The aim of our study was to demonstrate, in vivo, bubble expansion in blood and to assess any damage to the arterial wall after 1 - 10 excimer laser pulses (55 mJ/mm²). Time resolved flash photography demonstrated the expansion and implosion of a vapor bubble, which induced a 50% diameter increase of the artery within 75 microsecond(s) and a subsequent invagination (150 - 500 microsecond(s) ). This microsecond dilation and invagination caused extensive wall damage (up to 1.9 mm) far beyond the penetration depth of 308 nm laser light (< 100 micrometers ). The damage, which increased with the number of laser pulses, may be related to the dissections observed after excimer laser coronary angioplasty.

Tissue optics affect the observation of tissue fluorescence. This paper outlines how tissue optical properties affect the observation of fluorescence from human aorta.

Laser-induced fluorescence spectroscopy of arterial surfaces provides information about the composition of atherosclerotic plaques. The aim of the study was to determine whether accumulation of peroxidized lipoproteins in arterial walls, a process postulated to play a role in initiating atherosclerotic changes, can be demonstrated by fluorescence spectroscopy. XeCl excimer laser ((lambda) equals 308 nm) induced fluorescence of human aortas containing early lipid-rich, non-collagenous lesions exhibited marked red shifts and broadening of the fluorescence spectra compared with spectra from non-atherosclerotic aortas. Similar profiles were observed in spectra obtained from oxidatively modified LDL, but not native LDL. In hypercholesterolemic rabbits with early foam cell lesions, spectral shifts resembled those of oxidized (beta) -VLDL, the major lipoprotein accumulating in arteries of rabbits fed cholesterol. XeCl laser-fluorescence spectroscopy of arterial surfaces may be useful for the identification of arterial plaques indicative of atherosclerosis in its early and probably reversible stages.

This paper describes a combined ultrasonic and spectroscopic system for imaging both the structure and chemical composition of atherosclerotic plaque. Using this system, ultrasound pulse echo distance estimations can be used to accurately compensate detected tissue fluorescence intensities for a wide range of tissue-detector separations, D. Compensation is achieved using an empirical model, wherein fluorescence intensity decreases as 1/Dⁿ with n equals 1.1 for tissue detector separations from 2.5 to 5 mm and 1.4 for separations of 5 to 15 mm. This behavior indicates that fluorescence exiting the tissue surface is not isotropic.

The differential diagnostic capacity of a multi-directional sensing catheter with intraluminal objects was evaluated by fluorescence analysis following administration of a photosensitizer. The measurement catheter is 1.7 mm in diameter and is constructed with a cross-sectional arrangement of 6 sensor bundle units and a centered guide wire lumen. Fluorescence was analyzed by polychrometer and amplified CCD camera with an image intensifier. The excitation light was 405 nm wavelength obtained from an Xe-Hg lamp using a band pass filter. In vivo and in vitro fluorescence analysis of normal and atherosclerotic rabbit aorta was performed following intravenous administration of 5 mg/kg hematoporphyrin derivatives (HpD) 24 hours before. The multi-directional sensing catheter detected fluorescence spectra independently in real time. In vivo measurement of this catheter showed, relative to the tip of catheter, in which direction there was blood, normal intima, slight intimal thickness, which should not be treated by laser, or areas of atherosclerosis, which can be treated by laser.

In this paper we evaluate whether argon-ion laser induced fluorescence could help to discriminate atheromatous from normal tissue stained with tetracarboxylate ion dyes. Eighteen cadaveric abdominal aortic samples (9 normal, 9 atherosclerotic) from 4 autopsies were obtained in an unfixed state within 12 hours of death. They were incubated in the dye solution for two hours and then they were rinsed in saline for another two hours to ensure that only dye bound to the tissue was present during the experiment. An argon ion laser (476.5 nm) was used for excitation. Fluorescence was collected by a 600 micrometers core diameter step-index UV-visible fiber. The fiber was butt-connected to the 20 micrometers slit of a 0.25 m spectrograph. Data acquisition and analysis were performed via an optical multichannel analyzer. A characteristic increase of the fluorescence signal at the 520 to 560 nm spectral region for atheromatous tissue was observed after treatment of the samples with the dye. This allowed the development of a simple discriminatory index (spectrum integral from 520 to 560 nm vs. spectrum integral from 580 to 620 nm).

