Laser-induced dissections: pathogenesis and implications for therapy.
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Biomedical subjects
Publications and source records attributed to J M Isner.
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Obstruction of the right ventricular outflow tract from metastatic disease is rare. Eleven previous case reports and three new cases are presented. Two tumor types (pancreas and breast), not previously associated with right ventricular outflow tract obstruction, are included. Congestive symptoms, systolic murmur and right axis deviation or right bundle branch conduction abnormality were universal features. Echocardiography is valuable in the delineation of metastatic cardiac involvement and the detection of intracardiac gradients. Adverse hemodynamic consequences developed in 3 of 10 patients who underwent right heart catheterization in which two died. This procedure should be performed only when absolutely necessary. Metastatic obstruction of the right ventricular outflow tract should be considered in the absence of widespread malignancy because the heart was the sole site of metastasis in 5 of 10 autopsy patients. Two patients with solitary cardiac metastasis benefited from resection of the obstructing tumor, underscoring the importance of early identification of this subgroup.
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Laser angioplasty has now been successfully performed on over 2,000 patients worldwide. Two systems (Advanced Interventional Systems, and Spectranetics, Corp.) have now received initial approval from the Food and Drug Administration. As with all new interventional techniques designed as an alternative to balloon angioplasty, there are a variety of instrument related issues that merit consideration in terms of patient selection as well as operator technique. While the ultimate role of laser angioplasty in the percutaneous revascularization of coronary artery disease remains to be established with certainty, laser angioplasty is, in fact, being currently used on a widespread basis as an alternative or an adjunct to balloon angioplasty in a large number of centers worldwide. Industry projections suggest that the use of this technique will increase further over the next decade. Accordingly, the purpose of this article is to discuss specific issues regarding instrumentation, native anatomical considerations, operator technique, and complications that relate specifically to the applied use of this technology as it is currently being used.
To explore the feasibility of computer-based, on-line three-dimensional reconstruction, timed manual withdrawal (pullback) recordings were obtained with two-dimensional intravascular ultrasound (US) in 42 patients who underwent percutaneous revascularization. Three-dimensional processing was performed with commercial software that stacked serially obtained intravascular US scans and created a new set of data points in four steps: interpolation, segmentation, boundary encoding, and surface rendering. In all 42 patients, satisfactory on-line three-dimensional reconstruction was accomplished. In the first three patients, 70-90 seconds was required for three-dimensional processing, and display was limited to the sagittal format. In the next six patients, a sagittal display was rendered in 45-60 seconds, and on-line reconstruction in the cylindrical format was achieved within 30 additional seconds. In the last 33 patients, an unlimited number of sagittal views could be produced in 30-40 seconds, the extra time required for cylindrical display was shortened to 15-20 seconds, and a luminal cast display was added to the on-line menu.
BACKGROUND: The effect of valve deformity and patient age adversely affect the results of percutaneous transvenous mitral commissurotomy (PTMC) with conventional balloons. METHODS AND RESULTS: These factors were characterized after PTMC with the Inoue balloon. The increases in mitral valve area and mitral regurgitation after the procedure were evaluated comparing echocardiographic score of 8 or less versus more than 8, age of less than 60 versus age of 60 years or more, and age of less than 70 versus age of 70 years or more. One hundred sixty-two patients (mean age, 52 +/- 14 years) were studied. For the entire group, mitral valve area increased from 1.0 to 1.8 cm2 (p less than 0.001). Valve area increased from 1.0 +/- 0.3 to 1.8 +/- 0.6 cm2 in patients with echocardiographic score of 8 or less (n = 102) and from 1.0 +/- 0.3 to 1.7 +/- 0.5 cm2 with echocardiographic score of more than 8 (n = 44). Patients less than 60 years old (n = 104) had increases in valve area from 1.0 +/- 0.3 to 1.8 +/- 0.6 cm2 versus 1.0 +/- 0.4 to 1.8 +/- 0.6 cm2 for those 60 years old or older (n = 50) (p = NS). There was no significant difference in resultant valve area when the age division was increased to less than 70 versus 70 years or more. Similarly, the percentage of patients with 2+ or greater increase in mitral regurgitation was not different for those with higher than for those with lower echocardiographic scores (4% versus 12%, p = NS), age of less than 60 versus age of 60 years or more (10% versus 10%, p = NS), or age of less than 70 versus age of 70 or more years (9% versus 18%, p = NS). Valve replacement for mitral regurgitation was performed in four patients (one emergency), all with echocardiographic scores of less than 8. CONCLUSIONS: Age and extent of valve deformity do not have significant effects on acute results of PTMC using the Inoue balloon. Unique balloon geometry or the controlled, stepwise balloon sizing may explain these acceptable acute results in patients with more-deformed valves.
