Analysis of photoproducts, free radicals, and particulate debris generated during in vivo argon laser myoplasty.

Catheter-guided laser myoplasty in a closed ventricle has been advocated for the treatment of hypertrophic cardiomyopathy, ablation of arrhythmogenic foci, and transmyocardial laser revascularization of ungraftable regions of ischemic myocardium. The purpose of this study was to evaluate the nature of particulate debris and photoproducts generated in vivo. Accordingly, cardiopulmonary bypass was established in four dogs without active cooling and an apical left ventricular vent was placed. In two dogs, a laser catheter was inserted into the cardioplegia-arrested left ventricle through the left atrial appendage and across the mitral valve. In the other two dogs the laser catheter was inserted into a perfused, fibrillating left ventricle retrograde across the aortic valve. Myocardial ablation of the ventricular septum was performed using continuous argon-ion laser irradiation (8-10 watts, 4-11 minutes) and blood samples were drawn through the ventricular vent. The final ablation in each dog was done during a separate ventricular flush with a chemical "spin trap" capable of detecting free radicals. Analysis of ventricular effluent revealed levels of carboxyhemoglobin and hydrogen cyanide which were well below accepted clinical toxic limits. Microparticulate debris (2-300 femtoliter) was not detected. Evidence of trace free radical generation was suggested in one of four dogs. In conclusion, closed ventricular argon laser myoplasty did not generate clinically significant levels of the toxic photoproducts we measured, or microparticulate debris. These in vivo findings suggest that the clinical application of catheter-based laser myoplasty will not be limited by the generation of these toxic photoproducts or microembolic debris.

Atherosclerotic Yucatan microswine: an animal model with high-grade, fibrocalcific, nonfatty lesions suitable for testing catheter-based interventions.

A new breed of swine, the Yucatan microswine, that was derived from repetitive inbreeding of selected, small Yucatan swine, was investigated as an animal model of advanced vascular atherosclerosis. Nineteen animals were fed an atherogenic diet for 9.9 +/- 1.5 (mean +/- SEM) weeks before and 19.9 +/- 1.8 weeks after balloon endothelial denudation of all four iliac arteries. In 18 (94.7%) of the 19 microswine, angiography performed at 33 to 87 weeks of age disclosed some degree of luminal diameter narrowing: six animals (33.3%) had one-vessel, six (33.3%) had two-vessel, four (22.2%) had three-vessel, and two (11.1%) had four-vessel disease. In 38 (50%) of 76 denuded arteries, angiographically apparent luminal diameter narrowing was observed as follows: three arteries (7.9%) were narrowed less than 50%; 10 arteries (26.3%) were narrowed 50% to 75%; seven arteries (18.4%) were narrowed 76% to 99%; and 18 arteries (47.3%) were occluded. Sixty-four arteries were harvested from 16 of the 18 microswine with angiographically apparent luminal narrowing, which yielded 748 histologic sections. Maximum cross-sectional area narrowing from atherosclerotic plaque exceeded 90% in 135 (18%) of the sections examined, while 65 sections (9%) were narrowed 76% to 90%, and 127 sections (17%) were narrowed 51% to 75%. Atherosclerotic plaque in these animals appeared histologically similar to the so-called "complex" lesion that is typical of human atherosclerosis, which consists predominantly of collagen with focal calcific deposits and a minor lipid component. The smaller size and lower weight of these animals, in comparison with full-size farm pigs and "minipigs," facilitated transportation, handling, and instrumentation. These findings establish the Yucatan microswine as a useful, representative, and economical atherosclerotic animal model for the evaluation of novel interventional techniques.

Vascular spasm complicates continuous wave but not pulsed laser irradiation.

Preliminary clinical experience with laser angioplasty has suggested that arterial spasm may complicate attempts to employ laser light to accomplish vascular recanalization. The present study was designed to investigate the role of energy profile on the development of arterial spasm during laser angioplasty. Laser irradiation was delivered percutaneously in vivo to New Zealand white rabbits and to Yucatan microswine with or without atherosclerotic lesions induced by a combination of balloon endothelial denudation and atherogenic diet. Continuous wave (CW) laser irradiation from an argon ion gas laser (wavelength 488 to 514 nm) was applied to 23 arteries, while 16 arteries were irradiated using a pulsed xenon chloride (308 nm) or xenon fluoride (351 nm) excimer laser. Arterial spasm, defined as greater than 50% reduction in luminal diameter narrowing, complicated delivery of laser light to 17 (74%) of the 23 arteries irradiated with the CW argon laser. Spasm was consistently observed at powers greater than 2 W, at cumulative exposures greater than 200 seconds, and at total energy greater than 200 joules. Spasm was typically diffuse (including the length of the vessel) and protracted (lasting up to 120 minutes). Intra-arterial nitroglycerin (up to 300 micrograms) produced only temporary and incomplete resolution of laser-induced spasm. In contrast, spasm was never observed in any of the 16 arteries in which laser angioplasty was performed using a pulsed laser (0.95 to 6.37 joules/cm2, 10 to 50 Hz, 48 to 370 seconds). Thus CW but not pulsed laser angioplasty may be complicated by arterial spasm.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effects of continuous laser on arterial vasomotoricity in vitro]. / Effets du laser continu sur la vasomotricité artérielle in vitro.

