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Biomedical subjects

R H Clarke

Publications and source records attributed to R H Clarke.

At least 55 records · Page 3Linked to original sources

Laser photoablation of pathological endocardium: in vitro findings suggesting a new approach to the surgical treatment of refractory arrhythmias and restrictive cardiomyopathy.

In selected patients, malignant ventricular tachyarrhythmias have been successfully abolished by excision of subendocardial arrhythmogenic foci. Likewise, in certain patients in whom restrictive cardiomyopathy is due to endocardial thickening, endocardial resection has resulted in hemodynamic improvement. The present study was designed to explore the utility, in vitro, of laser photoablation of pathologically thickened endocardium. Endocardial photoablation was easily accomplished regardless of etiological or anatomical variations using either the focused beam of a carbon dioxide laser or argon laser light delivered through a 200-microns optical fiber. Photoablation of areas as large as 3.9 X 1.3 cm was performed within 40 seconds. The extent or depth of endocardial photoablation could be limited to 2 mm2 in area or 1 mm in depth using either form of laser therapy. These in vitro results suggest that either carbon dioxide or argon laser phototherapy can be successfully applied to the surgical treatment of refractory arrhythmias and restrictive cardiomyopathy. Advantages of laser photoablation include speed and precision. Furthermore, laser photoablation obviates the difficulty associated with conventional techniques in establishing tissue planes.

Argon↗

The excimer laser: gross, light microscopic and ultrastructural analysis of potential advantages for use in laser therapy of cardiovascular disease.

Excimer lasers are pulsed gas lasers that use a mixture of a rare gas and halogen as the active medium to generate pulses of short wavelength, high energy ultraviolet light. A krypton-fluoride gas mixture was used to achieve an excimer emission at a wavelength of 248 nm. A total of 30 atherosclerotic coronary artery segments were irradiated over a range of pulse energies (250 to 750 mJ), repetition rates (2 to 25 Hz), average powers (1.9 to 18.8 watts) and cumulative exposures (3 to 12 seconds). In no case was there gross, light microscopic or ultrastructural evidence of the pathologic injury typically associated with continuous wave laser irradiation of coronary artery segments. Similar results were achieved after excimer laser irradiation of 30 samples of myocardium. Excimer irradiation of calcified aortic valve leaflets accomplished focal debridement without pathologic tissue injury; when total debridement was attempted, however, gross charring was observed. The paucity of pathologic alterations observed after excimer irradiation of cardiovascular tissue may prove beneficial in precisely controlling laser ablation of pathologic tissue without injury to the surrounding normal tissue. Clinical application of excimer laser irradiation requires resolution of several issues, including the development of suitable fiber optics and laser coupling, evaluation of potential ultraviolet toxicity, and demonstration that ultraviolet light can be transmitted through a blood-filled system.

Coronary Disease↗

Factors contributing to perforations resulting from laser coronary angioplasty: observations in an intact human postmortem preparation of intraoperative laser coronary angioplasty.

This investigation was designed to assess the potential use of laser coronary angioplasty as an intraoperative adjunct in the surgical treatment of ischemic heart disease. Among 17 postmortem hearts, simulated laser coronary angioplasty was performed at 53 sites with a No. 4F guiding catheter and 240 micron (200 micron core) quartz optical fiber. Perforation complicated laser coronary angioplasty in 33 (62%) of the 53 attempts. Most (n = 29) perforations were thermal; four were purely mechanical. Perforation sites were characterized by extensive calcific deposits (21 of 33 cases [64%] ) and the origin of a side branch (13 of 33 [39%] ). Excessive tortuosity of the extramural coronary artery contributed to arterial perforation in four cases, and precluded attempts to perform laser coronary angioplasty in two other cases. In 19 of the 53 attempts to perform laser coronary angioplasty, a high-frequency two-dimensional echocardiographic probe was used to image the coronary artery during antegrade manipulation of the optical fiber/guiding catheter and laser irradiation of the target arterial stenosis. Although perforation nevertheless occurred in 11 (58%) of 19 sites, only one mechanical perforation resulted; the remaining 10 were thermal. Characteristics of the perforation sites in this group were similar to those noted for the group as a whole. Experience with this model of laser coronary angioplasty indicates that even when access problems associated with percutaneous laser coronary angioplasty are obviated by a simulated intraoperative approach, perforation of the underlying coronary arterial wall continues to represent the "rate-limiting" complication of laser coronary angioplasty. Most perforations occurred in relation to calcific deposits, branch points, and tortuous coronary segments.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Laser myoplasty for hypertrophic cardiomyopathy. In vitro experience in human postmortem hearts and in vivo experience in a canine model (transarterial) and human patient (intraoperative).

