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Biomedical subjects

J M Isner

Publications and source records attributed to J M Isner.

At least 19 recordsLinked to original sources
PubMed1992

Smooth muscle cell outgrowth from human atherosclerotic plaque: implications for the assessment of lesion biology.

OBJECTIVES: The purpose of this study was to determine whether the kinetics of smooth muscle cell outgrowth from in vitro explants of human atherosclerotic tissue is dependent on the nature of the atherosclerotic lesion in vivo. BACKGROUND: The use of techniques for percutaneous in vivo extraction of atherosclerotic plaque has provided the opportunity to study human atheroma-derived smooth muscle cells in culture. However, because of cell selection and changes in phenotype, in vitro findings may not always reflect the biologic properties of the vessel wall, particularly if cells are in culture for prolonged periods. In contrast, studies with nonhuman cells have suggested that the rate at which cells grow out of tissue explants is closely related to the status of the cells in vivo. METHODS: Atherosclerotic tissue from 41 lesions, including primary plaques (from peripheral arteries and venous bypass conduits) and restenotic lesions (from peripheral arteries and venous conduits) were divided into a total of 1,596 fragments and placed in culture on fibronectin-coated wells. Explant outgrowth was scored over the ensuing 1 month to determine the prevalence and time course of smooth muscle cell outgrowth and the total cellular accumulation. RESULTS: Explant fragments from 40 (98%) of the 41 lesions yielded an outgrowth of smooth muscle cells, confirmed by immunocytochemistry. The mean proportion of adherent explant fragments yielding outgrowth, per lesion, was 69 +/- 4% and was higher in restenotic tissue (81 +/- 3%) than in primary tissue (56 +/- 6%, p < 0.001). For primary lesions, initiation of outgrowth was half-maximal by 8.7 +/- 0.4 days; for restenotic explants, initiation of outgrowth was considerably faster (half-maximal by 5.9 +/- 0.6 days, p < 0.001). Similarly, accumulation of smooth muscle cells around an explant was significantly greater for restenotic lesions (2,791 +/- 631 cells/explant) than for primary lesions (653 +/- 144 cells/explant, p < 0.01). Labeling of first-passage cells with [3H]-thymidine indicated that cells from restenotic lesions had a 1.3-fold greater incorporation rate than did cells from primary lesions (p < 0.05). CONCLUSIONS: Smooth muscle cells may be reliably cultivated by explant outgrowth from a variety of human atherosclerotic plaque types obtained intraoperatively or percutaneously. The kinetics of outgrowth from restenotic tissue is distinctly different from that of outgrowth from primary tissue, suggesting a relation between the in vitro outgrowth behavior and the biology of the lesion in vivo. Assessment of smooth muscle cell outgrowth from human atherosclerotic plaque may thus represent a practical and reliable means to investigate the biologic behavior, including growth characteristics, of individual atherosclerotic lesions from human subjects. This technique may also offer a suitable assay system for evaluating therapies designed to inhibit lesion proliferation.

Analysis of Variance↗
PubMed1992

Three-dimensional reconstruction of human carotid arteries from images obtained during noninvasive B-mode ultrasound examination.

Previous investigators have demonstrated that B-mode ultrasonography can provide high resolution images of the carotid arteries. When combined with Doppler flow measurements, quantitative estimates of luminal narrowing may also be obtained. B-mode imaging is limited, however, in its ability to provide a composite view of the vessel wall, lumen and plaque. Spatial relations between structures visualized in individual frames must be inferred from repeated transducer passes over the designated site, or repeated review of recorded images, followed by a "mind's eye" reconstruction. Three-dimensional (3-D) reconstruction of serially recorded cross-sectional images from current B-mode systems represents a possible solution to this limited spatial display that preserves detail regarding vessel wall pathology. Accordingly, computer-based automated 3-D reconstruction was used to generate a tangible format with which to assess and compare serially and transcutaneously recorded 2-dimensional (2-D) B-mode images of the carotid arteries. One or more timed sweep recordings of the 2-D B-mode examination were obtained from 5 patients for 3-D reconstruction. In all cases, satisfactory 3-D reconstruction was accomplished in three 3-D formats: cylindrical, sagittal and lumen cast. Sagittal 3-D reconstruction provided information regarding pathologic alterations within the arterial wall. Experience with the cylindrical mode suggests that this 3-D format, particularly when the reconstructed vascular segment is hemisected, is optimally suited for those cases in which direct inspection of luminal topography is of special interest. The lumen cast display, used with a recently validated edge-detection algorithm, may enhance the use of B-mode ultrasound for assessment of luminal cross-sectional area.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

A new balloon-expandable tantalum coil stent: angiographic patency and histologic findings in an atherogenic swine model.