BACKGROUND: Identification of genes that are specifically activated in restenosis lesions after percutaneous transluminal angioplasty represents a necessary step toward molecular manipulation designed to inhibit cellular proliferation responsible for such lesions. Whereas quiescent smooth muscle cells (contractile phenotype) preferentially express smooth muscle myosin, proliferating smooth muscle cells (synthetic phenotype) have been shown to preferentially express nonmuscle myosin in vitro. Accordingly, we analyzed the expression of a recently cloned isoform of human nonmuscle myosin heavy chain (MHC-B) in fresh human restenotic lesions. METHODS AND RESULTS: A total of 10 lesions, including four restenosis (three superficial femoral arterial lesions and one saphenous vein bypass lesion) and six primary (four superficial femoral arterial lesions and two coronary arterial lesions) obtained percutaneously by directional atherectomy, were processed for examination by in situ hybridization. In total, 150 tissue sections of restenotic lesions (66 sections), primary lesions (78 sections), and normal internal mammary artery (six sections) were hybridized with the nonmuscle MHC-B probe. Restenotic lesions showed intense hybridization to the nonmuscle MHC-B cRNA probe, as demonstrated by a clustering of more than 20 grains per cell nucleus in 80% of the cells examined within a high-power field (x250); in contrast, an equivalent degree of hybridization was observed in only 7% of cells within primary lesions (p less than 0.001). Results of immunocytochemistry using monoclonal antibody to smooth muscle actin indicated that cells demonstrating strong hybridization were smooth muscle in origin. CONCLUSIONS: These findings demonstrate that 1) human vascular tissue obtained by percutaneous directional atherectomy constitutes appropriate biopsy material for gene expression studies at the mRNA level, and 2) nonmuscle MHC-B mRNA is present in greater abundance among restenotic versus primary vascular stenoses. These observations thus provide a rational basis to explore restenotic lesions on a larger scale to identify genes that are activated in these lesions and establish potential targets for future gene therapy.
BACKGROUND: Previous in vitro experiments performed in our laboratory have shown that low-level laser energy may produce prompt reduction in isometric tension of vascular smooth muscle. The present study was designed to extend these previous in vitro findings to an in vivo model and thereby investigate the hypothesis that laser light delivered percutaneously in vivo could successfully reverse arterial spasm. METHODS AND RESULTS: Spasm defined as greater than 50% reversible reduction in luminal diameter persisting for greater than or equal to 5 minutes was successfully provoked by injection of histamine (100-400 micrograms/kg) in 13 arteries among 10 atherosclerotic Yucatan microswine; the magnitude of histamine-induced vasoconstriction was then documented angiographically by repeated injections of contrast media for as long as 30 minutes (controls). After return of angiographic luminal diameter to baseline, spasm was reproduced with a second injection of histamine into the same artery. Representative wavelengths generated by ultraviolet (UV), visible, and infrared lasers were then delivered percutaneously via conventional fiberoptics to the site of spasm, and angiographic assessment was repeated for as long as 30 minutes (treatment trial). In three arteries treated with UV (351 nm) light from an excimer laser, angiographic luminal diameter narrowing decreased from 100% to 23.9%, 50.0% to 9.3%, and 76.0% to 42.3%, respectively. The magnitude of laser-induced increase in luminal diameter was 50.2 +/- 22.7%, which was significantly greater than the magnitude of relaxation observed spontaneously during the control trials (10.9 +/- 9.8%, p = 0.02). Visible light from a helium-neon (632 nm) laser accomplished complete reversal of histamine-induced spasm in two of four arteries; in the remaining two arteries, luminal diameter narrowing percentages were reduced from 57.0% to 20.0% and from 76.5% to 30.8%, respectively. The magnitude of helium-neon laser-induced relaxation (55.8 +/- 17.9%) was again significantly greater than that observed during the control trials (0.9 +/- 1.9%, p = 0.01). Finally, infrared irradiation from a diode-pumped neodymium:yttrium aluminum garnet (1,064 nm) laser decreased histamine-induced luminal diameter narrowing in three arteries from 100% to 21.4%, 56.0% to 8.7%, and 68.3% to 35.3%, respectively. The magnitude of infrared laser-induced improvement in luminal diameter narrowing was 53.0 +/- 23.3%, which was significantly greater than that observed during the control trials (12.9 +/- 10.7%, p = 0.01). In three additional arteries, fiberoptic sham trials (without laser irradiation) failed to produce relaxation of histamine-induced spasm. CONCLUSIONS: These findings document for the first time that light-induced relaxation of vascular smooth muscle, previously documented in vitro, may be reproduced in vivo.
