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Biomedical subjects

L I Deckelbaum

Publications and source records attributed to L I Deckelbaum.

At least 37 records · Page 2Linked to original sources

Effect of injectate temperature and thermistor position on reproducibility of thermodilution cardiac output determinations.

STUDY OBJECTIVE: The purpose of this study was to evaluate the effect of thermistor position with varying injectate temperatures on the reproducibility of thermodilution cardiac output determination. The key hypothesis to be tested was that the positioning of the proximal thermistor at the right atrial port would improve the reproducibility of thermodilution cardiac output determination, independent of injectate temperature. DESIGN: Prospective randomized trial. SETTING: The study was performed in the cardiac catheterization laboratory of the West Haven Veterans Affairs Medical Center. PARTICIPANTS: Twenty consecutive patients undergoing right and left heart catheterizations were enrolled in the study. INTERVENTIONS: Each patient underwent triplicate determination of thermodilution cardiac output measurements under four experimental conditions: (1) ambient or room temperature injectate using an external thermistor in the injectate reservoir; (2) iced injectate using an external thermistor; (3) room temperature injectate using an internal right atrium (RA) thermistor; and (4) iced injectate using an RA thermistor. Reproducibility was assessed by the coefficient of variation (CV) and standard error of the mean percent (SEM%), of the triplicate measurements. MEASUREMENTS AND RESULTS: Using an internal RA thermistor improved the reproducibility of cardiac output determinations independent of injectate temperature. Using room temperature injectate, the CV was 12.8 percent using an external thermistor and 7.9 percent using an internal RA thermistor (p < 0.05). Using iced injectate, the CV was 10.2 percent using an external thermistor and 5.5 percent using an internal RA thermistor (p < 0.05). CONCLUSIONS: Reproducibility of thermodilution cardiac output determinations is improved when injectate temperature is measured internally, at the RA, as opposed to externally in the reservoir. This has clinical implications for determining significant changes in serial cardiac output determinations.

Analysis of Variance↗

Photoinhibition of smooth muscle cell migration: potential therapy for restenosis.

Evidence from animal, autopsy, and atherectomy studies demonstrates that migration and proliferation of smooth muscle cells of medial origin result in neointima formation and decreased luminal cross-sectional area. The purpose of this study was to evaluate whether low energy light irradiation can inhibit smooth muscle cell migration and therefore potentially reduce the degree of neointima formation and the incidence of restenosis. The migration kinetics of bovine aortic smooth muscle cell monolayers were examined using a fence assay. The effect on smooth muscle cell migration of irradiation with monochromatic light at wave-lengths ranging from 400 to 700 nm was compared to the migration of cells irradiated with broadband white light or maintained in the dark. Wavelength specific photoinhibition of smooth muscle cell migration was observed; 594-600 nm light reproducibly inhibited migration by 12-29% (P < 0.05). Migration rate was significantly reduced following daily radiant exposures of 1.0 J/cm2 as well as following a single radiant exposure of 0.09 or 0.9 J/cm2. The decrease in migration was not associated with any change in cell proliferation or [3H] thymidine incorporation. We conclude that 594-600 nm light inhibits smooth muscle cell migration in vitro and may potentially be used in vivo to decrease fibrointimal thickening following arterial injury. This application of photoinhibition may be useful in retarding restenosis following angioplasty.

Animals↗

Control of smooth muscle cell proliferation by psoralen photochemotherapy.

