Early and late healing responses of normal canine artery to excimer laser irradiation

Acute in vitro histologic studies have shown that the pulsed xenon chloride excimer laser causes precise microablation without the surrounding thermal tissue injury associated with frequently used continuous-wave lasers such as the argon, carbon dioxide, and neodymium:yttrium aluminum garnet lasers. However, the in vivo healing response of artery wall to excimer laser injury is not known. Accordingly, a xenon chloride excimer laser (308 nm, 40 nsec pulse width, 39 mJ/mm2/pulse) was transmitted via a 600 micron fused silica fiber to create 420 craters of varying depths (30 to 270 micron) in 21 normal canine femoral and carotid arteries. At 2 hours, 2 days, 10 days, and 42 days after excimer laser ablation, the artery segments were perfusion fixed in situ and analyzed by light, scanning, and transmission electron microscopy. At 2 hours, craters were covered by a carpet of platelets and entrapped red blood cells. Fibrin and exposed collagen fibers were seen at the crater base. There was a sharp demarcation of the crater-artery wall interface without lateral laser tissue injury. At 2 days, adherent platelets persisted with thrombus covering the base of the craters. Early healing responses were present, consisting of polymorphonucleated leukocytes and new endothelial cells, which extended over the crater rims. At 10 days, no thrombi were seen, and healing continued with almost complete reendothelialization. Macrophages, fibroblasts, fibrin, and entrapped red blood cells were present below the reendothelialized surface. At 42 days, healing was complete with obliteration of the craters by fibrointimal ingrowth. The surface was completely covered by a smooth monolayer of axially aligned endothelial cells. There were no aneurysms or surface hyperplastic responses. These favorable healing responses in normal canine arteries suggest that pulsed lasers with high tissue absorption coefficients, such as the xenon chloride excimer laser, may be suitable energy sources for clinical laser angioplasty procedures. However, further studies in atherosclerotic animals are required before human clinical responses can be accurately predicted.     

Acute effects of a copper vapour laser on atheroma

The acute histological effects of a commercially available copper vapour laser (CVL) on normal and atherosclerotic arterial wall were studied. The multi-cyclic CVL produces a quasi continuous wave output at 511 nm (green) and 578 nm (yellow) [green/yellow ratio 21]. Tissue craters were produced in segments of normal and atherosclerotic human femoral artery using a maximum of 8 J of laser energy delivered with a bare 1 mm quartz fibre in contact and perpendicular to the tissue. Crater dimensions and ablation volumes were determined histologically using an optical graticule. Ablation of atheroma was almost three times more efficient than ablation of normal arterial wall (p<0.001). A narrow zone of vacuolization and coagulative thermal damage lined the crater margins suggesting a predominantly photothermal ablative mechanism. In conclusion, selective ablation of atheroma using low power copper vapour laser light is possible. The CVL is an attractive alternative to the argon ion laser because of its low running costs and applicability to other medical disciplines. Therefore, its potential application in laser angioplasty merits further study, preferably using a modified optical fibretip delivery system.     

XeCl laser ablation of atherosclerotic aorta: optical properties and energy pathways.

The energetics of 308-nm excimer laser irradiation of human aorta were studied. The heat generation that occurred during laser irradiation of atherosclerotic aorta equaled the absorbed laser energy minus the fraction of energy for escaping fluorescence (0.8-1.6%) and photochemical decomposition (2%). The absorbed laser energy is equal to the total delivered light energy minus the energy lost as specular reflectance (2.4%, air/tissue) and diffuse reflectance (11.5-15.5%). Overall, about 79-83.5% of the delivered light energy was converted to heat. We conclude that the mechanism of XeCl laser ablation of soft tissue involves thermal overheating of the irradiated volume with subsequent explosive vaporization. The optical properties of normal wall of human aorta and fibrous plaque, both native and denatured were determined. The light scattering was significant and sufficient to cause a subsurface fluence (J/cm2) in native aorta that equaled 1.8 times the broad-beam radiant exposure, phi o (2.7 phi o for denatured aorta). An optical fiber must have a diameter of at least 800 microns to achieve a maximum light penetration (approximately 200 microns for phi o/e) in the aorta along the central axis of the beam.     