BACKGROUND: The pathological consequences of cardiovascular laser irradiation have been studied extensively in vitro. Previous in vivo studies of laser-induced injury have included analyses of acute and/or chronic findings in experimental animals. Little information, however, is available regarding the acute effects of laser irradiation of human vascular tissues in vivo. METHODS AND RESULTS: To determine the acute pathology resulting from laser irradiation of human vascular tissue in vivo, specimens retrieved from 23 patients by directional atherectomy immediately after laser angioplasty (19 peripheral and four coronary) were examined by light microscopy. Of the 23 patients, three (13.0%) were treated with a metal-capped ("hot-tip") fiber coupled to a continuous-wave neodymium:yttrium-aluminum-garnet (Nd:YAG) laser using up to 18 W power and 18-305 seconds of cumulative exposure time; in all three patients (100%), thermal injury, including frank charring several cell layers thick, was seen along the luminal borders of the atherectomy specimen. In eight of the 23 patients (34.5%), laser angioplasty was performed using a 250-microseconds holmium:YAG laser at fluences up to 2,300 mJ/mm2, a repetition rate of 5 Hz, and 25-200 seconds of cumulative exposure; in seven of eight patients (85.5%), the atherectomy specimen showed signs of vacuolar injury consisting of central and satellite Alcian-blue-negative vacuoles. In two patients (25.0%), there was a "smudged" or "shredded" edge, whereas in one patient, frank signs of thermal injury were observed. Finally, in 12 of the 23 patients (52.2%), laser angioplasty was performed using a 120-nsec excimer laser at fluences up to 60 mJ/mm2, a repetition rate of 25 Hz, and a cumulative exposure time of 21-315 seconds. Pathological findings among these 12 patients were limited to nine patients (75%) in whom a weakly basophilic, smudged, and/or shredded appearance approximately one cell layer thick was observed along the luminal border of the atherectomy specimen and two patients (16.7%) with small foci of vacuolar injury. None of the atherectomy specimens retrieved after excimer laser angioplasty disclosed signs of thermal injury. CONCLUSIONS: These findings document that acute pathological alterations resulting from in vivo laser angioplasty are variable, depending on the laser source used, and are similar to that predicted by experimental studies performed previously in vitro. The prognostic implications of these varying pathological features remain to be clarified.
BACKGROUND: Previous studies regarding the mechanism by which balloon angioplasty increases luminal patency have generally used animal models or postmortem specimens from occasional fatal cases of angioplasty performed in human patients. In either case, conclusions regarding participatory mechanisms have relied exclusively on nonserial, postangioplasty histopathological examination. METHODS AND RESULTS: In the present study, intravascular ultrasound examination was performed before and after balloon angioplasty in 40 consecutive patients with iliac artery stenoses. The areas of the arterial wall, plaque, lumen, and areas resulting from angioplasty-induced plaque fractures were measured immediately after angioplasty in vivo and compared with findings recorded immediately before angioplasty. Angioplasty increased luminal cross-sectional area (CSA) from 11.5 +/- 0.6 mm2 before angioplasty to 25.4 +/- 1.2 mm2 after angioplasty (p = 0.0001). CSA of the portion of the postangioplasty neolumen contained within angioplasty-induced plaque fractures measured 10.0 +/- 0.8 mm2; the neolumen excluding the area contributed by these plaque fractures measured 15.4 +/- 0.8 mm2. Thus, the area contained within plaque fractures accounted for 10.0 mm2 (71.9%) of the 13.9-mm2 increase in luminal CSA after angioplasty. Analysis of CSA occupied by atherosclerotic plaque disclosed that plaque CSA decreased from 33.8 +/- 1.8 mm2 before angioplasty to 22.5 +/- 1.5 mm2 after angioplasty (p = 0.0001). Plaque CSA was thus reduced ("compressed") by 11.3 +/- 1.1 mm2. Total artery CSA increased ("stretched") slightly from 45.3 +/- 2.6 mm2 before angioplasty to 47.8 +/- 2.0 mm2 after angioplasty (p = 0.0025). CONCLUSIONS: In vivo analysis of iliac stenoses by intravascular ultrasound immediately before and after angioplasty demonstrates that plaque fractures and "compression" of atherosclerotic plaque are the principal factors responsible for increased luminal patency resulting from balloon angioplasty. "Stretching" of the arterial wall provides an additional, but minor, contribution.