PURPOSE: Restenosis after balloon angioplasty or the intimal hyperplasia occurring at distal anastomoses of bypass grafts severely limits the long-term therapy for peripheral vascular disease. The aim of this study was to evaluate the application of psoralen photochemotherapy with ultraviolet A (UVA)-activated 8-methoxypsoralen (8-MOP) to suppress smooth muscle cell (SMC) proliferation in vitro by the formation of 8-MOP-DNA monoadducts and interstrand cross-links to inhibit DNA synthesis. METHODS: Bovine aorta SMC (2 x 10(4)/cm2) were treated with 8-MOP (0 to 1000 ng/ml) for 30 minutes, followed by UVA (2 joule/cm2) to determine the dose of 8-MOP and UVA that inhibits SMC proliferation. RESULTS: The results show that 8-MOP in the range 30 to 1000 ng/ml in combination with 2 joule/cm2 UVA inhibited SMC proliferation by 40% to 60% 3 days after treatment. In time course studies the growth of SMC treated with 100 ng/ml 8-MOP and 2 joule/cm2 UVA were monitored over 5 days, and this regimen was found to be cytostatic. SMC viability was confirmed by trypan blue exclusion. CONCLUSIONS: Our studies suggest that 8-MOP/UVA photochemotherapy may represent a novel approach to the control of localized SMC proliferation.

Animals↗

The excitation of 8-methoxypsoralen with visible light: reversed phase HPLC quantitation of monoadducts and cross-links.

The formation of 8-methoxypsoralen-DNA monoadducts and cross-links is presumed to be responsible for the efficacy of photochemotherapies that employ 8-methoxypsoralen activated with long-wavelength ultraviolet radiation (UVA, 320-400 nm). In this report it is shown that 8-methoxypsoralen can also be activated with visible light (419 nm). Bovine aorta smooth muscle cells were treated with 8-methoxypsoralen (1,000 ng/mL) and 419 nm light (up to 12 J/cm2). Cellular DNA was isolated, hydrolyzed using nucleolytic enzymes and then analyzed by reversed-phase high-performance liquid chromatography. The primary effect of using visible light instead of long-wavelength ultraviolet radiation is a more than 10-fold reduction in the extent of cross-link formation. Because the extent of monoadduct and cross-link formation has not been routinely measured in experiments in which cellular assays have been performed, it is difficult to correlate cell response to the presence of a particular type of 8-methoxypsoralen photoadduct (monoadduct or cross-link). Thus, the use of visible light allows the study of cells containing nearly 100% monoadducts. In addition, the reduction in cross-link formation when visible light is used to activate the compound may also reduce the mutagenicity of 8-methoxypsoralen and hence enhance its therapeutic efficacy.

Animals↗

Detection of calcified atherosclerotic plaque by laser-induced plasma emission.

The use of fluorescence spectroscopy to discriminate atherosclerotic from normal tissue is limited by a lower sensitivity for calcified than noncalcified atherosclerotic plaque (65% vs. 93%, respectively). To evaluate plasma emission as a means to detect calcified plaque, 325 normal and atherosclerotic cadaveric aortic sites were irradiated through a 100-micron silica fiber in blood by a pulsed holmium laser (lambda = 2.1 microns, fluence = 4 J/mm2). A photodiode positioned near the proximal end of the fiber detected plasma emission during a laser pulse. Plasma emission was detected at 0% (0/110) of normal, 0% (0/107) of noncalcified atherosclerotic tissue, and 91% (98/108) of calcified atherosclerotic sites. Spectroscopic analysis confirmed the presence of calcium lines in the plasma emission from calcified atherosclerotic plaque. Although ablative fluences (greater than 3 J/mm2) were required for plasma generation, a single laser pulse ablated only to a depth of 67 +/- 16 microns in normal tissue. In an additional 10 calcified atherosclerotic sites, laser ablation was continued as long as plasma emission was detected. In all cases, plaque ablation was terminated before arterial perforation. Furthermore, the adjunctive use of plasma detection improved the accuracy of fluorescence spectroscopic classification of normal and atherosclerotic tissue. In conclusion, plasma detection has a high sensitivity (91%) and specificity (100%) for calcified atherosclerotic plaque and may be a useful adjunct for laser angioplasty guidance. Furthermore, plasma detection can be implemented both simply and inexpensively.