We have evaluated the angioscopic findings before and after various percutaneous techniques to treat 39 lesions in 32 cases of arteriosclerosis obliterans (ASO). We applied a laser (CL50: SLT, Japan), percutaneous transluminal angioplasty (PTA), and atherectomy -- either singly or in combination, with angioscopic luminal observation (angioscope: PF14L & PF18L Olympus, Japan) recorded before and after the treatments. In the case of a complete obstruction, we employed PTA as the first choice. We used a laser prior to PTA when the PTA guide-wire failed to penetrate the lumen. For eccentric and calcified lesions atherectomy was applied. A sufficient enlargement was obtained initially in 37 of the 39 lesions. The angioscopic observations after treatment revealed carbonization (3/5) and attachment of small thrombi (3/5) after using the laser, intimal rupture (3/8), dissection (2/8), flap formation (2/8), and attachment of small thrombi (4/8) after PTA, and attachment of small thrombi (9/19), flap formation (6/19), and dissection (2/19) after atherectomy. We established the efficacy of angioscopic assessment demonstrating beneficial clinical results. The angioscopic findings suggest that attachment of small thrombi may be responsible for a poor prognosis. Additional angioscopic observations with angiography are recommended for improved understanding of the luminal changes.

Conventional balloon coronary angioplasty has limitations for application on particular lesions, such as lesions near the left main trunk (LMT), ostial location, and highly eccentric lesions. Hence, efficacy of newly developed Holmium YAG laser coronary angioplasty (HLCA) was assessed for 24 patients with angina. Adjunctive balloon angioplasty was performed for 21 of 24 lesions. Delivered energy ranged from 1.5 to 2.5 watts/pulse and the total exposure time ranged from 6 to 32 seconds. Laser success, defined as 20% reduction of stenotic ratio, was obtained in 16 of 24 (67%) and overall procedural success rate was 92%. Follow up coronary angiography after 3 months showed restenosis in 9 of 19 patients (47%). HLCA is an acutely effective treatment for lesions identified as not ideal for balloon angioplasty. However, angiographical restenosis rate is similar to the conventional balloon angioplasty and a highly calcified complex lesion may not be a candidate for the treatment of HLCA, because of a potential risk of coronary perforation.

We report our clinical experience with a group of 14 patients who presented with acute myocardial infarction. A holmium:YAG laser was applied to the infarct-related artery. This laser emits 250 - 600 mJ per pulse, with a pulse length of 250 microseconds and repetition rate of 5 Hz. Potential benefits of acute thrombolysis by lasers include the absence of systemic lytic state; a shortened thrombus clearing time relative to using thrombolytics; safe removal of the intracoronary thrombus and facilitation of adjunct balloon angioplasty. Potential clinical difficulties include targeting the obstructive clot and plaque, creation of debris and distal emboli and laser-tissue damage. It is conceivable that holmium:YAG laser can be a successful thrombolytic device as its wave length (2.1 microns) coincides with strong water absorption peaks. Since it is common to find an atherosclerotic plaque located under or distal to the thrombotic occlusion, this laser can also be applied for plaque ablation, and the patient presenting with acute myocardial infarction can clearly benefit from the combined function of this laser system.