An experimental study of excimer laser angioplasty]

An excimer laser, which is a pulsed ultraviolet laser and ablates tissue precisely with no thermal injury, is expected to coronary laser angioplasty. We transmitted XeCl excimer laser (308 nm) via a 400 microns fused silica fiber. In the first experiment, we studied about excimer laser ablative effects to normal canine arteries and atherosclerotic rabbit aortas, and about healing responses following excimer laser irradiation in both models. Surfaces after excimer laser ablation were slightly rough but no thermal injury was found in the media. And for healing process of normal canine arteries, endothelial cells appeared at 3 weeks and completely covered surfaces with fibrointimal ingrowth at 3 months. In the rabbit aortas, at 3 weeks there was reconstruction of the surface. At 2 months no accelerated atherosclerotic or aneurysmal changes were observed. In the second, with this excimer laser (short pulse) and 400 microns fused silica fibers (distal fiber-end power: 3-6 mJ/pulse), we performed transluminal laser angioplasty to recanalize totally occluded canine femoral arteries under an angioscopic guidance. We cold recanalize 8 of 9 totally occluded arteries with no thermal injury of adjacent tissue, though perforations were observed in 7 of 9 arteries. In the third, we used a newly-developed long pulse excimer laser, with which distal fiber-end energy was about 3 to 4 times as much as the short pulse one, to recanalize totally occluded canine arteries. In result, recanalization was performed in 6 of 8 arteries rapidly with little thermal injury. However, we observed perforations in 6 of 8 arteries like the short pulse one. Multifiber catheter ("over the wire system") coupled with this long-pulse excimer laser was used to reconstruct stenotic iliac arteries of atherosclerotic rabbit models. The procedure was successful in all the 5 rabbits. In conclusion, our preliminary results suggested that further developments of a more powerful and longer pulse-duration excimer laser, optic delivery system and guidance system would make excimer laser angioplasty safer and more effective method in the near future.     

Arterial response to laser operation for removal of atherosclerotic plaques

The cellular response of normal and atherosclerotic aortic intima after exposure in vivo to a 0.9 mm diameter carbon dioxide laser was examined in hypercholesterolemic swine with light and electron microscopy to evaluate tissue damage, thrombosis, and healing. At energy levels of greater than 5 joules, laser burns appeared as craters less than 1 mm in depth and 2 mm in diameter. Two days after the operation, craters were filled with platelet-fibrin thrombi that did not protrude above the level of adjacent endothelium. The internal elastic lamina was exposed 1 to 2 mm around the crater. This area was surrounded by a ring of densely packed leukocytes at the edge of the normal endothelium. Two weeks after the operation, the depressed crater surface was mostly reendothelialized with small, closely packed endothelial cells. The subjacent thrombus contained numerous phagocytic cells with inclusion of fibrin, erythrocytes, and membranous debris. Proliferative invaginations containing medial smooth muscle cells, mitotic figures, and collagen extended into the pit from the lateral aspects. Eight weeks after the operation, the burned area was still depressed and therefore less occlusive than adjacent lesion areas, and a fibrous cap had formed over the remaining necrotic area. The results suggest that a focused, low-energy carbon dioxide laser can be used to remove focal atherosclerotic plaques from arteries without inducing excessive thrombogenicity. Rapid healing, including reendothelialization and intimal fibrous scarring, with minimal damage to surrounding tissue, was observed.     

Factors influencing the ablation of atherosclerotic plaque with the argon laser

This paper describes the ablative effect of argon laser light, delivered fibre optically in vitro, on 234 segments of atherosclerotic human aorta. Variables such as energy density, type of atheroma and immersion media were taken into account. All irradiated specimens were subsequently submitted to histological examination and crater volumes in mm³ were derived from micrometer measurements made at light microscopy. Results showed: (1) a linear relationship between energy dose and crater volume in fibrous atheroma; (2) significantly greater surrounding tissue damage in the higher energy dose groups; (3) a lower dose response in calcified tissue than in fatty streaks or fibrous atheroma; (4) immersion of tissue in blood during ablation resulted in a significantly greater dose response than immersion in plasma or saline, and the corresponding surrounding tissue damage was greatest under blood. Thus, argon laser light is both effective and predictable in response when ablating atheromatous tissue, and the efficiency of the process depends on the immersion medium. The degree of surrounding tissue damage depends on the energy dose.     