Aluminum Silicates↗

Validation of continuous radionuclide left ventricular functioning monitoring in detecting silent myocardial ischemia during balloon angioplasty of the left anterior descending coronary artery.

Silent myocardial ischemia has been inferred from transient ST-segment depression during continuous electrocardiographic monitoring. Recently, continuous ambulatory monitoring of left ventricular (LV) function using a radionuclide technique (VEST) has demonstrated episodes of significant silent LV dysfunction in the absence of electrocardiographic changes. To validate the demonstration of silent LV dysfunction with this technique, 12 men were studied during percutaneous transluminal coronary angioplasty. A total of 18 left anterior descending coronary artery balloon inflations were performed. Balloon inflations at 8 +/- 2 atm (4 to 10 atm) lasted 70 +/- 16 seconds. Seventeen of 18 inflations were associated with a decrease in LV ejection fraction greater than 0.10. Mean LV ejection fraction decreased from 0.53 +/- 0.08 to 0.28 +/- 0.11 (p less than 0.0001). In contrast, there was pain in only 10 inflations and ST-segment changes in 7. LV dysfunction was associated with a minimal increase in end-diastolic volume (4 +/- 3%, p less than 0.003), and a major increase in relative end-systolic volume (69 +/- 43%, p less than 0.001). These data suggest that continuous monitoring of LV function with the VEST can sensitively detect silent ischemic decreases in LV function occurring during angioplasty, and provide further validation of the use of this technique for detecting silent myocardial ischemia.

Aged↗

Design and evaluation of a fiberoptic fluorescence guided laser recanalization system.

Current angioplasty techniques for recanalization of totally occluded arteries are limited by the inability to cross the occlusion and by the risk of perforation. A fiberoptic fluorescence guided laser recanalization system was developed and evaluated in vitro for recanalization of 17 human femoral or tibial totally occluded arterial segments (length 1.9-6.8 cm, diameter 2.5-6.0 mm). A 400 or 600 micron silica fiber was coupled to a helium-cadmium laser (lambda = 325 nm) for fluorescence excitation and to a holmium: YAG laser (lambda = 2.1 micron) for tissue ablation. Fluorescence was recorded during recanalization after every other holmium laser pulse. During recanalization, each arterial segment was bent 30-90 degrees with respect to the fiber to simulate arterial tortuosity. Ablation continued with fiber advancement as long as the fluorescence confirmed that the target tissue was atherosclerotic. Arterial spectra were classified as normal or atherosclerotic by an on-line computerized fluorescence classification algorithm (sensitivity 93%, specificity 95%). Normal fluorescence necessitated redirection of the fiber greater than 30 times per segment to continue recanalization. Fifteen of 17 totally occluded arteries had multiple recanalization channels created following total energy delivery of 40-1,016 Joules per segment with no angiographic or histologic evidence of laser perforation. Two heavily calcified arterial occlusions were not recanalized due to inhibition of holmium: YAG laser ablation by the recording of normal fluorescence spectra. Therefore, this fluorescence guided laser recanalization system appears safe and effective for recanalization of totally occluded arteries and merits in vivo evaluation. However, the lower sensitivity of fluorescence detection of heavily calcified plaques may limit the efficacy (but not safety) of fluorescence guided recanalization of heavily calcified occlusions.

Angioplasty, Laser↗

Neural network and conventional classifiers for fluorescence-guided laser angioplasty.

In laser angioplasty, fluorescence spectra of targeted tissue may be used to classify the tissue as atherosclerotic or normal and guide selective laser ablation of atherosclerotic plaque. Here, the ability of the back-propagation and K-nearest neighbors techniques to classify arterial fluorescence spectra is investigated. Both methods are competitive with other classification schemes. The relative performance of variations on both techniques is used to make inferences about the geometry of the classification task.

Angioplasty, Laser↗

Myocardial protein turnover in patients with coronary artery disease. Effect of branched chain amino acid infusion.