Mid-infrared laser wavelengths offer advantages as a source for coronary angioplasty based upon the excellent fiberoptic transmission and the enhanced tissue absorption of these photons. We report the results of a pilot clinical trial of a Holmium:YAG (2.1 micrometers ) coronary laser angioplasty using a prototype (1.6 mm and 2.0 mm) multifiber catheters. Coronary laser angioplasty with or without adjunctive balloon angioplasty or directional atherectomy was performed in 14 patients with 17 coronary stenoses. Laser success was obtained in 13/14 (93%) patients and 16/17 (94%) lesions. Uncomplicated procedural success was achieved in 9/14 (64%) patients and 12/17 (71%) lesions. Our initial laser success rate was very encouraging using this prototype multifiber catheter with a holmium:YAG laser. However, our overall procedural success rate was disappointing, and not superior to that expected with conventional angioplasty alone. The holmium laser remains an attractive energy source for laser angioplasty, but its utility is limited by catheters which create inadequate channels for stand-alone laser angioplasty.

Recently, new intravascular ultrasound devices for intracoronary use became available. The aim of the study was to evaluate the accuracy of intravascular ultrasound for the assessment of coronary artery vasomotion and endothelial function in patients with atherosclerosis. Twenty patients with luminal irregularities on coronary angiogram and a high cholesterol level (287 +/- 19 mg/dl) (group 1) and 6 patients with angiographically smooth arteries and a minimally elevated cholesterol level (197 +/- 12 mg/dl) (group 2) were studied. A mechanical intravascular ultrasound probe (4.3 French, 30 MHz, Cardiovascular Imaging Systems) was placed into the proximal segment of the coronary artery. Off-line measurements of the lumen area and calculation of mean intimal thickness indice was performed using digitized ultrasound images. Endothelial function was studied during a sympathetic stimulation by a cold pressor test and after intracoronary administration of papaverine and linsidomine. Mean intimal thickness was higher in group 1 than in group 2 (1.52 +/- 0.64 mm vs. 0.18 +/- 0.08 mm, p < 0.001). Linsidomine infusion induced a significant vasodilating effect in both groups (p < 0.001).

Despite recent technological advances in laser catheter technology and the use of guidewire guidance, clinical studies still reveal an important number of arterial wall dissections and less commonly perforations following coronary laser angioplasty. The aim of the study was to establish a simple model of atherosclerotic arterial wall and to assess the mechanical effects induced by holmium-yttrium-aluminum-garnet (Ho-YAG) laser and XeCl excimer laser (Ex). Empirical relationship between laser energy and maximal expansion distance of the targets may be established with Ho-YAG laser. Our data suggest that the excimer laser ablates tissue with less traumatic effect than Ho-YAG laser.

We used an excimer laser system (xenon-chloride at the wavelength of 308 nm) to treat totally occluded peripheral vessels in 71 patients. Energy was delivered through a multifiber catheter, which combines 12 (7F) or 18 (9F) fibers (260 (mu) diameter each), concentrically arranged. Balloon dilatation was associated to complete the procedure in 84% of the cases. The immediate success rate was 97%. The cumulative patency rate was 49% at one year. The major problems with this system were that the stiff multifiber tips caused dissections, and spasm; dead space/active space ratio of the catheter was unfavorable, allowing mechanical `dottering;' the maximum lumen obtained was considered inadequate. After this three year period, the goal of our clinical laser program is to develop a stand alone laser technique by employing a multifiber catheter which combines 130 - 150 fibers 100 (mu) diameter each, and features a quartz coated distal tip.

Excimer laser coronary angioplasty has been shown to result in high acute success rate. However, long term follow up has shown significant restenosis. To evaluate the restenosis predictive factors, we analyzed data from patients treated by excimer laser angioplasty in four French clinical centers. A cohort of 166 patients, 140 men and 26 women with mean age of 58 +/- 11 years, was enrolled in the study. Total occlusions, tubular, ostial and calcified lesions, unsuccessful balloon dilatation and/or restenosis were considered as indications for laser angioplasty. Follow-up angiography six months after the procedure was achieved in 80 patients. In conclusion, excimer laser angioplasty is associated with a high initial success rate and an acceptable major complications rate. However the use of this method is limited by significant restenosis rate.

