Vascular contractile function following experimental excimer laser angioplasty

The aim of this study was to determine the vasomotor response to in vivo excimer laser irradiation with regard to laser-induced tissue effects. Transfemoral excimer laser angioplasty was performed in the right carotid artery of 11 New Zealand white rabbits. In four additional rabbits (sham group), the procedure was performed without the application of laser energy. Angiography documented vessel dissection in five laser-treated animals. Perforation occurred in one animal. Rings of the treated artery and controls of the contralateral artery were investigated in a contraction chamber. The passive stress-strain relation (PSS) and the maximum contraction force (MCF) after stimulation with noradrenaline, serotonin and potassium chloride were determined. The treated vessels had a higher PSS than the control (p=0.05). The MCF was lower in the treated vessels (p<0.05). The contraction force of the sham-operated vessels was higher, although statistically not significant, compared to the laser-irradiated segments. In a subset analysis, performed to compare vessels with moderate and severe trauma, MCF was significantly reduced in vessels with severe laser-induced injury. Experimental in vivo excimer laser angioplasty in this model resulted in heterogeneous structural changes, including dissections and perforation. Post-mortem assessment of vasomotor response showed no significant difference between laser-treated and sham-operated animals. However, the contractile function of the target vessel seems to be reduced following extensive laser-induced vessel injury.     

Experimental study of application of excimer laser to laser angioplasty

The possible application of excimer laser to laser angioplasty was studied. In the first experiment, the ablative effects of excimer laser at wavelengths of 248 nm and 308 nm on the pig myocardium were examined in vitro at an air-tissue interface. Crater depth increased with total delivered energy and energy per pulse. Very clear cuts could be observed by histological examination. There was no evidence of thermal damage at a wavelength of 248 nm, at 10 pps. Above 10 pps, a thin bordering zone of suspicious thermal damage was noted with the wavelengths of 248 nm and 308 nm. Thermal damage increased with pulse repetition rate. In the second experiment, the effects of excimer laser irradiation on blood were examined. Five vials, each of which contained 3 ml of blood, were exposed to 37.5 mJ laser beam at 10 pps in repetition rate for 10, 20, 30, 40, 50 seconds. One vial was left untreated as a control. No change in hematocrit value was observed after excimer laser irradiation. In contrast, the level of plasma free hemoglobin rose progressively with each increased duration of exposure. This result indicates that the lysis of erythrocytes does not occur in the laser-exposed cells. However, the damage to erythrocyte membrane took place as it was evidenced by progressive hemoglobin leakage into plasma. In the third experiment, the excimer laser was coupled to a 400 microns quartz optical fiber and the laser energy transmitted through the fiber was measured. At a wavelength of 308 nm, pulse energies up to 9 mJ were noted at the tip of the fiber. At a wavelength of 248 nm, the fiber tip was destroyed. In the fourth experiment, acute and chronic healing responses of normal canine arteries to excimer laser irradiation were studied in 4 mongrel dogs. The artery healed completely at the 18th day after the excimer laser irradiation. There was no evidence of thrombus formation and intimal hyperplasia in these arteries. The results suggest the applicability of excimer laser to laser angioplasty.     

Pulsed excimer laser angioplasty of human cadaveric arteries

Laser angioplasty has been limited by the lack of precise control of thermal and acoustic vascular injury. Pulsed excimer lasers, by contrast, have a capacity to affect target tissue without heat dispersion or damage to surrounding structures. The ablative properties of three excimer wavelengths, krypton fluoride (249 nm), xenon chloride (308 nm), and xenon fluoride (351 nm), were investigated with the use of fresh human cadaveric normal and atherosclerotic femoral arteries. Light and electron microscopy demonstrated clean cuts with histologically normal edges. There was no evidence of either thermal or acoustic damage with any of the wavelengths studied. The depth of ablation varied directly with the number of pulses and inversely with tissue density while the incision width remained constant. The excimer laser appears to offer significant advantages over its conventional counterparts for the ablation of atherosclerotic plaque.     