The regulation of protein metabolism in the human heart has not previously been studied. In 10 postabsorptive patients with coronary artery disease, heart protein synthesis and degradation were estimated simultaneously from the extraction of intravenously infused L-[ring-2,6-3H]phenylalanine (PHE) and the dilution of its specific activity across the heart at isotopic steady state. We subsequently examined the effect of branched chain amino acid (BCAA) infusion on heart protein turnover and on the myocardial balance of amino acids and branched chain ketoacids (BCKA) in these patients. In the postabsorptive state, there was a net release of phenylalanine (arterial-cardiac venous [PHE] = -1.71 +/- 0.32 nmol/ml, P less than 0.001; balance = -116 +/- 21 nmol PHE/min, P less than 0.001), reflecting protein degradation (142 +/- 40 nmol PHE/min) in excess of synthesis (24 +/- 42 nmol PHE/min) and net myocardial protein catabolism. During BCAA infusion, protein synthesis increased to equal the degradation rate (106 +/- 24 and 106 +/- 28 nmol PHE/min, respectively) and the phenylalanine balance shifted (P = 0.01) from negative to neutral (arterial-cardiac venous [PHE] = 0.07 +/- 0.36 nmol/ml; balance = 2 +/- 25 nmol PHE/min). BCAA infusion stimulated the myocardial uptake of both BCAA (P less than 0.005) and their ketoacid conjugates (P less than 0.001) in proportion to their circulating concentrations. Net uptake of the BCAA greatly exceeded that of other essential amino acids suggesting a role for BCAA and BCKA as metabolic fuels. Plasma insulin levels, cardiac double product, coronary blood flow, and myocardial oxygen consumption were unchanged. These results demonstrate that the myocardium of postabsorptive humans is in negative protein balance and indicate a primary anabolic effect of BCAA on the human heart.

Aged↗

Characterization of the site dependency of normal canine arterial fluorescence.

The difference in fluorescence between normal and atherosclerotic artery has been proposed as a feedback mechanism to guide selective laser ablation of atherosclerotic plaque. This fluorescence difference is due to the relative difference in collagen:elastin content of normal artery and atherosclerotic plaque. However, normal arteries have site-dependent variation in collagen: elastin content which may affect their fluorescence spectra. To evaluate the site dependency of normal arterial fluorescence, helium-cadmium (325 nm) laser-induced fluorescence spectra were analyzed in vitro from the ascending aorta, abdominal aorta, and carotid, femoral, renal, and coronary arteries (N = 57) of 12 normal mongrel dogs. Elastin and collagen contents were determined for a subset of these arteries (N = 15). The spectral width of normal arterial Fluorescence varied by site and correlated with the measured collagen:elastin content at each site (r = -0.84, P less than 0.005). Fluorescence spectra were decomposed into collagen and elastin spectral components by using a linear model with a least-squared error criterion fit. The derived collagen and elastin spectral coefficients correlated with the measured collagen and elastin tissue content (r = 0.75 and 0.83 respectively, P less than 0.005). Thus, the fluorescence spectra of normal arteries is site dependent and correlates with the collagen:elastin content. Therefore, spectral feedback algorithms for laser angioplasty guidance must be site specific.

Animals↗

Laser-induced fluorescence spectroscopy of human colonic mucosa. Detection of adenomatous transformation.

To evaluate the potential of laser-induced fluorescence spectroscopy for the detection of premalignant lesions of the gastrointestinal tract, the hypothesis that adenomatous transformation of colonic mucosa results in an alteration of laser-induced fluorescence that enables its differentiation from normal or hyperplastic tissue was tested. A fiberoptic catheter coupled to a helium-cadmium laser (325 nm) and an optical multichannel analyzer were used to obtain fluorescence spectra (350-600 nm) from 35 normal colonic specimens and 35 resected adenomatous polyps. A score based on six wavelengths was derived by stepwise multivariate linear regression analysis of the spectra. The mean score (+/- SEM) was + 0.86 +/- 0.06 for normal mucosa and -0.86 +/- 0.06 for adenomatous polyps (P less than 0.001). Spectra from an additional 34 normal specimens, 16 adenomatous polyps, and 16 hyperplastic polyps were prospectively classified with accuracies of 100%, 100%, and 94%, respectively. The mean score for hyperplastic polyps was significantly different from adenomatous (P less than 0.001) but not from normal tissue. Thus, quantitative analysis of fluorescence spectra enables the detection of adenomatous transformation in colonic mucosa.