The purpose of this study was to evaluate whether photodynamic therapy (PDT) can destroy the proliferating smooth muscle cells and therefore suppress the occurrence of restenosis after angioplasty. PDT following administration of hematoporphyrin derivatives (HpD) 24 hours before irradiation was performed on 30 rabbits immediately (0D), 3 days (3D), 1 week (1W) and 2 weeks (2W) after balloon injury. HpD accumulation of each group was investigated simultaneously. Irradiation of 27 J/10 mm² from an Hg-Xe flash lamp light transmitted through an 800 micrometers quartz fiber with a diffusing tip was used. All rabbits were sacrificed 4 weeks after balloon injury. The results were expressed in terms of intima:media thickness ratio at the site of fiber contact (I/M) and intima:media area ratio of the cross section (IA/MA). Inhibition of intimal thickening evaluated on the basis of the I/M ratio was recognized in the 3D-, 1W-, and 2W-PDT group. The most effective photoradiation was at the 1W-PDT (I/M equals 0.78 +/- 0.67), but in 2W-PDT intimal necrosis resulting in a small amount of thickness was observed with less media necrosis. ThreeD and 0D PDT effects reduced with media necrosis. We conclude that PDT after angioplasty would be an ideal preventional therapy of restenosis.

Despite four years of intensive clinical investigation, excimer laser coronary angioplasty has not been accepted by the interventional cardiology community as the intervention of choice for any lesion type. Although the preliminary analysis presented here shows that the new technology shows promise for the treatment of saphenous vein graft lesions, aorto-ostial lesions and other lesions, these lesion types account for only about 5 - 10% of cases currently targeted for angioplasty and can frequently be treated with other interventional methods. Broader use of excimer laser angioplasty requires convincing proof that the new technology has clear superiority over other interventional techniques for a wider range of lesion types. Furthermore, the mechanisms of vessel dissection, perforation and abrupt closure need further clarification. Thus, the major challenges for excimer laser angioplasty include: (1) randomized trials to document the superiority of excimer laser over balloon angioplasty; (2) improved catheter designs, including devices for eccentric lesions and total occlusions; and (3) a better understanding of laser-tissue interactions to reduce the unpredictability of unfavorable angiographic outcome.

Vasoreactivity of laser-treated coronary artery was investigated in canine left circumflex coronary artery (LCx). Excimer laser (XeCl 308 nm, 50 mJ/mm²), holmium YAG laser (2.1 micrometers , 150 mJ/pulse), or argon laser (488 nm, 3 W), were used through a single optical fiber. Two 3-mm long segments were obtained from the treated segments and controls in Krebs-bicarbonate buffer. Contraction of LCx was induced with KCl at 30 mM or 3,4 DAP and expressed as developed tension (gram; g). Eighteen dogs were used. Reduction of vasocontactility was observed in excimer treated vessels (0.17 +/- 0.24 g with KCl and 0.34 +/- 0.55 g with 3,4 DAP vs 2.13 +/- 0.85 with KCl and 3.1 +/- 1.9 with 3,4 DAP in control, P < 0.001 respectively), holmium YAG treated vessels (0.43 +/- 0.48 g with KCl and 0.46 +/- 0.24 with 3,4 DAP vs 2.42 +/- 0.49 g with KCl and 3.2 +/- 0.46 with 3,4 DAP in control, P < 0.001 respectively) and argon treated vessels (0.48 +/- 0.79 g vs 4.4 +/- 0.88 in control, P < 0.001). Either pulsed or argon laser irradiation results in loss of vasoreactivity to either constrictive or relaxation agent.