The possibility of using an exclusively percutaneous strategy to deliver foreign DNA to normal and balloon-dilated atherosclerotic arteries was studied by analysis of transfection efficiency in a rabbit model. A total of 22 external iliac arteries from 22 rabbits (10 normal and 12 atherosclerotic) were transfected with a solution of luciferase expression vector plasmid and liposome, using a dual balloon-catheter system. Analysis of the transfected segments revealed luciferase activity in 10 of the 22 arteries (4/10 normal vs 6/12 balloon-injured atherosclerotic, P = NS); no activity could be detected in the contralateral limb arterial segments used as controls. Luciferase activity levels in successfully transfected segments measured 4.10 +/- 1.19 (m +/- SEM) Turner light units (TLU), with 3.03 +/- 1.16 TLU found in normals vs 4.81 +/- 1.87 TLU in balloon-injured atherosclerotic arteries (P = NS). In situ hybridization of successfully transfected atherosclerotic sections showed expression of the luciferase gene mRNA from rare cells (less than 1/1,000) limited to the neointimal lesion. Thus, expression of new genetic material may be achieved in both normal and balloon-dilated atherosclerotic arteries following an exclusively percutaneous approach. The low efficiency of the current delivery strategy, however, represents a potential limitation that must be improved if this strategy is to be applied as a therapeutic approach to human vascular disease.
Human atheromata obtained in vivo were used to test the hypothesis that transforming growth factor-beta 1 plays a role in the development of vascular restenosis. We analyzed 28 specimens from patients with primary atherosclerotic or restenotic lesions; 26 of these were obtained by directional atherectomy and 2 at the time of coronary bypass surgery. Seven control tissues included operatively excised segments of human internal mammary artery, myocardium, and unused portions of vein graft obtained intraoperatively. From these 35 specimens, 210 sections were examined using in situ hybridization. Measurement of silver grains/nucleus disclosed that expression of transforming growth factor-beta 1 mRNA was highest in restenotic tissues (P < 0.001 vs. primary atherosclerotic tissues) and lowest in nonatherosclerotic (control) tissues. In cultures of human vascular smooth muscle cells grown from explants of internal mammary artery, expression of mRNA for transforming growth factor-beta 1 was significantly greater in subconfluent than in confluent smooth muscle cells (P = 0.05). Transforming growth factor type-beta III receptor was expressed in cell cultures and undetectable in the tissue specimens. Sections taken adjacent to those studied by in situ hybridization were examined by immunohistochemistry using antibodies against transforming growth factor-beta 1 and alpha-actin (as a marker for smooth muscle cells) and disclosed transforming growth factor-beta 1 in smooth muscle cells present in these sections. These findings are consistent with the concept that transforming growth factor-beta 1 plays an important role in modulating repair of vascular injury, including restenosis, after balloon angioplasty.
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.
Laser-induced fluorescence has been used in conjunction with angiography for laser angioplasty guidance. The effect of radiopaque contrast media on the excitation and detection of arterial fluorescence has not been previously reported. Accordingly, fluorescence emission spectra from human coronary artery necropsy specimens (n = 7) during excitation with pulsed excimer laser excitation (308 nm) was examined before and after the addition of three different contrast media, sodium and meglumine diatrizoate, sodium and meglumine ioxaglate, and iopamidol. A decrease in overall fluorescence intensity was observed at all wavelengths for each contrast agent examined. The decrease in intensity of fluorescence emission was more marked at wavelengths less than 410 nm than at wavelengths above 425 nm. Similar effects were observed for contrast media diluted with whole blood. Absorption spectra for all three contrast media demonstrated absorption in the ultraviolet centered around 240 nm. We conclude that preferential absorption in the ultraviolet range by contrast media interferes with the excitation and detection of laser-induced fluorescence; use of visible light excitation may obviate interference with laser-induced fluorescence analysis of plaque.
