Although lasers can effectively ablate atherosclerotic plaque, their clinical application is limited by difficulties in confining the effects of laser radiation to the plaque. Inadvertent irradiation of adjacent or underlying normal artery frequently causes perforations, dissections, spasm, pain and thrombosis. The goal of this proposal is to enhance the specificity of laser radiation for plaque by the use of naturally occurring chromophores: carotenoids. These compounds accumulate in plaque but not in normal artery and enhance selectivity by increasing the absorption of laser light by plaque in a spectral region where there is minimal absorption by normal artery. The optimal carotenoids for enhancing selectivity will be determined by first identifying the carotenoids that naturally accumulate in human plaque, and then determining which of these confers the greatest preferential absorption in the shortest period of time in an animal model of atherosclerosis. Characterizing the carotenoids found in human plaque will identify molecular structural features and physical-chemical properties which confer affinity for plaque. This may also help to explain the recently discovered association of beta carotene, a common carotenoid, with a significant reduction in myocardial infarction, stroke and vascular surgery. Once the optimal carotenoids are identified, their potential for enhancing the quality and selectivity of laser atherectomy will be assessed in an atherosclerotic animal model. Identifying those human plaques which accumulate the greatest amount of carotenoids will determine which types of atherosclerotic plaque have the greatest preferential absorption and thus, are best suited for removal by selective laser atherectomy. This research not only explores fundamental aspects of the interaction of carotenoids with atherosclerotic plaque but is successful, may result in a safer, more effective method for removing atherosclerotic arterial obstructions.