Hematoporphyrin Derivative Uptake by Atheroma in Atherosclerotic Rabbits: The Spectra of Fluorescence From Hematoporphyrin Derivative Demonstrated by an Excimer Dye Laser

Abstract

A new diagnostic and therapeutic endoscopic system consisting of an excimer pulse dye laser is presented. This report demonstrates the accumulation of hematoporphyrin derivative (HpD) in atheroma as shown by the fluorescence of HpD using this equipment. Atheroma was induced in the aorta of WHHL (Watanabe heritable hyperlipidemic) rabbits, 5 mg kg−1 HpD was injected intravenously and the rabbits were sacrificed 24 h later. The aorta was dissected and the localization of HpD was examined. Characteristic peaks of the fluorescence of HpD at 630, 665 and 690 nm wavelength were detected in the atheromatous lesion. However, in the fatty plaque, the emission peak at 630 nm was lower and the 665 nm peak faded away. No fluorescence with peaks was detected in the normal area. The ratio of fluorescence intensity in atheroma, border zones and normal areas was 10.4 : 5.0 : 1.0. On normal rabbits made atherosclerotic by diet and balloon damage, an ultra thin endoscopic catheter was inserted from the descending aorta of atherosclerotic rabbits under anesthesia. Essentially the same data was obtained by these studies in vivo as was obtained in the in vitro studies. The above data suggests the possibility of future applications of this equipment for diagnosis of atheroma.

Photofrin Ii Uptake by Atheroma in Atherosclerotic Rabbits. Fluorescence and High Performance Liquid Chromatographic Analysis on Post‐mortem Aorta

“…Such an emission band is also presented by porphyrin solutions in some detergents at premicellar concentrations and may reflect a particular organization of porphyrin molecules at lipid water interface (Miyoshi et al, 1984). We therefore do not agree with the suggestion that an extra emission band in the range 650-670 nm could be characteristic of atheroma as suggested by Okunaka et al, (1987) and Kessel (Kessel and Berguer, 1988). Studies on the accumulation of porphyrins by human atheromatous plaques from aorta obtained at autopsy have been reported by Kessel and Sykes (1984).…”

“…In vivo and in vitro emission fluorescence measurements on atheromatous aorta in atherosclerotic rabbits also showed signals similar to those recorded on tumors (Okunaka et al, 1987). These findings suggested that porphyrin binding in tumors and atheroma may be governed by similar interactions with tissue components and/or by the pharmacodynamical properties of these molecules (Okunaka et al, 1987;Pernes et al, 1988). In contrast, Kessel and Sikes (1984) found that human atheromas preferentially bind hematoporphyrin in vitro.…”

“…The nature of the component(s) effectively incorporated in the plaques and possible relations between the mechanisms leading to tumor and plaque labeling are still under debate. In an experimental animal model we found that Photofrin II@, a commercial HpD fraction enriched in dimeric and aggregated porphyrins, yielded the most important labelling (Pernes et al, 1988). Purified hematoporphyrin gave little labelling.…”

“…Recently, atheromatous plaques have been shown to be selectively labelled by hematoporphyrin derivative, suggesting that atherosclerotic lesions could be amenable to the above mentioned techniques through percutaneous catheterism (Spears et .al., 1983; Litvack et al, 1985; Pernes et al, 1988). 'To whom correspondence should be addressed.…”

Differential effect of Photofrin II on growth of human smooth muscle cells from nonatherosclerotic arteries and atheromatous plaques in vitro.

“…19 Spokojny et al 22 have shown that HpD was selectively concentrated in different types of arterial lesions in the rabbit model, whereas the media of these tissues exhibited no fluorescence, indicating a decreased or complete lack of HpD uptake. Also Okunaka et al 20 have described in detail how HpD was concentrated in atheromatous lesions of the rabbit with characteristic peaks of the fluorescence at 630, 665, and 690 nm wavelengths after exposure to an excimer pulse dye laser, which was Although DHE is regularly used in combination with photoactivation by laser energy, the results of this study indicate that the application of DHE without photoactivation is also possible for a selective inhibition of plaque cell proliferation at concentrations that do not affect smooth muscle cells from nonatherosderotic arteries. As we demonstrated recently, the photoactivation of DHElabeled smooth muscle cells in culture multiplied the differential effect of this drug (unpublished observations) and thus implicates a possible photodynamic therapy of vascular stenoses.…”