elastic artery (thoracic aorta), and muscular artery(cartoid or ilio-femoral0, will be studied in the above manner from each of the following: normal adult equal 24 mo), aged (equal 12yr), balloon-injured, and hypercholesterolemic minipigs. The c(chi) data from these vessels will fitted to tentative mathematical models to obtain numerical estimates of the parameters describing the underlying physical and chemical process. With this information, we may begin to understand 1) the mechanisms by which certain sites in the vascular tree are essentially unaffected by atherosclerosis, while others characteristically progress to the atheromatous plaque, 2) how to design rational strategies for prevention and therapy of vascular disease, and 3) how to develop enduring surgical replacement procedures.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL029095-07
Application #
3340281
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1985-09-01
Project End
1990-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
7
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
Fry, Donald L (2002) Arterial intimal-medial permeability and coevolving structural responses to defined shear-stress exposures. Am J Physiol Heart Circ Physiol 283:H2341-55
Henderson, J M; Aukerman, J A; Clingan, P A et al. (1999) Effect of alterations in femoral artery flow on abdominal vessel hemodynamics in swine. Biorheology 36:257-66
Fry, D L; Herderick, E E; Johnson, D K (1993) Local intimal-medial uptakes of 125I-albumin, 125I-LDL, and parenteral Evans blue dye protein complex along the aortas of normocholesterolemic minipigs as predictors of subsequent hypercholesterolemic atherogenesis. Arterioscler Thromb 13:1193-204
Friedman, M H; Fry, D L (1993) Arterial permeability dynamics and vascular disease. Atherosclerosis 104:189-94
Fry, D L; Haupt, M W; Pap, J M (1992) Effect of endothelial integrity, transmural pressure, and time on the intimal-medial uptake of serum 125I-albumin and 125I-LDL in an in vitro porcine arterial organ-support system. Arterioscler Thromb 12:1313-28
Fry, D L; Pap, J M (1992) Effect of various blood-derived and semisynthetic nutrient media on in vitro uptake of 125I-albumin across the intact porcine aortic endothelial surface in an organ-support system. Arterioscler Thromb 12:357-68
Pap, J M; Hammer, D F; Fry, D L et al. (1990) Nucleotide profiles in normal minipig arterial tissue. Arteriosclerosis 10:745-50
Pap, J M (1990) Long-term follow-up of catheter-induced intimal injury from routine coronary angiography in moderately hypercholesterolemic minipigs. Cathet Cardiovasc Diagn 20:139-49
Fry, D L (1987) Mass transport, atherogenesis, and risk. Arteriosclerosis 7:88-100
Pap, J M (1987) Catheter-induced intimal injury during routine coronary catheterization in dogs. Cathet Cardiovasc Diagn 13:57-73

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