The feasibility of performing a myotomy/myectomy for hypertrophic cardiomyopathy (HC) by means of laser phototherapy was evaluated experimentally in vitro and in vivo, and the procedure then applied to a patient intraoperatively. In vitro experience revealed that the beam of an argon laser, delivered directly or via an optical fiber, could both cut and vaporize myocardium, producing a myotomy/myectomy morphologically similar to that produced by the conventional blade technique. In vivo experiments, in which the beam of an argon laser was delivered via an optical fiber to the ventricular septum of a canine heart, confirmed that a laser myoplasty could be achieved in 4 of 5 dogs by a transarterial approach. Finally, laser myoplasty was performed intraoperatively in a patient with HC, using a 200-mu fiber interfaced with an argon laser. Measured laser power was 1.5 W; cumulative exposure was less than 4 minutes; the myoplasty was 4 X 1 X 0.5 cm. These investigations establish the feasibility of using laser therapy to create a myoplasty trough that is similar in appearance to that typically achieved by the conventional blade technique. Illumination of the intraventricular operative field and precise modeling of the myoplasty trough constitute the principal advantages of laser myoplasty for HC.

Adult↗

Transcatheter fiberoptic laser coagulation of blood vessels.

In ten rabbit ears the central auricular artery was percutaneously catheterized and subjected to doses of laser energy transmitted through a flexible optical fiber within the artery. Arterial occlusion was not produced in the initial three ears using energy levels less than 600 mW. Higher levels of laser energy, in the range of 800-1000 mW, caused arterial coagulation in six of the remaining seven rabbit ears. Serial observations by transillumination of the ears, postmortem angiography, and histologic examination demonstrated complete arterial ablation. The experiments showed that segmental arterial ablation is feasible using an intra-arterial optical fiber to direct laser energy to a specific arterial target. Technical refinements and potential therapeutic application are discussed.

Animals↗

Quantitative assessment of carcinogenic risks associated with 'hot particles'.

We have examined the hot particle problem in terms of the number of irradiated cells and the doses to which they are subjected, assuming both linear and nonlinear dose-response functions typical of those reported in the radiobiological literature. We assess the risk associated with point sources of alpha, beta and gamma activity compared with uniform irradiation, as well as the effects of fractionation of a single particle, and the change in risk if the particle moves. Finally, although the biological data are insufficient for firm estimates, we have tentatively attributed absolute carcinogenic risks in these various situations.

Cells↗

Carcinogenesis and radiation risk: a biomathematical reconnaissance.

The biological effects of radiation are often correlated with the dose of radiation received by the tissue or cells at risk, though other physical factors such as spatial or temporal dose distributions, total number of cells irradiated, or relative biological effectiveness are also relevant. In attempting an estimate of biological effect, for example carcinogenesis, it is frequently assumed that the risk is simply proportional to the dose received, though biological experiment often reveals a much more complex relation between effect and dose. We have therefore examined in some detail certain of the consequences of taking into account such a complex relationship in assessing "risk" on the basis of "dose". We first examine the effect of size of population of cells at risk. If tumours arise from chance interactions of cells and ionizing particles we might imagine that large animals containing many orders of magnitude more cells might be much more at risk. A survey of literature shows no evidence that this is so, and of course mere mass might be expected to be a poor parameter for defining carcinogenic risk. As between tissues, DNA content combined with metabolic parameters or "proliferative potential" would be better. However, the literature does show that for a single co-ordinated tissue or organ the fraction of that tissue irradiated is significant. There is clearly some correlation with number of cells at risk. We therefore proposed a formula relating the risk of a cell population to a rare event, such as the "transformation" of a cell or group of cells to an overt tumour. We assume a spatial pattern of dose administered to a defined group of cells reacting according to an assumed dose-response relationship. The assumptions are, biologically speaking, very crude, and we discuss some of the ensuing limitations. The formula may, however, be used to attack a number of important problems. First it is necessary to discuss the forms of dose-response relationships derived theoretically and also observed in radiobiology. Several are chosen for detailed study, particularly responses rising more rapidly than dose at low levels, then reaching a maximum and declining with increasing dose. It is pointed out that there are many possible explanations of this decline at high dose, ranging form cell "death" to "sterilization" or to mutual interaction of neighbouring cells. It can also arise from simple statistical consideration of the probability of multiple events necessary for carcinogenesis in the same or neighbouring cells.

Age Factors↗