Percutaneous, in vivo excimer laser angioplasty: results in two experimental animal models

Pulsed ultraviolet light from an excimer laser was successfully transmitted via conventional fused silica optical fibers and used to accomplish recanalization of stenotic or totally occluded arteries in an intact, flowing blood field of two atherosclerotic animal models. The fibers, 300-600 micron in diameter, were delivered percutaneously in wire-guided multilumen catheters and then used to transmit wavelengths of 308 or 351 nm from excimer lasers with pulse durations of 12 nsec or less. Lesions from 70-100% diameter narrowing, and 0.6 to 5.5 cm in length were successfully recanalized (less than 50% residual diameter narrowing) in eight animals, using 3-4 J/cm2/pulse, 10-50 Hz, and 48-370-sec cumulative exposure. Necropsy examination in six of the eight animals disclosed no signs of thermal injury. Perforations were observed in four of eight animals. Thus, while use of an excimer laser power source did not obviate vascular perforation as a complication of laser angioplasty, these preliminary results indicate that energies of pulsed ultraviolet light sufficient to ablate atherosclerotic plaque can be both transmitted via conventional fused silica optical fibers and used successfully within an intact, flowing blood field. It may therefore be possible to use pulsed ultraviolet light from an excimer laser to accomplish percutaneous ablation of atherosclerotic arterial obstructions in humans.     

Next generation catheters for excimer laser coronary angioplasty

. In response to the need for maximising debulking in complex lesions, three new excimer laser coronary angioplasty catheter designs have been introduced. The eccentric laser catheter features a fibreoptic bundle disposed opposite the guide-wire lumen at the catheter tip and a torque mechanism that allows the user to rotate the fibre bundle toward the lesion mass. Residual lumens 50% larger than the catheter tip diameter have been obtained when multiple passes were made, with each pass performed using a different tip rotation. A recent case series utilising this catheter in restenosed stents resulted in larger lumens and lower 6-month restenosis rates. The optimal spaced (OS) laser catheter features a fibre bundle placed concentrically around the guide-wire lumen. The 61 μm diameter core fibres are spaced at a nominal centre-to-centre distance of 90 μm, resulting in a 40% increase in ablative area as compared to previous concentric catheter designs. In vitro testing and clinical evaluation demonstrated OS catheters routinely achieve an ablated area ≥90% of the catheter tip size. The 0.9 mm catheter features a high-density fibre pack composed of 65 fibres. Peripheral dead space has been minimised to maximise penetration of calcified plaque. When combined with laser parameters of up to 80 mJ/mm², and 80 Hz pulse repetition rate, the catheter demonstrated improved hard tissue and calcified tissue penetration in vitro. Clinical evaluation in Canada revealed a 94% lesion recanalisation rate in high-grade stenoses with angiographic evidence of calcification, chronic total occlusions, and lesions which have failed balloon angioplasty.     

Application of excimer laser angioplasty in acute myocardial infarction

BACKGROUND AND OBJECTIVE: Patients presenting with acute myocardial infarction who fail to respond to standard therapy with thrombolytics or have contraindications for their use oftentimes need revascularization with a mechanical device for removal of an occlusive coronary thrombus and its underlying atherosclerotic plaque. As both thrombi and plaques absorb laser energy in the ultraviolet wavelength (308 nm), we studied the feasibility and safety of excimer laser angioplasty in selective patients with complicated acute myocardial infarction. STUDY DESIGN/MATERIALS AND METHODS: Fifty patients with acute myocardial infarction complicated by continuous chest pain and/or ischemia who had a total of 54 obstructive lesions were treated with percutaneous excimer coronary laser angioplasty (ELCA). A Q-wave myocardial infarction was documented in 56% and a non-Q-wave myocardial infarction in 44%. The baseline left ventricular ejection fraction was reduced at 43 +/- 13% and six patients (12%) presented to the cardiac catheterization laboratory in cardiogenic shock. Twenty-nine patients failed to respond to thrombolytic therapy and 16 had contraindications for thrombolytics and IIb/IIIa receptor antagonists. Following laser debulking, all patients received adjunct balloon dilation and then stents were deployed in 83% of the target lesions. Quantitative coronary arteriography (QCA) was performed at an independent core laboratory. RESULTS: Ninety-eight percent laser success and 100% procedural success were achieved. By QCA the minimal luminal diameter increased from baseline of 0.7 +/- 0.5 to 1.3 +/- 0.5 mm post-lasing and then to 2.0 +/- 0.6 with balloon dilation to a final of 3.0 +/- 0.5 mm. Pre-laser percent stenosis diameter of 77 +/- 17% was reduced to 51 +/- 22% post-laser to 3.0 +/- 17% post-balloon and to a final of 15 +/- 25%. An 83% laser-induced reduction of thrombus burden area was achieved as well as an increase in TIMI flow from baseline of 1.7 +/- 1.1 to 2.8 +/- 0.4 by laser to a 2.9 +/- 0.4 final. There were no deaths, emergency bypass surgery, cerebral vascular accident, neurologic injury, or major perforation. In one case, a laser-induced major dissection was successfully treated by stenting. All 50 patients survived the procedure, improved clinically, and were discharged. CONCLUSION: Application of excimer laser coronary angioplasty is feasible and safe in selected patients with acute myocardial infarction who either fail to respond to thrombolytics or have contraindications to these agents. Intracoronary thrombus at the target lesion can be successfully dissolved with this wavelength laser energy without adverse effect on the procedure results.     