Pulsed Er:YAG- and 308 nm UV-excimer laser: an in vitro and in vivo study of skin-ablative effects

Using a pulsed XeCl excimer laser (308 nm) and a pulsed Er:YAG laser (2,940 nm), we investigated skin ablation as a function of pulse number, radiant energy, and repetition rate. In vitro analysis of lesions performed in freshly excised human skin were consistent with in vivo results obtained from experiments on pig skin. Pulsed 308 nm laser radiation caused considerable nonspecific thermal tissue injury followed by an inflammatory reaction and impaired healing of lesions in vivo. These findings were especially pronounced with higher repetition rates, which would be required for efficient destruction of larger lesions. On the other hand, the 2.94 microns Er:YAG laser radiation produced clean and precise lesions with only minimal adjacent injury. In vivo skin ablation caused intraoperative bleeding with deeper penetration. The Er:YAG laser offers a promising surgical tool for careful removal of superficial epidermal lesions, if higher repetition rates, and an appropriate laser beam delivery system are available for clinical use.     

In vitro Alexandrite laser angioplasty: A study on fibre conduction and tissue effects

Pulsed ultra-violet excimer laser radiation is capable of tissue ablation with only minimal thermal injury of adjacent tissue structures. Since difficult fibre optic coupling of energy was observed, alternative Q-switched laser sources capable of ablation of atherosclerotic plaque are under current investigation. To evaluate tissue effects of Alexandrite laser radiation, 160 arterial segments with macroscopic evidence of atherosclerotic disease were treated. The laser light was transmitted via silica based quartz fibres with different diameters. Using the Q-switched Alexandrite laser at the fundamental wavelength (748 nm) with a pulse duration of 300 ns the energy density threshold for tissue ablation was found to be in the range of 63 to 126 J cm^–2 using a 300m fibre. On macroscopic examination only limited thermal and acoustic injury was found in crater adjacent tissue structures. Crater edges were even and did not reveal signs of crater charring or debris in the crater lumen. However, the histological cross-sections revealed thermal injury extending from 100 up to 200m lateral into adjacent tissue. The crater margins revealed fissuring as a result of shock wave injury. Thermal damage was most evident if irradiation of atherosclerotic tissue was performed in blood.     

In vitro evaluation of ablation parameters of normal and fibrous aorta using smooth excimer laser coronary angioplasty

A modified exeimer laser energy delivery system was used to irradiate 100 segments of normal and fibrous aorta in vitro. The laser beam was scanned into 8 fiber bundles consisting of 50 fibers each resulting in a reduction of the applied pulse energy. The total repetition rate was increased to 150 Hz in order to keep the repetition rate per fiber bundle close to 20 Hz and to minimize thermal injury. The results demonstrate that effective ablation (etch rate per 8 pulses > 2.0 μm) occurred at an energy fluency of 50 mJ/mm² in both normal and fibrous aorta. Tissue damage (carbonization, tissue separation, fissures, cracks, and vacuolization) was in a range of 100 ± 28 to 152 ± 30 μm for normal aorta and in a range of 57 ± 35 to 110 ± 39 μm for fibrous aorta. We conclude that effective ablation of normal and fibrous human aorta can be achieved by the application of smooth excimer laser coronary angioplasty. This improvement of excimer laser technology may result in a reduction of shock wave- and cavitation-induced damage leading to a reduction of tissue injury. However, this awaits further in vitro and in vivo confirmation. © 1993 Wiley-Liss, Inc.     

