Compromise of the coronary artery lumen by atheromatous plaque is primarily responsible for the morbidity and mortality associated with ischemic heart disease. Based on our discovery that hematoporphyrin derivative (HPD, a photosensitive material used clinically for the destruction of malignant neoplasms) is selectively concentrated in atheromatous plaques, the hypothesis will be tested that HPD-mediated photochemical destruction of plaques can be achieved with a catheterization technique. Experimental models of atherosclerosis to be studied include hypercholesterolemic rabbits with and without aortic balloon injury, rabbits with chronic intraaortic catheters, and WHHL rabbits with endogenous hypercholesterolemia. Technology used in HPD photoradiation therapy of tumors will be applied to the treatment of atheromatous plaques; e.g., the output of an argon-ion pumped dye laser at 631 nm will be coupled to an intra-arterial flexible quartz fiber. Two problems, among others, which require solution in attempting to apply this technology will be addressed both in vitro and in vivo: 1) the strong intraluminal absorption of 631 nm light by hemoglobin and 2) the hypoxic environment within the arterial wall, since molecular oxygen is required for a photochemical reaction to occur. Exposure of HPD-laden plaques to light will be performed either through blood, through a clear, O2-permeable balloon which displaces blood, or through blood diluted with the blood substitute Fluosol-DA. Either technique should improve both light transmission and oxygen transport to the arterial wall. Treatment parameters will be optimized to produce a favorable toxic/therapeutic differential response between plaque and normal tissues. Quantitative histologic measurements will then be performed on treated and control arterial segments to evaluate the effect of treatment on plaque size. In addition, computerized image analysis of serial angiograms will be performed to quantitate the effect of treatment on lumen size over time. If successful, this photochemical technique may permit selective plaque destruction without damage to the normal arterial wall, simultaneous treatment of multiple lesions along the length of a coronary artery, and treatment of latent, angiographically inapparent plaques. The morbidity, mortality, and health care costs associated with atherosclerotic vascular disease would thereby be markedly reduced.
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| Spears, J R (1986) Percutaneous laser treatment of atherosclerosis: an overview of emerging techniques. Cardiovasc Intervent Radiol 9:303-12 |
| Spokojny, A M; Sinclair, I N; Schnitt, S et al. (1985) Uptake of hematoporphyrin derivative by valvular vegetations in experimental infective endocarditis. Circulation 72:1087-91 |