Smooth excimer laser coronary angioplasty (SELCA) and conventional excimer laser angioplasty: Comparison of vascular injury and smooth muscle cell proliferation

Although the excimer laser, which utilizes ‘non-thermal ablation effects’, has achieved encouraging results in early clinical trials, the long-term results have failed to show any advantage over conventional percutaneous transluminal coronary angioplasty (PTCA). A new system, Smooth Excimer Laser Coronary Angioplasty (SELCA), has been developed to reduce the tissue damage in the vessel wall caused by shock waves and vapour bubbles.SELCA (wavelength 308 nm, pulse duration 115 ns, repetition rate 150 Hz and energy density 50 mJ mm^-2) lowers the amount of shock wave formation and pressure peak amplitude in the surrounding tissue by about eight times when compared to the conventional 308 nm excimer laser (ELCA). In this preclinical evaluation, this new system was compared to ELCA. Fifty New Zealand White rabbits were stimulated by repeated weak DC impulses for a period of 28 days in order to form an atherosclerotic plaque in the right carotid artery. The vessels were excised 3, 7,14 and 28 days after laser irradiation for immunohistochemical analysis. SELCA and ELCA laser treatment lead to a decrease in maximal intimal wall thickness 3 days after intervention (control: 177±4 μm; SELCA: 131±22μm; ELCA: 120 ±33μm). In the period between 3 and 28 days, a moderate increase in intimal wall thickness was observed after SELCA treatment compared to a significant increase after ELCA (28 days after intervention: SELCA: 157±22μm; ELCA: 274 ±28μm). Bromodeoxyuridine (BrdU) was applied 18 and 12 h before excision of the vessels in order to determine the percent of cells undergoing DNA synthesis. The percent of BrdU labelled SMC in the intima (control: 13 ± 2 cells mm_-2) increased in both groups after 3 days (SELCA: 248 ± 107 cells mm^-2; ELCA: 162 ± 41 cells mm^-2) and 7 days (SELCA: 162± 55 cells mm^-2; ELCA: 279 ± 119 cells mm^-2). The present results demonstrate that vascular wall injury and increase in intimal wall thickness following SELCA are reduced in comparison to the results achieved with the conventional technique. Further trials are necessary to assess whether these improvements will lead to more favourable long-term results after excimer laser angioplasty.     

Coronary revascularization in heart transplant recipients by excimer laser angioplasty

BACKGROUND AND OBJECTIVE: Aggressive development of allograft coronary artery disease is a major cause of death in heart transplant recipients. Percutaneous balloon angioplasty is considered suboptimal for complex lesions in native coronary vessels and heart transplant recipients, alike. Excimer laser energy (308-nm wavelength) can successfully remove and vaporize atherosclerotic plaques in native coronary vessels; however, its application in heart transplant recipients has not been studied clinically yet. STUDY DESIGN/MATERIALS AND METHODS: Six heart transplant recipients underwent percutaneous excimer laser (CVX-300, Spectranetics, Colorado Springs, CO) coronary angioplasty for treatment of a total of 10 discrete, obstructive coronary artery lesions. By using concentric or eccentric multifiber laser catheters, energy parameters were set at a fluence of 45 mJ/mm(2) or 60 mJ/mm(2) with a frequency of 25 Hz and 40 Hz, respectively, with a pulse duration of 135 ns and output of 200 mJ/pulse. The "saline flush" and "pulse and retreat" lasing techniques were used. In each case, adjunct balloon angioplasty was performed; in five lesions, an intracoronary stent was implanted. Angiographic evaluation was performed by visual assessment. RESULTS: Each procedure was successful as defined by laser recanalization of the target lesion (reduction of target lesion stenosis in more than 20%) and subsequent adequate final luminal patency (reduction of target lesion stenosis to less than 50%) and absence of any major in-cardiac catheterization complication (such as perforation, acute closure, dissection, emergency coronary artery bypass surgery), or in-hospital complications (such as death, myocardial infarction, cardiac enzyme elevation, major bleeding), or need for surgical revascularization. A 92 +/- 5% preprocedural percent diameter stenosis was reduced by laser to 35 +/- 16% and by adjunct balloon angioplasty in all lesions and stenting in five lesions, to final residual stenosis of 2 +/- 6%. Angiographic follow-up between 2 and 6 months after the procedure demonstrated a target lesion restenosis rate of 22%. CONCLUSION: Percutaneous excimer laser is safe and efficacious in the treatment of focal obstructive lesions caused by allograft coronary artery disease. These data represent an early clinical experience; thus, the long-term outcome of this revascularization method in recipients of heart transplantation will have to be determined by a large scale prospective, randomized, multicenter clinical study.     

