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Fluorescence of hematoporphyrin derivative (HPD) has been used clinically to localize malignant neoplasms because of its selective accumulation in these tissues. We tested the hypothesis that HPD may also be selectively concentrated within atheromatous plaques. 48 h after HPD injection in a variety of species, selective fluorescence of atheromatous plaques of the aorta was seen in each animal (rabbits and Patas monkey) exhibiting such lesions. No fluorescence could be demonstrated in aortic segments free of atheromatous involvement. Since the efficacy of photodynamic destruction of malignant tumors with HPD has been demonstrated in clinical studies, the observations of the present study may have therapeutic implications in atheromatosis.

Thermal fusion of intimal plaque with the arterial wall during coronary balloon angioplasty may significantly reduce the incidence of abrupt closure and may reduce the occurrence of delayed restenosis by improvement of luminal size and shape. Although Nd:YAG laser energy has been shown to be effective in the thermal fusion of plaque-arterial wall separations in vitro, the most efficient manner of energy delivery for rapid achievement of therapeutically useful equilibrium tissue temperature during laser exposure has not been defined. A comparison of weld strength achieved was therefore made between two formats of laser delivery: constant power vs. decremental power with an initial high dose followed by the minimal serial decrements necessary to maintain tissue temperature constant for 15 seconds. One hundred sixty-six tissue discs of human postmortem aorta of 11 mm diameter were studied. Intimal plaque was separated from the media, the two layers were juxtaposed, a force of 4 pounds was applied, and a fiberoptic-delivered laser beam was directed perpendicular to the tissue over a 3-mm-diameter nominal spot size. Weld strength was measured as the shear force required to separate completely the two tissue layers. The mean weld strength (75 g) achieved by use of the decremental power format was significantly higher (P less than .01) than the mean strength (32 g and 56 g) achieved by using constant power for 20 and 30 seconds, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

In recent years, rapid progress in the application of lasers to the percutaneous treatment of atherosclerosis has been made. An overview of this progress is provided herein in terms of a description of promising laser approaches and problems to be solved. Direct vaporization of obstructing atheroma with fiberoptic delivery of laser energy has been associated with a high incidence of mural perforation, but each of a variety of techniques, including those for improved energy delivery, plaque recognition, alignment of the fiberoptic, and, perhaps, reduction of unnecessary thermal injury, has shown promise for reducing this complication. Nonablation applications of laser energy may also have a role in the treatment of atherosclerosis. During laser balloon angioplasty, the tissue coagulation effects of laser-thermal energy may be used during balloon inflation to eliminate arterial dissections and to reduce elastic recoil, thereby potentially eliminating abrupt reclosure and, perhaps, reducing the incidence of restenosis associated with conventional balloon angioplasty. Photochemical destruction of viable plaque tissue and vasa vasorum with porphyrins and intraarterial light represents a nonthermal, laser-based approach that could have a prophylactic role in slowing progression of diffuse atherosclerotic disease. The remarkable versatility of lasers is responsible for the multiplicity of approaches being investigated and for the current optimism that lasers will eventually play an important role in the percutaneous treatment of atherosclerosis.

Hematoporphyrin derivative, a photosensitive material used to identify and treat neoplastic tissue in humans, has been found to localize in atheromatous plaques in animals and has recently been found in postmortem human atherosclerotic plaques. It is not known whether human plaques take up hematoporphyrin derivative in vivo. In five patients undergoing surgical vascular procedures, specimens containing atheromatous plaques were removed and immediately incubated in autologous oxygenated blood at 37 degrees C with hematoporphyrin derivative at a clinically relevant concentration for 2 hours. On exposure to ultraviolet light, porphyrin fluorescence was noted throughout each plaque, whereas adjacent plaque-free tissue showed no fluorescence. To compare in vitro with in vivo hematoporphyrin derivative uptake by plaques, the fluorescence of three types of arterial lesions (induced by a high cholesterol diet, catheters or balloon injury) was studied in 16 New Zealand White rabbits. Each lesion fluoresced selectively with the same intensity whether hematoporphyrin derivative exposure was performed in vitro or in vivo. Fluorescence microscopy did not show a difference in the pattern of hematoporphyrin derivative fluorescence between in vitro and in vivo specimens. The results suggest that human atheromatous plaques should take up hematoporphyrin derivative in vivo and are, therefore, potentially suitable for photochemical treatment as a new therapeutic approach to atherosclerosis.

Widespread arteriosclerotic lesions were detected by histological examinations of rats killed at seven or nine weeks after an intrarenal (ir) injection of nickel subsulfide (Ni3S2, 5 mg per rat). Arteriosclerotic plaques were readily visualized by administering hematoporphyrin derivative (HPD) iv to rats at 24 hours before sacrifice. At necropsy, the major arteries were inspected under ultraviolet light, revealing patches of intense HPD-fluorescence in the arterial endothelium of Ni3S2-treated rats, but not in control rats. Consistent with previous reports, the Ni3S2-treated rats developed pronounced erythrocytosis; blood hematocrit values averaged 70 +/- 4 percent at seven weeks after ir injection of Ni3S2 (P less than 0.001 vs corresponding value of 49 +/- 2 percent in vehicle controls). At seven weeks, blood platelet counts averaged 17 percent lower and serum glucose concentrations averaged 23 percent lower in Ni3S2-treated rats than in controls; serum lipids, lipoproteins, non-protein nitrogen constituents, electrolytes, proteins, and enzymes were not significantly affected. Body weights and systolic blood pressures of rats at two, four, and six weeks after ir injection of Ni3S2 did not differ from corresponding values in controls. Addition of egg yolk to the diet caused mild hypercholesterolemia, but it did not enhance the incidence or severity of arterial lesions in Ni3S2-treated rats. These findings exclude hypertension and hyperlipidemia as pathogenic factors in Ni3S2-induced arteriosclerosis.

Dehiscence of portions of atheromatous plaques fractured during percutaneous transluminal coronary angioplasty may contribute to both abrupt reclosure and gradual restenosis. Laser balloon angioplasty has been shown to be effective in welding human plaque-arterial wall separations in vitro by heating tissues with a Nd:YAG laser during balloon inflation. To define the potentially useful therapeutic range of tissue temperature required to achieve thermal welds, 220 1-cm diameter discs of human postmortem atheromatous aortic tissue, the intimal plaque of which had been separated from the media, were exposed to 3-25 watts of Nd:YAG laser radiation delivered over a 12-mm2 nominal spot size for 20 seconds via a 400-micron core optical fiber. As measured with a thermistor, adventitial temperature reflected the temperature at the plaque-media junction to within 10 degrees C. The degree of tissue temperature elevation was related to delivered energy, while effective tissue penetration increased to maximum depth of 3 mm at the highest power density. Strength of tissue welds was defined as the force required to shear opposing layers of welded segments. Adventitial tissue temperatures below 80 degrees C were not associated with appreciable welds, while equilibrium temperatures between 95 degrees C and 140 degrees C were consistently associated with effective mean weld strengths, which increased linearly from 25 to 110 g, respectively. Temperatures greater than 150 degrees C were associated with rapid tissue dehydration and charring. These data suggest that the therapeutic range of tissue temperature that provides effective thermal fusion of intima-media separations is broad and that the depth and degree of thermal coagulation can be controlled by manipulation of laser energy delivery.