Adenomatous Polyposis Coli↗

Change in laser-induced arterial fluorescence during ablation of atherosclerotic plague.

Analysis of the change in arterial fluorescence during plaque ablation may provide the basis for developing a fluorescence-guided ablation system capable of selective plaque ablation without risk of vessel perforation. Accordingly, fluorescence spectra were recorded from 91 normal and 91 atherosclerotic specimens of cadaveric human aorta. The ratio of the laser-induced fluorescence intensity at 382 nm to 430 nm (LIF ratio) was capable of classifying these specimens with an 89% accuracy with a threshold value of 1.8 (atherosclerotic greater than or equal to 1.8, normal less than 1.8). To characterize the change in fluorescence during plaque ablation, mechanical plaque ablation with a cold microtome was performed on 16 atherosclerotic aortic specimens. Fluorescence spectra were recorded serially after each 100 microns of plaque ablation; recordings revealed a change in fluorescence spectra from atherosclerotic to a normal pattern. With an LIF ratio of 1.8 to signal termination of plaque ablation, 15 of the atherosclerotic plaques had a residual plaque thickness less than 200 microns; one specimen had a residual plaque thickness of 300 microns. No specimen demonstrated ablation of the media. There was a statistically significant correlation between LIF ratio and plaque thickness (r = .73, P less than .001), but considerable variation in LIF ratio existed at each thickness. Therefore, laser-induced fluorescence spectroscopy is capable of discriminating atherosclerotic from normal aorta and of signaling completion of plaque ablation.

Angioplasty, Balloon↗

Fluorescence spectroscopy guidance of laser ablation of atherosclerotic plague.

Laser-induced fluorescence (LIF) spectroscopy can only be used for laser angioplasty guidance if high-power laser ablation does not significantly alter the pattern of tissue fluorescence. Although the spectra of normal and atherosclerotic arteries differ, the change in fluorescence spectra following laser angioplasty has not been well studied. Therefore, the purpose of this study was to assess whether laser-induced fluorescence spectroscopy could guide selective laser ablation of atherosclerotic plaque and, if so, to develop a quantitative LIF score that could be used to control a "smart" laser angioplasty system. Baseline LIF spectroscopy of 50 normal and 50 atherosclerotic human aortic specimens was performed using an optical fiber coupled to a He-Cd laser and optical multichannel analyzer. LIF was then serially recorded during erbium:YAG laser ablation of 27 atherosclerotic specimens. Laser ablation was terminated when the arterial LIF spectrum visually appeared normal. Histologic analysis revealed a mean initial plaque thickness of 1,228 +/- 54 microns and mean residual plaque thickness of 198 +/- 27 microns. Ablation of the media occurred in only three specimens. A discriminant function was derived to discriminate atherosclerotic from normal tissue for computer guidance of laser angioplasty. The LIF score, derived from stepwise multivariate linear regression analysis of the LIF spectra, correctly classified 93% of aortic specimens. The spectra obtained from the atherosclerotic specimens subjected to fluorescence-guided laser revealed a change in score from "atherosclerotic" to "normal" following plaque ablation. Seven atherosclerotic specimens were subjected to laser angioplasty with on-line computer control using the LIF score. Mean initial plaque thickness was 1,014 +/- 86 microns, and mean residual plaque thickness was 78 +/- 29 microns. There was no evidence of ablation of the media. Therefore, LIF guidance of laser ablation resulted in minimal residual plaque without arterial perforation. These findings support the feasibility of an LIF-guided laser angioplasty system for selective atherosclerotic plaque ablation.