Autofluorescence spectroscopy using a XeCl excimer laser system for simultaneous plaque ablation and fluorescence excitation

Laser–induced fluorescence may be used to guide laser ablation of atherosclerotic lesions. This study was performed to evaluate arterial autofluorescence spectroscopy in vitro using a single XeCl excimer laser (308 nm) for simultaneous tissue ablation and fluorescence excitation. The laser beam was coupled to a 600-μm silica fiber transmitting 40–50 mJ/mm² per pulse. The fluorescence radiation emanating retrogradely from the fiber was collected by a concave mirror for spectroscopic analysis over a range of 321–657 nm. The arterial media (n = 26), lipid plaques (n = 26), and calcified lesions (n = 27) of aortic specimens from ten human cadavers were investigated in air, saline, and blood. Whereas the spectrum of calcified lesions changed with the surrounding optical medium, the other spectra remained constant. In air and blood, the spectra of arterial media, lipid plaques, and calcified lesions could be differentiated qualitatively and quantitatively (P < 0.0001). In saline, there was no clearcut spectroscopic difference between lipid plaques and calcified lesions. However, normal arterial media and atherosclerotic lesions (lipid plaques plus calcified lesions) could still be discriminated. Thus spectroscopy and plaque ablation can be combined using a single XeCl excimer laser. These encouraging results should stimulate further studies to determine the potential use of this approach to guide laser angioplasty in humans. © 1994 Wiley-Liss, Inc.     

Excimer laser irradiation of non-calcified and calcified human atheroma (248 and 308nm wavelengths)

In order to develop a system of peripheral arterial angioplasty, we carried out an in vitro study to define the quantitative, thermal and morphological characteristics of human-atheroma ablation by excimer laser. A multigas ‘Sopra’ laser was used. The study was performed by using 248nm, krypton fluoride (KrF), then 308nm, xenon chloride (XeCl) wavelengths. The delivered energy was up to 150 mJ pulse⁻¹, pulse duration was 25ns, and the repetition rate could be adjusted to up to 20Hz. Irradiated tissue segments of the superficial femoral and external iliac arteries were obtained in man during surgical procedures and were both calcified and non-calcified atherosclerotic lesions. Quantitative measurements showed a linear increase of ablated tissue mass depending on the energy delivered. For the same energy, the loss of mass was greater with the 248nm wavelength than with the 308nm. The maximum temperature rise measured at the site of irradiation was 6°C at 248nm and 25°C at 308nm. Histological analysis of the irradiated segments revealed neat and precise ablation without thermal injury of adjacent tissue. At 248nm, this phenomenon was observed for calcified as well as non-calcified atheromas. It is concluded that quantitative, thermal and morphological characteristics of in vitro ablation of calcified and non-calcified human atheroma by excimer laser are compatible to clinical requirements. The results observed at 248nm were experimentally more satisfactory.     

Tissue interactions and measurement of ablation rates with ultraviolet and visible lasers in canine and human arteries

Ablation rates measured as the depth of tissue excavation per unit time were determined in human and canine aortas subjected to radiation with ultraviolet (UV) excimer (ArF 193 nm, KrF 248 nm, XeF 351 nm) and visible lasers [continuous wave (cw) and 50-ms chopped argon ion, 478 nm-514 nm; pulsed double-frequency Nd:YAG, 532 nm]. For UV and pulsed double-frequency Nd:YAG lasers ablation rates were constant in time and depended linearly on average laser power, but for cw and chopped argon lasers ablation rates varied with irradiation time and were nonlinearly dependent on laser power. In human aortas, atherosclerosis without gross calcification had no influence on ablation rates. Charring and tissue disruption were observed with cw and chopped argon ion, whereas excimer and pulsed Nd:YAG lasers produced only minimal injury to surrounding tissue. We conclude that the determination of ablation rates is useful for the selection of laser wavelengths and power densities applicable to angioplasty and that UV and pulsed visible laser permit a better control of ablation compared to continuous wave lasers.     

The role of pulse length in limiting distant damage to vascular tissue caused by the Nd-YAG laser

The total damage caused by equivalent doses of energy given to human cadaver vascular tissue over the same time scale from three Nd-YAG lasers of different pulse lengths is quantified. The continuous wave (c.w.) laser produces vacuolation and coagulation around a vaporized crater; the 100 μs pulsed laser produces less surrounding damage and the 10 ns pulsed laser none at all. The areas of damage in five craters made with 10 J energy were measured from histology slides using a digitising platten, and it was found that in each case the total amount of damage was the same, even though the depth of the craters made varied. The dose response for vaporization of the 10 ns pulsed laser was the greatest at 35 μm/J and that of the c.w. laser was least at 8 μm/J. A pulse length of 100 μs may not be the optimum for limiting surrounding tissue damage during laser angioplasty but it produces much less damage than a c.w. laser and unlike the 10 ns pulses is easily transmissible down an optical fibre.     

