Biomedical subjects
Publications and source records attributed to R H Clarke.
We present results of a series of laser spectroscopic measurements on in vitro samples of cardiovascular tissue. These include laser Raman scattering, Fourier transform infrared, plasma emission and fluorescence, and electron paramagnetic resonance spectroscopy. The results of these spectroscopic measurements are discussed in terms of their implications for the field of laser angioplasty.
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.
Selection of a laser source for intravascular applications has frequently been predicated upon assumptions involving transmissibility in blood of the wavelength of light emitted by a given laser. Standard absorption curves for ultraviolet radiation in blood and infrared radiation in water would suggest that transmission of ultraviolet radiation through a blood field and infrared radiation through any aqueous fluid field would be insufficient for tissue ablation. The present series of experiments was undertaken to determine whether these theoretical predictions would in fact obviate the use of these wavelengths in a blood field. Specimens of normal human myocardium and/or polyvinylchloride were submerged under blood and water and irradiated with ultraviolet radiation (351 nm) delivered as a focused beam and via an optical fiber and infrared radiation (10,600 nm) delivered as a focused beam. Ablation of myocardium was successfully accomplished with a focused beam of both ultraviolet and infrared radiation under as much as 5 mm of blood and with ultraviolet radiation via an optical fiber with the fiber tip up to 3 mm distant from the tissue specimen. High-speed cine recordings of ablation carried out using a focused beam of laser radiation demonstrated that formation of a dynamic optical cavity is the basis for successful pulsed ultraviolet and infrared laser transanguineous tissue ablation. These results thus demonstrate that prediction of wavelength transmission through fluid media based on optical properties of a static fluid does not predict ability to accomplish ablation under dynamic circumstances of laser irradiation.
Laser energy was fiberoptically transmitted into the carotid artery of a series of rabbits to induce an acute focal arterial occlusion. Temporary interruption of blood flow during the treatment was necessary to achieve an occlusion. The arterial occlusive effects of three wavebands of laser energy were compared and the violet band proved the most effective when using 0.3-0.5 Joules/second for 25-30 seconds. There was always the risk of vascular perforation during treatment when laser energy emission was from a bare-tipped optical fiber.
Using the method of spin trapping and electron paramagnetic resonance, free radicals have been detected accompanying laser ablation of cardiovascular tissue. Radicals were detected using both visible and ultraviolet laser energy from argon-ion and excimer laser sources. The results are discussed in terms of the relative efficiency of the laser wavelengths to produce free radicals and a comparison of the types of radicals produced by the action of pulsed versus cw laser energy.
To study the effect of argon laser irradiation on vascular smooth muscle reactivity, ring segments of rabbit thoracic aorta were mounted isometrically in Krebs bicarbonate buffer. Laser irradiation was performed via a 200-micron core optical fibre interfaced with an argon ion gas laser. Laser irradiation at powers greater than 1.0 watt (W) (n = 34) produced contraction in each case, regardless of the duration of exposure. Conversely, irradiation at powers less than 0.1 W (n = 41) consistently produced relaxation. When the power employed ranged from 0.1 to 1.0 W (n = 100), the typical response consisted of a combination of low amplitude contraction and relaxation. At each power level, the responses observed were independent of the presence or absence of intact endothelium, assessed functionally by the response to acetylcholine and anatomically by scanning electron microscopy. Recordings of tissue temperature profiles performed during continuous-wave laser irradiation suggest that the findings observed in this study may be explained by a combination of heat induced contraction and light induced relaxation. At powers greater than 1.0 W, heat generated by laser irradiation is predominant, causing contraction. At powers less than 0.1 W, light predominates over heat, causing relaxation. When the power range is intermediate between these values, the heterogeneous response recorded reflects the combination of light and heat. In all cases, contraction and relaxation are endothelium independent.