Short-term intimal heating may be effective to improve luminal geometry without deep medial injury which can induce restenosis. We developed a new laser-heated thermal balloon catheter which can quickly raise and lower the balloon temperature. To investigate the acute effect of short-term thermal balloon angioplasty (STBA) for stenotic lesions, we performed STBA following balloon angioplasty (BA) in 8 canine stenotic femoral arteries. Cw Nd:YAG laser delivery (10 W, 15 s) induced the maximum temperature of 83 degree(s)C on average. Angiography and angioscopy were performed at pre-BA, post-BA and post-STBA. The angiographical mean stenotic diameter was 1.8 mm at pre-BA, 2.2 mm* at post-BA, 2.9 mm** at post-STBA (*:p < 0.05 pre-BA vs post-BA, **:p < 0.05 pre- and post-BA vs post-STBA). The angioscopic observation revealed intimal flaps and tears in 7 lesions after BA. The luminal geometry after STBA was symmetrically expanded. However, the intimal injury was still observed although the intimal flaps were partly sealed by STBA. These results suggested that the dilatation mechanism of STBA for stenotic lesions might be attributed to preventing elastic recoil rather than to sealing intimal fragments induced by BA.

This study was designed to assess the depth and extent of chronic lesions induced by clinically relevant doses of excimer or Ho:YAG laser irradiation in an animal model of normal arterial wall. Normal iliac arteries of 14 male New Zealand rabbits were irradiated with excimer laser and 7 contralateral sites were irradiated with Ho:YAG laser. The lasers were coupled to a 1.4 and 1.5 mm multifiber wire guided catheter for excimer and Ho:YAG laser, respectively. The catheter was introduced through the carotid artery and positioned coaxially over the guide wire into the common iliac artery. After 28 days the irradiated sites were excised for light microscopy. Arterial wall lesions were assessed at the site of irradiation and at 30 mm antegrade to the site of intervention. (1) Excimer and Ho:YAG induce chronic arterial wall damage, which may result in accelerated restenosis. (2) Ho:YAG results in deeper and more extensive lesions than excimer. (3) Both lasers induce an initial vasodilation in the irradiated vessel which disappears at follow-up.

Several quantitative histopathologic markers of thermal damage that relate to tissue temperature and heating duration have been described. When a point source of heat is used the histopathologic changes radiate from the heating site to form concentric zones of tissue injury that are separated by distinct boundaries. To be detected and measured some of these markers require survival after the heating event (in vivo heating) and an intact blood flow within the targeted organ. Other markers can be found in tissues heated in vitro as well as in vivo.

Anecdotal evidence suggests that laser revascularization has long-term benefits on tissue perfusion, perhaps by stimulating angiogenesis. To test this hypothesis, we made 6 transmural channels in rat hearts randomized to either; (1) laser: channels made using a 500 micrometers diameter optic fiber coupled to a holmium:YAG laser, (2) needle: channels made using a 500 micrometers diameter needle, or (3) control: no channels made. Two months later, the rats underwent 90 minutes of coronary artery occlusion followed by 41/2 hours of reperfusion. Prior to the end of the experiment, the artery was reoccluded and the heart perfused with blue dye to detect collateral perfusion within the risk region. Microscopic analysis revealed more dye-containing vessels in needle-treated hearts than in laser or control groups (12 +/- 6*, 3 +/- 1, 2 +/- 1 vessels per field of view, * p < 0.05). Needle channels also appeared to limit necrosis: infarct size was 41 +/- 6* (needle), 61 +/- 6 (laser), 70 +/- 5 (control) % of the risk region in the three groups (*p < 0.05 versus control). Thus, needle- treatment may be capable of reducing infarct size by supplying blood via a collateral circulation apparently stimulated by the channels making process.

