In vitro uptake of dicarboxylic porphyrins by human atheroma. Kinetic and analytical studies.

Human atheromatous aorta segments as well as presumably disease-free control aorta were obtained at autopsy. They were incubated with solutions of various purified dicarboxylic porphyrins including hematoporphyrin (HP) and hydroxyethylvinyldeuteroporphyrin (HVD), and with solutions of Photofrin. Selective labelling of the atheroma was shown by macroscopic and microscopic observations of the characteristic porphyrin fluorescence associated with the atheromatous plaques. The time dependence of the uptake, monitored by absorption spectrophotometry or by high performance liquid chromatography, was inferred from the disappearance of the porphyrins in the incubation medium. Significant binding was observed in the absence of albumin or serum proteins. The uptake of HP was less than that of the more hydrophobic compounds HVD or Photofrin when these porphyrins were used alone. The presence of albumin or serum drastically reduces atheroma labelling. Some competition between HP and HVD for binding sites is also seen. The present results do indicate that hydrophobic porphyrins have an intrinsic affinity for atheroma and that they can be taken up through passive processes. Taking into account previous data on animal models (Photochem. Photobiol. (1989), 731-737), it appears however that, in vivo, interactions with proteins and pharmacokinetics will primarily determine plaque labelling.

Intraoperative coronary artery endarterectomy with excimer laser.

Compared with continuous-wave lasers, excimer lasers exhibit several in vitro advantages: nonthermal ablation process and linear relation between the number of pulses and the depth of the crater. A 308 nm, 20 nsec pulse duration, 1 to 5 repetition rate laser was specifically designed for clinical application. At the time of cardiopulmonary bypass in 10 symptomatic patients, before bypass grafting, a 1 mm diameter core specifically ultraviolet-tipped fiberoptic scope was introduced via the coronary arteriotomy and placed upstream (seven patients) and downstream (three patients) in contact with the stenosis. Laser power was increasingly delivered up to the clearing of the stenosis or occlusion. Quality of angioplasty was controlled by calibration of the neolumen, cardioplegic solution output through the laser-treated segment, and an eighth day or sixth month coronary arteriogram. In the first three patients studied on the eighth day, all laser-treated coronary artery segments showed an early parallel-linked patent neolumen despite competitive bypass graft flow. In the patients studied after 6 months, all recanalized segments were patent except one; in one patient the venous graft was occluded, but the upstream laser angioplasty was patent. The main limitation of the method lies in the fact that laser coronary recanalization is confined to the fiber core diameter. We conclude that (1) excimer laser angioplasty may be safe and efficient during surgical procedure and (2) as catheter flexibility remains the most critical problem, we are now assuming an appropriate tool with a multifiber system that is suitable for intraoperative as well as percutaneous routes.

XeCl excimer laser coronary angioplasty: a convergence of favourable factors.

The results of recent studies on the application of an XeCl laser to coronary angioplasty are presented. Several points are examined: the quality of the cut in human post-mortem artery, the cutting rates and threshold fluences in different media, the risks of carcinogenesis and thrombosis, and the transmission of suitable fluences in optical fibres. Recent human in vivo procedures are reported.

[Coronary endarterectomy using an excimer laser. Preliminary peroperative results]. / Endartériectomie coronaire par laser à excimères. Résultats peropératoires préliminaires.

From experimental and clinical experience, safe coronary angioplasty cannot be performed with CW lasers. The excimer laser does present a number of advantages in vitro: non-thermal ablation of plaques and a linear relationship between the number of pulses and the depth of the crater, so that tissue ablation is quantitatively predictable. A 308 nm, 20 ns pulse duration, 1 to 5 repetition rate laser was specifically designed for clinical application. During cardiopulmonary bypass prior to bypass grafting in 10 symptomatic patients, a 1 mm diameter core UV-tipped fiberoptic was introduced via the coronary arteriotomy and directed in contact with the coronary stenosis. Laser power was progressively increased until the stenosis or occlusion was recanalized. The quality of this angioplasty was controlled by calibration of he neo-lumen, cardioplegia solution flow through the lased segment, and 8th day coronary angiography. The laser treated coronary segments of the first 4 patients showed clearly parallel-lined patent neo-lumen despite competitive bypass graft flow. The main limitation of the method is that laser coronary recanalization is confined to the fiber core diameter. The authors conclude that: 1) excimer laser angioplasty is a safe and efficient intra-operative procedure; 2) the most critical problem for percutaneous laser angioplasty remains flexibility of the apparatus as the fiber diameter must be large enough to provide an adequate arterial neo-lumen.

Photofrin II uptake by atheroma in atherosclerotic rabbits. Fluorescence and high performance liquid chromatographic analysis on post-mortem aorta.

Atherosclerotic lesions were induced in normal and Watanabe rabbits by atherogenic diet and stripping of aorta endothelium. The rabbits were injected with Photofrin II and sacrificed two days later. Atheromatous aorta as well as normal aorta from control animals were characterized by their fluorescence spectra using front face excitation. Characteristic emission peaks at 631 and 694 nm were displayed at atheromatous plaques. The excitation spectrum shows a strong band at 394 nm and weaker bands at 446, 504, 536 and 574 nm. Although no fluorescence of normal aorta can be seen by visual inspection, emission with a maximum at 626 nm was detected by spectrofluorimetry. Normal phase high performance liquid chromatography analysis of extracts from atheroma and control aorta were also carried out. The specific labelling of atheroma involves mainly protoporphyrin, hematoporphyrin and also minor components of Photofrin II which are accumulated. Some other components are accumulated but do not appear to be specifically retained by atheroma.