Responses of atherosclerotic aorta to argon laser

Lasers have been advocated to resect atherosclerotic plaques in the cardiovascular system, yet little information is available regarding the effects of laser on the range of occlusive lesions seen in the peripheral arterial tree. This study was conducted to assess the risk of perforation in human cadaveric aorta involved with variable degrees of atherosclerosis. Ten fresh segments of atherosclerotic human aorta were graded for extent of atherosclerosis, then subjected to argon laser energy within 48 hours. Using air as the conduction medium and with the fiber tip 2 or 5 mm from the vessel wall, the argon laser was applied to matched calcified and non-calcified arteries at 3.0-7.0 W and 10.0–13.5 W with energy density identical for matched pairs. Results were compared among segments which were normal in appearance or had only fatty streaks grossly with those with gross regional wall calcification. The mean penetration time (T) for calcified and non-calcified lesions at low and high power outputs was compared. Mean time to perforation and range of time necessary to produce perforation were greater in calcified than non-calcified segments at all power levels employed. These data suggest that atherosclerotic lesions vary in their response to argon laser. The presence of calcium may preclude resection of some plaques and protect against wall perforation.     

Excimer Laser Radiation for Endarterectomy of Experimental Atheromas

Open laser endarterectomy produces a smooth arterial surface with welded distal end points. This report evaluates 308-nm excimer laser radiation for the laser endarterectomy operation. Arteriosclerotic New Zealand white rabbits (N = 15) were studied. A thoraco-abdominal exploration was performed, the aorta was isolated, heparin was administered, and multiple endarterectomies were performed in each rabbit. A line of laser craters was created at the proximal and distal ends of an atheroma. Laser radiation was used 10 connect the craters to form the proximal and distal end points. The atheromas were dissected from the aorta with laser light and the end points were fused. The aortas were removed for light and electron microscopy and the animals were sacrificed. Excimer radiation was delivered by a 600-pm fiber at 50 rnJ/pulse, 120-ns pulses and either 15-or 20-Hz frequency. At 15 Hz excimer laser endarterectomies showed no perforations along the surface or at the end points. The surfaces were smooth but the end points were not welded in place. At 20 Hz, perforations were seen along 7/11 surfaces and at 5/11 end points. Excimer laser endarterectomy is best performed at 15 Hz. The end points, however, cannot be welded with excimer laser radiation.     

Thermal side effects of fiber-guided XeCl excimer laser drilling of cartilage

We examined thermal effects during ablation of human joint cartilage using two XeCl excimer lasers with pulse durations of ～ 20 ns and 60 ns. An increase in radiant exposure or repetition rate caused a rise in tissue temperature up to 82°C at a 100- μm distance. With increasing distance from the crater edge, the temperature dropped exponentially. Radiant exposures higher than 1.8 J/cm² and repetition rates above 20 Hz lead to a formation of hot gaseous products escaping from the laser crater. When os-teoarthritic cartilage is irradiated, these gases spread inside the tissue causing a temperature rise of > 50°C at a distance of 1 mm from the crater edge. In the contact mode, we found a linear rise of ablation rate with increasing repetition rate both in air or saline. But ablation rates in saline were only half the rates achieved in air. Both phenomenons can be explained by additional thermal effects of excimer lasers working in the range of higher repetition rates and pulse energies. © 1994 Wiley-Liss, Inc.     

Effect of force on ablation depth for a XeCl excimer laser beam delivered by an optical fiber in contact with arterial tissue under saline.