The design, processing, and sequential testing of a novel cylindrical diffusing optical fiber tip for ultraviolet light delivery is described. This device has been shown to uniformly (+/- 15%) illuminate angioplasty balloons, 20 mm in length, that are used in an experimental photochemotherapeutic treatment of swine intimal hyperplasia. Our experiments show that uniform diffusing tips of < 400 micron diameter can be reliably constructed for this and other interstitial applications. Modeling results indicate that this design is scalable to smaller diameters. The diffusing tips are made by stripping the protective buffer and etching away the cladding over a length of 20 mm from the fiber tip and replacing it with a thin layer of optical epoxy mixed with Al₂O₃ powder. To improve the uniformity and ease of fabrication, we have evaluated a new device configuration where the tip is etched into a modified conical shape, and the distal end face is polished and then coated with an optically opaque epoxy. This is shown to uniformly scatter approximately 70% of the light launched into the fiber without forward transmission.

Management of myocardial ischemia by direct myocardial revascularization with lasers has been attempted in the past. Although this procedure has met with considerable controversy, its original hypothesis was based on the assumption that miniscule laser channels could provide a means by which left ventricular blood could nourish ischemic myocardium. However, although numerous experimental studies have demonstrated a decrease in size, its application in a clinical setting has experienced limited success. In this present study, the issue of regional myocardial contractility was assessed in an acute ischemic canine model. In addition, the H- Yag laser was evaluated for its potential in revascularizing the myocardium and its capability of maintaining regional contractility.

Spherically shaped laser probes, primarily used in laser angioplasty to unobstruct occluded arteries have weak focusing abilities in physiological media due to index mismatching. Three- D ray tracing was developed to calculate the light distributions of aspherically modified tips (parabolic, hyperbolic, etc.). It was found that the focusing effects of aspherical silica (n equals 1.457) tips are up to 3.0 times better than those of spherical tips. It is possible to increase the irradiance of tissue in water by about 6 to 9 times using normal silica fiber without total internal reflection. Experiments were performed in air and in water using normal silica fiber without total internal reflection. Experiments were performed in air and in water using registration of light distribution with a CCD-camera and confirmed the theoretical predictions. For aspherical sapphire (n equals 1.75) tips increasing of maximum irradiance is more than 16 times than for spherical probes. The spherically modified tips are more atraumatic due to rapid decrease in fluence rate distal from the position of highest irradiance. Three-D ray tracing is useful to optimize the design of different modified tips.

In excimer laser coronary angioplasty (ELCA) an XeCl excimer laser at 308 nm is used to ablate atherosclerotic plaque in a stenosed coronary artery. In previous experiments we have seen that during ablation of cardiovascular tissues under saline, there is always a release of a stream of insoluble gas bubbles. We believe that this gas plays a crucial role in the understanding of the recanalization process in ELCA where a laser beam delivery catheter is brought in contact with the plaque in a tight space. It is well conceivable that the gas may help to recanalize an artery as a kind of dottering effect but especially in a tight stenosis the gas accumulation may enhance the damage to the vessel wall. The aim of the study was to investigate the dependency of the gas production by a XeCl excimer laser on the energy density and the diameter of the beam delivery system, to establish whether the effects of gas could be minimized or would be independent on the beam delivery system.

Exogenous chromophores have the capability to enhance atheromatous plaque ablation during laser angioplasty. A number of dyes have been tested for their effect on the tissue absorption for lasers emitting at different wavelengths, but little is known about conditions governing this selectivity. 1064 nm and 1300 nm light transmission and scattering of 0.6 mm thick samples of agar with different concentrations of talc and black ink were compared to those of atheromatous tissue of the same thickness in order to determine the sample with most similar optical properties. We measured ablation threshold in air for both wavelengths, temperatures in adjacent agar in air for both wavelengths, ablation thresholds in water for 1064 nm, temperatures in the adjacent agar in the water for 1064 nm, ablation threshold in the air for 1064 nm and 5, 10, and 15 mm fiber tip distances. Selectivity of the laser ablation is achievable by saturation of the tissue with chromophore dyes. Higher absorption results in lower thermal damage of non-ablated tissue, especially in water. Selectivity in water is more pronounced than that in air. Selectivity was not influenced by the size of the laser spot in the investigated range.