Arteriosclerosis↗

Development and evaluation of spectral classification algorithms for fluorescence guided laser angioplasty.

Laser angioplasty, or the ablation of atherosclerotic plaque using laser energy, has tremendous potential to expand the scope of nonsurgical treatment of obstructive vascular disease. Clinical laser angioplasty, however, has been hindered by an unacceptable risk of vessel perforation. Laser-induced fluorescence spectroscopy can discriminate atherosclerotic from normal artery and may therefore be capable of guiding selective plaque ablation. To assess the feasibility of utilizing spectral information to discriminate arterial tissue type, several classification algorithms were developed and evaluated. Arterial fluorescence spectra from 350 to 700 nm were obtained from 100 human aortic specimens. Seven spectral classification algorithms were developed with the following techniques: multivariate linear regression, stepwise multivariate linear regression, principal components analysis, decision plane analysis, Bayes decision theory, principal peak ratio, and spectral width. The classification ability of each algorithm was evaluated by its application to the training set and to a validation set containing 82 additional spectra. All seven spectral classification algorithms prospectively classified atherosclerotic and normal aorta with an accuracy greater than 80 percent (range: 82-96 percent). Laser angioplasty systems incorporating spectral classification algorithms may therefore be capable of detection and selective ablation of atherosclerotic plaque.

Algorithms↗

Biochemical basis for the difference between normal and atherosclerotic arterial fluorescence.

The observation that laser-induced fluorescence (LIF) spectra of atherosclerotic and normal artery are different has been proposed as the basis for guiding a "smart" laser angioplasty system. The purpose of this study was to investigate the causes of this difference in LIF. Helium-cadmium laser-induced (325 nm) fluorescence was recorded from pure samples of known constituents of normal and atherosclerotic artery including collagen, elastin, calcium, cholesterol, and glycosaminoglycans. Similarities between the LIF spectra of atherosclerotic plaque and collagen and normal aorta and elastin were noted. LIF spectroscopy was then performed on specimens of atherosclerotic aortic plaque (n = 9) and normal aorta (n = 13) and on their extracted lipid, collagen, and elastin. Lipid extraction did not significantly alter atherosclerotic plaque or normal aortic LIF, suggesting a minor contribution of lipid to arterial LIF. The LIF spectra of normal aorta wall was similar to the spectra of the extracted elastin, whereas the LIF spectra of atherosclerotic aortic plaque was similar to the spectra of the extracted collagen. These observations are consistent with the reported relative collagen-to-elastin content ratio of 0.5 for normal arterial wall and 7.3 for atherosclerotic plaque. A classification algorithm was developed to discriminate normal and atherosclerotic aortic spectra based on an elastin and collagen spectral decomposition. A discriminant score was formed by the difference of elastin and collagen (E-C) coefficients and used to classify 182 aortic fluorescence spectra. The mean E-C value was +0.83 +/- 0.04 for normal and -0.48 +/- 0.07 for atherosclerotic aorta (p less than 0.001). Classification accuracy was 92%.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms↗

System design considerations for laser angioplasty.

Laser angioplasty, or the use of laser radiation to vaporize or remove obstructure atherosclerotic plaque, has been an active area of research for the past several years. This article reviews current design considerations for developing a safe, effective clinical laser angioplasty system. The choice of laser, fiber, and catheter determines the performance characteristics of such a system. The laser provides the power source for ablative radiation, the fiber furnishes a means of transmitting the laser radiation, and the catheter provides a way of directing the fiber at the target tissue. Other considerations, such as the need for feedback control of laser ablation and the planned application of the system in the coronary or peripheral circulation, also determine the ultimate design.

Journal Article↗