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Previous in vitro investigations utilizing necropsy specimens have suggested a potential role for laser irradiation in the treatment of refractory ventricular tachyarrhythmias associated with pathologically thickened endocardium. In the patient described in the present report, findings of these previous in vitro studies were applied intraoperatively to a patient undergoing surgery for ischemic heart disease associated with ventricular tachyarrhythmias. Aneurysm resection and manual subendocardial resection were performed using standard techniques. Laser irradiation was used to ablate pathologically thickened endocardium involving the papillary muscle and thereby avoid mitral valve replacement. Postoperatively, there was no auscultatory evidence of mitral regurgitation, and ventricular tachycardia could not be induced by electrophysiologic provocative testing. This preliminary experience confirms that laser irradiation is both a feasible and potentially advantageous means of accomplishing endocardial debridement in patients undergoing arrhythmia-ablation procedures.
The present series of experiments used gas chromatography to identify vapor-phase photoproducts liberated during excimer laser irradiation of cardiovascular tissues in air and blood. In air, laser beams produced from ArF (193 nm) and XeF (351 nm) excimer laser gas mixtures were delivered to samples of myocardium and atherosclerotic coronary arterial segments through the wall of a quartz cell, using 8-40 mJ/pulse. In blood, 351 nm were delivered via an optical fiber, using 14 mJ/pulse. When the experiments were performed using an air-tissue interface, the dominant photoproducts identified in order of elution from the gas chromatographic column were methane, acetylene, ethylene, ethane, propyne, allene, propylene, propane, and butene. When a fiberoptic was used to accomplish 351-nm excimer laser tissue ablation in a blood field, a similar gas chromatographic spectral distribution was observed. These vapor-phase photoproducts are indistinguishable from those observed following continuous wave laser irradiation or flame torching of cardiovascular tissues. Thus, despite the fact that excimer laser ablation of cardiovascular tissues is characterized by the absence of signs of thermal injury, the results of these experiments suggest that the predominant mechanism of excimer ablation is, like continuous-wave laser irradiation, a thermal process.
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Human coronary artery wall architecture was analyzed in detail in 127 histologic sections with varying degrees of narrowing due to atherosclerotic plaque. A planimetry-microscope system was used to morphometrically determine percent luminal cross-sectional area narrowing due to atherosclerotic plaque, absolute area of the coronary artery media and total cross-sectional area of the coronary artery section. In 65 sections in which the native coronary artery lumen was narrowed less than 75%, the area of the coronary artery media corrected for total coronary cross-sectional area (Mc) was 0.244 +/- 0.055 mm2. In contrast, among 62 sections in which the coronary artery lumen was narrowed more than 75% in cross-sectional area, Mc measured 0.180 +/- 0.078 (p less than 0.001). Thus, in coronary artery segments with advanced atherosclerosis, there is substantial attenuation of the media, normally the principal component of the coronary artery wall.
The carbon dioxide (CO2) laser has been utilized for preliminary intraoperative cardiovascular applications, including coronary endarterectomy and ventricular endocardiectomy. CO2 lasers used for these applications have been operated in the continuous wave, chopped or pulsed mode at low peak powers. To evaluate the extent of boundary tissue injury, continuous, chopped and pulsed energy delivery of CO2 laser emission was used to bore through 192 5 mm thick myocardial slices in air. Continuous, chopped and pulsed delivery at a peak power of 500 W or less failed to eliminate light microscopic or ultrastructural signs of thermal injury. Only when a high energy CO2 laser (pulse energy 80 to 300 mJ, pulse duration 1 microseconds) was used at a peak power greater than 80 kW were all signs of thermal injury eliminated; furthermore, high peak power prevented thermal injury only when the beam was focused to achieve a peak power density greater than 60 kW/mm2. Under these conditions, pathologic findings were identical to those observed using excimer wavelengths. The results of these experiments indicate that: conventional CO2 lasers fail to minimize boundary tissue injury, elimination of thermal injury during intraoperative laser ablation requires that CO2 laser energy be focused to achieve a peak power density greater than 60 kW/mm2, and elimination of thermal injury can be achieved at a variety of wavelengths, provided that an appropriate energy profile is employed.