Catheter associated problems of multi-fibre systems in clinical excimer laser angioplasty

We report our experience in 60 patients using a recently designed 4 French ring catheter system for coronary and a 7 French ring catheter for peripheral percutaneous excimer laser angioplasty. The advantages in comparison to bare fibres comprise an improved flexibility and a central channel for insertion of guide wires to minimize the risk of mechanical vessel wall perforation. The peripheral laser catheter initially transmitted overall energies of 20 mJ pulse^–1 (51 mJ pulse^–1 mm^–2), the coronary device 4.5–5 mJ pulse^–1 (32 mJ pulse^–1 mm^–2). A 50% or more decrease of energy transmission was found in 43% of coronary catheters due to a number of blinded fibres with other fibres remaining intact. This was either due to a retrograde expansion of shock waves generated by the excimer pulse at a calcified lesion, or the result of a deleterious back-reflection of the laser light by contrast media. However, using both laser catheters ablation of plaque in vivo proved to be possible. Small mechanical defects of the catheter tips in 27% did not result in patient related complications. Our initial experience favours further improvement of ring catheters for percutaneous excimer laser angioplasty.     

Initial clinical experience with a modified excimer laser for coronary angioplasty

A clinical study was conducted in 32 patients to evaluate the efficacy and safety of a modified excimer laser system for percutaneous transluminal coronary angioplasty. In this system, the laser beam is scanned and transmitted into eight fibre bundles of the catheter device, consisting of 20 50 μm fibres, each. Twenty-eight patients were treated with 1.5 mm laser catheters, four patients with 1.8 mm laser catheters. Mean time of energy delivery was 82±39 s using a mean energy fluence of 49±2 mJ mm⁻². In all 32 patients in whom laser angioplasty was attempted, laser irradiation resulted in a stenosis reduction from 85±10% (mean±s.d.) before to 57±20% after laser treatment. In 16 patients, additional balloon angioplasty had to be performed, either due to an insufficient angiographic result in 11 patients or due to abrupt vessel closure in five patients. In these 16 patients, percent stenosis decreased after balloon angioplasty to 35±14%, corresponding to a luminal diameter of 1.6±0.5 mm. In 10 patients, dissection was observed. In one of these patients, the dissection resulted in a reduction in antegrade flow, necessitating balloon dilatation. One perforation occurred which did not require surgery. There were no deaths, bypass surgery or myocardial infarction. During the time of follow-up, restenosis occurred in 14 patients; in two of these patients bypass surgery was performed and five patients were treated with conventional balloon angioplasty. These results suggest that this form of modified excimer energy delivery provides effective therapy for patients with coronary artery disease. Due to the small catheter sizes, however, one-half of the patients still required additional balloon dilatation. To increase the number of stand-alone laser procedures and to address the issue of restenosis in this patient population appropriately, larger catheter devices will be necessary.     

Application of excimer laser coronary angioplasty (ELCA) in bifurcation lesions

. Excimer laser coronary angioplasty (ELCA) offers a unique approach to the treatment of bifurcation lesions that continues to present a challenge in percutaneous coronary intervention. Debulking plaque prior to stenting or balloon angioplasty has demonstrated significant improvement in the treatment of bifurcation lesions. Clot dissipation properties of excimer laser combined with its ability to debulk, makes this device unique when applied to thrombus-laden bifurcation lesions. ELCA is the only debulking technique that allows retention of two guide wires with resultant protection of the bifurcation vessels during the debulking procedure. We herein describe three patients with unstable angina who underwent a debulking procedure with ELCA involving application of single and double wire techniques. These three cases illustrate two different techniques used for debulking bifurcation lesions. Both single and double wire techniques are described. ELCA can be used safely and effectively in high-risk patients with bifurcation lesions, even in the presence of thrombus.     

Percutaneous transluminal excimer laser angioplasty in total peripheral artery occlusion in man

Laser angioplasty and laser-assisted angioplasty have become a clinical reality. Producing sharply defined borders of the ablated area with minimal adjacent thermal damage, excimer lasers offer several proven and some potential advantages over conventional systems. To evaluate the feasibility of excimer laser angioplasty, we have treated one patient using 308-nm radiation via a bare fiber in direct contact with the total occlusion of a right femoral artery. The lesion was successfully recanalized, thus allowing easy passage of the balloon catheter and subsequent dilatation. This percutaneous laser recanalization of an occluded peripheral artery is one of the first to be done in man using excimer laser radiation, thus demonstrating that the technique is feasible and the system is potentially useful.     

