DETERMINING THE OPTIMAL DOSE OF PHOTOFRIN® IN MINISWINE ATHEROSCLEROTIC PLAQUE

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Abstract
The purpose of this study was to determine the lowest dose of Photofrin (P) that would produce a 3:1 or greater ratio between atherosclerotic (AS) and control arterial walls. Aortoiliac AS was created in 24 Yucatan miniswine by a combination of balloon endothelial injury and 2% cholesterol and 15% lard diet for 7 weeks. Arteriography was then performed to demonstrate AS lesions. Following this, swine were given intravenously P in one of the following single dosages: 2.5, 1.0 or 0.5 mg/kg. Twenty-four hours later, swine were sacrificed and aortoiliac and control carotid artery segments removed and photographed with ultraviolet light to differentiate fluorescent from nonfluorescent areas. Arterial specimens were submitted for histologic analysis and chemical extraction for determination of fluorescence using a spectrofluorometer. Tissue concentration (ng/g tissue) of P from AS vessels were: Group I, 130.4 +/- 82.7; Group II, 10.0 +/- 1.2; and Group III, 9.1 +/- 0.6, respectively (P < 0.05). Ratios of P concentration in AS: control vessels were: Group I, 8.1 +/- 13.7; Group II, 1.1 +/- 0.2; and Group III, 0.9 +/- 0.1, respectively (P < 0.05). These results demonstrated that a P dose of 2.5 mg/kg provided at least a 3:1 ratio between AS: control artery wall.