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Rebleeding after aneurysmal subarachnoid hemorrhage has a 45 per cent mortality rate. The peak incidence is within 24 hours of the initial bleed. During the ensuing 2 weeks 20 per cent of patients with suffer a second hemorrhage. To avoid this, surgical treatment must be instituted promptly but, logistically, this is often difficult to implement. To this end, we have devised an intravascular laser-catheter technique that may provide expeditious treatment for intracranial aneurysms. We have coagulated experimental aneurysms in the rabbit carotid artery using laser energy transmitted through an intra-arterial optical fiber. The special fiber tip was positioned in the aneurysm by a catheter introduced from the femoral artery. Laser power of 750 mW and an exposure of 15 seconds caused aneurysm ablation leaving the feeding artery patent. To date, 4 experimental aneurysms have been occluded by this technique and long term histologic results are pending in this ongoing study.
Continuous-wave (CW) laser irradiation of cardiovascular tissues is characterized by 2 distinctive histologic findings: a superficial zone of coagulation necrosis and a subjacent zone of polymorphous lacunae. The present investigation was designed to determine whether such injury could be eliminated by altering the temporal profile of laser energy delivery. One hundred forty-five myocardial slices were irradiated with an air-tissue interface using CW laser irradiation at wavelengths of 488 to 515 nm (argon), 1,064 nm (Nd-YAG) and 10,600 nm (CO2). Pulsed laser irradiation included 248 nm (excimer); 355, 532 and 1,064 nm (Nd-YAG); and 515 nm (mode-locked argon). Energy profiles in the pulsed mode included a range of repetition rates (1 Hz to 256 MHz), pulse duration (0.2 to 358 ns) and pulse energies (2 nJ to 370 mJ). Resultant average powers were 0.1 to 38 W. Grossly visible charring of myocardial tissue was observed at all laser wavelengths when the laser energy profile was CW or pulsed at high repetition rates (more than 2 KHz) and low pulse energies (less than 3 mJ) independent of the wavelengths used. In contrast, when laser energy was pulsed at low repetition rates (less than 200 Hz) and large pulse energies (more than 10 mJ), neither gross nor histologic signs of thermal injury were observed. Pathologic injury associated with laser-induced tissue ablation may thus be substantially reduced by use of pulsed energy delivery at low repetition rates. Potential advantages of pulsed laser energy include a more benign healing process, a less thrombogenic surface, and improved preservation of structural tissue integrity.
To determine how laser light effects alterations in cardiovascular tissue, photoproducts liberated as the result of argon laser irradiation of atherosclerotic plaque, myocardium and calcified aortic valve leaflets were analyzed by gas chromatography, gas chromatography-mass spectrometry and absorbance spectroscopy. The products formed in gas phase are those expected when proteins and porphyrins are pyrolyzed--light hydrocarbon fragments, carbon monoxide and water vapor. The laser-generated products dissolved in solution are those expected when a protein chain or porphyrin ring is degraded in a thermal reaction, namely protein fragments and nitrogen heterocyclic ring fragments. These photoproducts are those typical of combustion or thermal degradation, and indicate that the fundamental nature of laser irradiation of coronary plaque, myocardium and calcified valve leaflets is thermal rather than photochemical. Thermal degradation of myocardium is more extensive than thermal degradation of atherosclerotic arteries or calcified valves because the red hue of myoglobin-containing myocardium enhances the absorption of the blue-green argon laser light. In contrast, the yellow-white hue of both atherosclerotic plaque and calcified aortic valve leaflets allows less complete absorbance of the argon laser light, leading to a lesser amount of converted heat and, therefore, less complete thermal degradation.
Experimental debridement of aortic valve calcium by means of laser phototherapy was investigated in vitro. Near-total debridement of calcific deposits observed on pretreatment x-ray films was accomplished using carbon-dioxide laser phototherapy. Analysis of liberated photoproducts suggests that debridement is effected by thermal degradation of the surrounding connective tissue envelope and thermal expansion of the calcific nodules. These results suggest that in selected patients with calcific aortic stenosis, it may be possible to perform intraoperative laser-assisted debridement of aortic valve calcium in order to preserve the native aortic valve and thus avoid prosthetic valve replacement.