Endovascular treatment of in-stent restenosis using excimer laser angioplasty and drug eluting balloons

In-stent restenosis after endovascular treatment of stenotic and occlusive disease of the infrainguinal arteries is still a clinical challenge. In this paper an overview of the current status of drug-eluting balloon technology and results of clinical trials with drug-eluting balloon angioplasty is given. Furthermore a case series of 10 patients with in-stent restenosis that were treated with excimer laser angioplasty and drug eluting balloons is described. In this case series the mean lesion length treated was 115 mm, and the mean time to occurrence of restenosis after initial treatment was 7.2 months. At a mean follow-up (of all patients) of 7.6 months no target vessel revascularization was seen. In 7 patients that had Duplex and/or angiographic control (mean follow-up 7 months) no signs of neointimal hyperplasia were demonstrated. These short-term data compare favorable to results obtained with standard balloon angioplasty and cutting-balloon angioplasty. Long-term follow-up is necessary to define the role of combined excimer laser and drug-eluting balloon angioplasty in the treatment of in-stent restenosis further.     

间甲酚化学烧伤实验性治疗

目的 开展间甲酚化学烧伤动物实验研究，为临床治疗提供理论依据。方法 将间甲酚原液涂在家兔背部，并随机分为对照、手术切痂、ＳＤ－Ａｇ涂药、饱和硫酸钠湿敷及自来水冲洗组。检测血液中ＢＵＮ、ＡＬＴ、ＡＳＴ、ＧＧＴ、ＡＫＰ５种生化指标。观察心、肝、脑、肺、肾的病理变化及超微结构变化。结果 间甲酚不仅可对皮肤造成深度烧伤，而且经过皮肤渗透还可引起全身主要脏器的４种不同治疗方法均有效，其中以手术切痂、外涂ＳＤ     

Improved results of coronary excimer laser angioplasty by the use of advanced transmission devices

Excimer laser angioplasty is an alternative method for the treatment of obstructive coronary lesions. Initial clinical results demonstrated the safety and feasibility of the procedure. However, efficacy was limited by low catheter flexibility and unreliable energy transmission. Advanced transmission devices were used in 80 interventions in 79 patients. The catheter diameter is 1.3, 1.5 or 1.8 mm, the catheters consist of 20, 30 or 35 quartz fibres (100 m) respectively. The mean energy density was 55 ±18 mJ mm^–2, mean loss of energy transmission was 20%. The pulse width was 60 ns and 115 ns in 40 interventions each. The target vessel was the LAD in 53, the LCX in 6 and the RCA in 21 interventions.Failure of laser angioplasty occurred in 10 patients due to failed guidewire placement (N=6), failed catheter placement (N=3) or impossibility to cross the lesion with the catheter (N=1). Stand-alone laser angioplasty was performed in 43/70 procedures. Additional balloon angioplasty was necessary due to an unsatisfactory result (N=10) or due to complications (N=17) in 27 patients. Vessel occlusion occurred in 18 patients (25%) and could be successfully resolved by balloon dilatation (N=16) or additional laser angioplasty (N=1) in 17 patients. Two early occlusions were found at the 24-h control angiography. The incidence of myocardial infarction and in-hospital death (N=1) was 1.4%.Conclusion: The use of an advanced energy delivery system with trusted energy transmission and higher energy density increased the primary success rate of stand-alone excimer laser angioplasty. However, further improvement of catheter flexibility and reduction of dead space at the catheter tip is necessary to optimize ablation efficacy.     

Clinicopathologic study of healing excimer laser radial excisions

Four radial linear excisions were created by an argon fluoride (193 nm) excimer laser in the edematous cornea of a blind eye of a diabetic human patient. Partial thickness corneal trephinations were performed at 3, 7, and 18 months after surgery for histopathologic examination. At 3 months, a wide gap in Bowman's layer permitted extension of an epithelial plug to a depth of 0.35 mm; at 7 and 18 months, the depth of the epithelial plug was decreased to 0.29 mm and 0.01 mm, respectively. With wound healing, excision width decreased and the two cut ends of Bowman's layer were almost reapposed by 18 months, suggesting wound contraction. Linear excisions with the excimer laser appear to be wider than incisions made with a diamond blade, but the pattern of wound maturation appears to be similar.