The effect of force applied to a 430 micron single fiber, delivering 60 pulses of 308 nm XeCl laser radiation at 20 Hz, on the ablation depth in porcine aortic tissue under saline has been investigated. Energy densities of 8, 15, 25, 28, 31, 37, and 45 mJ/mm2 were used. Force was applied by adding weights from 0 to 10 grams to the fiber. The fiber penetration was monitored by means of a position transducer. At 0 grams, the ablation depth increased linearly with incident energy density, but the fiber did not penetrate the tissue; with any weight added, the fiber penetrated the tissue at energy densities above 15 mJ/mm2. The fiber did not penetrate during the first several pulses, possibly due to gas trapped under the fiber. After these first pulses, a smooth linear advancement of the fiber began, which lasted until the pulse train stopped. The ablation depth increased with increasing energy densities and weights. This effect was largest above 25 mJ/mm2 where the ablation efficiencies (unit mm3/J), with weights added to the fiber, were substantially larger than values found in 308 nm ablation experiments described in the literature, which were conducted with either a focused laser beam or a fiber without additional force. The results imply that in 308 nm excimer laser angioplasty, force must be applied to the beam delivery catheter for efficient recanalization, and that experiments performed with a focused beam or without actual penetration of the fiber do not represent the situation encountered in excimer laser angioplasty.     

Cardiovascular Laser Application

With the invention of the laser, many clinical disciplines have taken advantage of this new energy source. Its precision, intensity and energy density is superior to all other known surgical devices. Based on the principle of light amplification from a photon-emitting resonator, the monochromaticity, collimation and coherence provide the high-energy density of the laser beam for medical applications. The state-of-the-art and future potential of laser use in cardiovascular diseases will be reviewed. Most of the work in this field has been accomplished during the past decade with numerous research projects. Although many technical advances have been made, so far the results in cardiovascular medicine are in the areas of vessel anastomosis, ablation of conduction passes for arrhythmia therapy, and angioplasty. In this paper, special attention will be given to the recent success in XeCl excimer laser application for photodecomposition of tissue with a goal of improved recanalization. The high-power density of the XeCl excimer laser provides significant advantages for the disruption of both embolic and calcified plaque. Regardless of the type of tissue ablated, gross, histologic, and ultra-structural analysis confirmed the absence of thermal injury in luminar recanalization as well as in animal studies. Progress in the manufacture of catheters, with multiple very small diameter fibers, led to the decisive breakthrough in clinical laser angioplasty. Peripheral as well as coronary arteries have been successfully recanalized followed by balloon dilatation. The ease of application and the success achieved thus far have resulted in an optimistic assessment for laser medicine.     

Excimer laser ablation of fibrocartilage: an in vitro and in vivo study

To date, lasers have found only limited applications in orthopedics. We employed a 308 nm XeCl excimer laser for ablation of fibrocartilage, in order to investigate the feasibility of excimer laser assisted meniscectomy. Experiments were conducted both in vitro and in vivo. For the in vitro study, human menisci, obtained during surgery and autopsy, were irradiated via a 600 microns core fiber at radiant exposures ranging between 20 mj/mm2 and 80 mj/mm2, at 20 Hz. Ablation rate measurements and histological analysis of the samples were performed. The ablation rates were found to range from 3 microns/pulse to 100 microns/pulse depending on the radiant exposure and/or the applied pressure on the fiber delivery system. Thermographic analysis was also performed during pulsed excimer as well as CW Nd:Yag and CW CO2 laser irradiation. Temperatures were lower for excimer laser (Tmax less than 65 degrees) than CW ND: Yag (Tmax less than 210 degrees) or CW CO2 (Tmax less than 202 degrees) laser. For the in vitro study, medial meniscectomy was performed in 15 rabbits with the excimer laser and a CW Nd:Yag laser in the right and left knee respectively. Excimer laser irradiation was performed at 70 mj/mm2. Nd:Yag irradiation was performed via a 600 microns core fiber at power outputs between 20 to 40 W for 10 and 20 seconds duration. The healing response to injury was investigated by histological analysis of the menisci after 1 day, 1, 2, 4, and 8 weeks following the laser procedure. Excimer laser treated menisci showed less inflammatory reaction and noticeable repair with minimal inflammatory response.(ABSTRACT TRUNCATED AT 250 WORDS)