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Among the initial 492 patients who underwent balloon aortic valvuloplasty as part of the Mansfield Investigational Device Exemption Protocol, 31 (6.3%) had acute catastrophic complications. These included ventricular perforation in nine (1.8%), seven women and two men; six cases (67%) involved serial balloon inflations and seven (78%) also involved dual balloon inflations. In six (67%) of the nine patients perforation was fatal. In four patients studied at necropsy, the perforation involved the base of the lateral left ventricular free wall. Pericardiocentesis was performed in five patients, three of whom survived with (one patient) or without (two patients) operative repair. Acute, severe aortic regurgitation developed in four patients (0.8%), all women. None had significant regurgitation before valvuloplasty; dual balloons were used in two of the four. All three patients who underwent emergency valve replacement survived. A fourth patient died 2 days after valvuloplasty without operative intervention. Fatal cardiac arrest complicated balloon aortic valvuloplasty in 13 patients (2.6%), including 7 with cardiogenic shock and 4 with refractory ventricular arrhythmias. Of the seven with shock, four had been treated with serial balloon inflations; dual balloons were used in three. In two of three patients studied at necropsy, the aortic valve was observed to be congenitally bicuspid. A fatal cerebrovascular accident occurred in two patients (0.4%); it was hemorrhagic in one, embolic in another. Both patients were treated with serial (including one dual) balloon inflations. Limb amputation was required in three patients (0.6%), two women and one man; in two patients amputation was above the knee, in the third patient it was limited to two toes.(ABSTRACT TRUNCATED AT 250 WORDS)
Cocaine abuse is now firmly associated with several cardiac complications. Acute myocardial infarction is the best documented of these complications and appears to result from cocaine-induced coronary arterial spasm. Myocarditis and/or cardiomyopathy have also been reported in a smaller number of patients. Finally, life-threatening cardiac arrhythmias may also result from cocaine abuse.
BACKGROUND: We investigated the hypothesis that an ultrasound transducer positioned within an angioplasty balloon could be used to perform quantitative assessment of arterial dimensions before and after percutaneous transluminal angioplasty (PTA) and to identify certain mechanical alterations consequent to PTA, including vascular wall recoil and the initiation of plaque fractures. METHODS AND RESULTS: A combination balloon-ultrasound imaging catheter (BUIC) that houses a 20-MHz ultrasound transducer within and halfway between the proximal and distal ends of an angioplasty balloon was used to perform PTA in 10 patients with peripheral vascular disease. Each PTA site was also evaluated before and after PTA by standard (nonballoon) intravascular ultrasound (IVUS) technique. In eight patients in whom satisfactory images were recorded with the BUIC before PTA, luminal cross-sectional area (XSA) of stenotic sites (0.10 +/- 0.01 cm2) did not differ significantly from measurements of XSA by IVUS (0.09 +/- 0.01 cm2, p = NS). Likewise, minimum luminal diameter (Dmin) measured by BUIC (0.34 +/- 0.02 cm) was similar to that measured by IVUS (0.33 +/- 0.01 cm, p = NS). In nine patients in whom satisfactory images were recorded with the BUIC after PTA, XSA measured by BUIC (0.29 +/- 0.03 cm2) did not differ significantly from XSA measured by IVUS (0.30 +/- 0.03 cm2, p = NS). Dmin measured by BUIC after PTA (0.57 +/- 0.02 cm) was also similar to Dmin measured by IVUS (0.57 +/- 0.03 cm, p = NS). After PTA, XSA and Dmin measured immediately after deflation were significantly less than balloon XSA and diameter at full inflation, indicating significant elastic recoil of the dilated site. For the nine patients in whom post-PTA images were satisfactory for quantitative analysis, including four patients in whom recoil was 39%, 46%, 50%, and 61%, percent recoil measured 28.6 +/- 7.2%. Finally, plaque fractures were identified on-line in six of 10 patients (60%); in each case, initiation of plaque fracture was observed at inflation pressures of 2 atm or less. CONCLUSIONS: The results of this preliminary human investigation indicate that an ultrasound transducer positioned within an angioplasty balloon can be used to perform quantitative and qualitative analyses of lumen-plaque-wall alterations immediately preceding, during, and immediately after PTA in patients with peripheral vascular disease.