The objective of this project is to evaluate factors important in the immediate and long term healing response to laser ablation in arterial tissue. Although many laser systems can ablate atherosclerotic plaque in vivo, there is little data on the biologic response of vascular tissue-to thermal and other lightinduced injuries. Experimental goals will start with the determination of the Arrhenius thermal damage integral as a function of temperature-time exposure for both arterial cell viability (endothelial and vascular smooth muscle) in tissue culture and arterial wall structural protein denaturation. The arterial intimal surfaces, irradiated by these lasers to achieve specific damage integrals, will be studied for several purposes: to determine how hospitable the surfaces become after thermal injury to endothelial cell attachment and migration, identify what effect the thermally denatured surfaces have on platelet adherence, and the effect of thermal damage on arterial wall compliance. This data can be useful to identify the optimal postlaser conditions for laser recanalization or the application of laser technology as an adjunct with other procedures.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL002583-04
Application #
2210213
Study Section
Special Emphasis Panel (SRC (JQ))
Project Start
1991-07-01
Project End
1996-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
4
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
Heckenkamp, J; Adili, F; Kishimoto, J et al. (2000) Local photodynamic action of methylene blue favorably modulates the postinterventional vascular wound healing response. J Vasc Surg 31:1168-77
Adili, F; Statius van Eps, R G; LaMuraglia, G M (1999) Significance of dosimetry in photodynamic therapy of injured arteries: classification of biological responses. Photochem Photobiol 70:663-8
Heckenkamp, J; Leszczynski, D; Schiereck, J et al. (1999) Different effects of photodynamic therapy and gamma-irradiation on vascular smooth muscle cells and matrix : implications for inhibiting restenosis. Arterioscler Thromb Vasc Biol 19:2154-61
Statius van Eps, R G; Mark, L L; Schiereck, J et al. (1999) Photodynamic therapy inhibits the injury-induced fibrotic response of vascular smooth muscle cells. Eur J Vasc Endovasc Surg 18:417-23
Adili, F; Statius van Eps, R G; Flotte, T J et al. (1998) Photodynamic therapy with local photosensitizer delivery inhibits experimental intimal hyperplasia. Lasers Surg Med 23:263-73
Statius van Eps, R G; ChandraSekar, N R; Hasan, T et al. (1998) Importance of the treatment field for the application of vascular photodynamic therapy to inhibit intimal hyperplasia. Photochem Photobiol 67:337-42
Statius van Eps, R G; Adili, F; Watkins, M T et al. (1997) Photodynamic therapy of extracellular matrix stimulates endothelial cell growth by inactivation of matrix-associated transforming growth factor-beta. Lab Invest 76:257-66
Statius van Eps, R G; LaMuraglia, G M (1997) Photodynamic therapy inhibits transforming growth factor beta activity associated with vascular smooth muscle cell injury. J Vasc Surg 25:1044-52; discussion 1052-3
LaMuraglia, G M; Adili, F; Karp, S J et al. (1997) Photodynamic therapy inactivates extracellular matrix-basic fibroblast growth factor: insights to its effect on the vascular wall. J Vasc Surg 26:294-301
Statius van Eps, R G; Adili, F; LaMuraglia, G M (1997) Photodynamic therapy inactivates cell-associated basic fibroblast growth factor: a silent way of vascular smooth muscle cell eradication. Cardiovasc Res 35:334-40

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