The effects of a continuous-wave argon laser irradiation on arterial vasomotricity were studied isometrically on 19 aortic segments obtained from rabbits. The segments had a resting tension of 1 g and were suspended in a perfusion chamber filled with a Krebs-bicarbonate buffer solution at 37 degrees C gassed with 95 p. 100 O2 and 5 p. 100 CO2. Irradiation was performed with an argon laser emitting principally at 488-514 nm, via a flexible optical fibre 200 microns in diameter. The tension of each specimen, measured with a strain gauge, was recorded at the same time as the arterial wall temperature, measured by a thermistor probe. The integrity of the endothelium was checked by scanning electron microscopy and acetylcholine test. The endothelium of 5 specimens was deliberately abrased, and this was checked by the same methods. Laser irradiations of more than 1 watt regularly (n = 34) induced a contraction the kinetics of which were parallel to those of the arterial wall heating and usually reversible after the end of irradiation. With irradiations of less than 0.1 watt, the parietal temperature never rose by more than 5 degrees C, and the vasomotor response always (n = 41) was a relaxation which was reversible after irradiation. At intermediate levels of power, the vasomotor response was biphasic and of low amplitude (n = 100). At all levels, similar responses were given by specimens whose endothelium had been removed. Thus, at the powers used for angioplasty, irradiation of the arterial wall by continuous-wave argon laser induces and intense vasoconstriction which is independent of the endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulsed ultraviolet laser irradiation produces endothelium-independent relaxation of vascular smooth muscle.

Recent studies have shown that continuous wave laser irradiation induces contraction of vascular smooth muscle, except at powers far below the threshold for tissue ablation. To determine the corresponding effects of pulsed laser irradiation on vascular smooth muscle tone, vascular rings of rabbit thoracic aorta were mounted isometrically with 1 g tension in Krebs-bicarbonate buffer and irradiated with 308 or 351 nm from an excimer laser through a 400-microns optical fiber. A total of 250 exposures were performed with 1-6.5 mJ/pulse (fluence = 0.8-5.5 J/cm2), 10-50 Hz, and cumulative exposures of 10-120 seconds. Excimer laser irradiation in combinations of pulse energy (PE), repetition rate (RR), and cumulative exposure below, at, or above threshold for tissue ablation consistently produced relaxation unassociated with contraction in each of the 250 exposures. For the total 250 exposures, the magnitude of relaxation (reduction in recorded tension, Rmax) was 55 +/- 4% (mean +/- SEM) of maximum vasomotor reactivity recorded in the specimen in response to administration of serotonin. Rmax varied directly with both PE and RR. When PE was increased from 1 to 5 mJ/pulse (n = 13), Rmax increased from 57 +/- 19% to 80 +/- 19% (p less than 0.0001); when RR was increased from 10 to 50 Hz (n = 10), Rmax increased from 27 +/- 8 to 46 +/- 8 (p less than 0.0001). Rmax varied independently of endothelial integrity (assessed anatomically and pharmacologically) and wavelength (308 vs. 351 nm). Simultaneously recorded tissue-temperature profiles disclosed that during pulsed laser irradiation, tissue temperature rise did not exceed 5 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

[Effect of pulsed excimer laser on arterial smooth muscle]. / Effet du laser pulsé à excimères sur le muscle lisse artériel.

The effect of pulsed lasers on vasomotricity was measured on 22 segments of isolated rabbit thoracic aorta. The segments were isometrically suspended in a bath of Krebs-bicarbonate buffer and irradiated with two excimer lasers (XeCl and XeF) emitting at 308 and 351 nm respectively and coupled with a 400 mu optical fibre. The 10 to 120 seconds irradiations were performed at frequencies ranging from 10 to 100 Hz and pulse energies comprised between 1 and 7 mJ. These parameters were on both sides of the tissue ablation threshold. On the 22 segments studied the irradiation induced in every case (n = 118) relaxation of the vascular smooth muscle. The presence or absence of an anatomically and functionally intact endothelium was checked by scanning electron microscopy and by induction of relaxation with acetylcholine. Identical results were observed on specimens that had been subjected to deliberate endothelial abrasion. Relaxation was increased by drug-induced precontraction. The rise in arterial wall temperature, as measured by thermistor microprobe, never exceeded 5 degrees C, and histological examination of the specimens never showed thermal damage. It is concluded that on the isolated rabbit aorta pulsed excimer laser irradiation induces an endothelium-independent smooth muscle relaxation most probably due to photorelaxation combined with a lack of significant heating of the arterial wall. These experimental data support the use of pulsed sources for laser angioplasty.

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.