The angiographic patency and histologic characteristics of a new balloon-expandable tantalum stent were studied after implantation intervals ranging from 1 to 32 weeks in atherogenic miniature swine peripheral and coronary arteries. Stents were placed in 34 arteries (10 coronary and 24 iliac arteries) in a total of 13 swine. Two swine died within 24 h of stent implantation. Follow-up angiography was performed before death was induced in 11 swine (8 coronary and 19 iliac arteries) and revealed 100% patency without evidence of lumen stenosis, thrombosis or migration of the stents. The neointimal thickening was maximal at 4 weeks after stent implantation and was at its minimum at 32 weeks after implantation with reendothelialization of the stents generally complete at that time. An advantage of this balloon-expandable device is its inherent longitudinal flexibility. The coil configuration allowed the nondeployed stent to negotiate acute bends in coronary arteries to reach the site of implantation and also allowed the deployed stent to conform to the natural contour of tortuous coronary arteries. The tantalum device was remarkable for its radiographic visibility, which greatly aided its placement under fluoroscopic guidance. This study demonstrates this stent's ease of implantation, excellent patency rate and absence of restenosis due to neointimal proliferation for up to 8 months in this atherogenic swine model.

Angioplasty, Balloon, Coronary↗
PubMed1992

Factors influencing immediate results, complications, and short-term follow-up status after Inoue balloon mitral valvotomy: a North American multicenter study.

Clinical trials with the Inoue mitral valvotomy balloon have recently begun in the United States. We assessed the effects of 17 demographic, echocardiographic, procedural, and hemodynamic variables on the immediate results, complications, and short-term follow-up of 200 patients in 15 centers undergoing valvotomy with this device. The study population had a mean age +/- SD of 53 +/- 15 years, and the total echocardiographic score was 7.2 +/- 2.4. Valvotomy was technically successful in 96.5% of procedures and increased the mean mitral valve area from 1.0 +/- 0.3 to 1.8 +/- 0.7 cm2 (p less than 0.001); 72% had an increase in valve area greater than or equal to 50%, and 67% had a final area greater than or equal to 1.5 cm2. Major procedural complications included cardiac tamponade during transseptal puncture (1.0%), systemic embolism (1.5%), and severe mitral regurgitation (2.4%); there were no procedural deaths and one hospital death. Multivariate analysis identified the absence of prior surgical commissurotomy and younger age as significant predictors of the gain in mitral valve area, but the correlation coefficients were low. Although the absence of subvalvular disease on echocardiograms was a predictor of a final valve area greater than or equal to 1.5 cm2, the total echocardiographic score did not correlate well with the immediate outcome (r = 0.01, p = NS). No variable was identified as predictive of restenosis, which occurred according to echocardiographic criteria in 14 of 66 (21%) patients evaluated 6 months after valvotomy. Good hemodynamic results with valvotomy were achieved in the majority of patients with low complication rates by many investigators with the use of the Inoue balloon device.(ABSTRACT TRUNCATED AT 250 WORDS)

Balloon Occlusion↗
PubMed1992

Failure of angiography to accurately depict the extent of coronary artery narrowing in three fatal cases of percutaneous transluminal coronary angioplasty.

The angiographic and pathologic findings are described in three patients who died less than 24 h after failed percutaneous transluminal coronary angioplasty. In two of the three patients, coronary angiography performed before angioplasty disclosed apparently focal lesions in the left anterior descending and right coronary arteries. In these two patients quantitative angiographic analysis disclosed a minimal lumen cross-sectional area of 1.82 and 0.47 mm2, respectively, at the sites of apparently focal stenoses before angioplasty; corresponding percent lumen area narrowing measured 84% and 91%, respectively, by quantitative angiography at these two sites. In the third patient, coronary angioplasty was undertaken when the patient developed spontaneous occlusion of the right coronary artery several hours after diagnostic angiography. Retrospective quantitative angiographic analysis of the right coronary artery revealed a minimal lumen cross-sectional area of 1.14 mm2, with 85% lumen area narrowing at the site of subsequent total occlusion and angioplasty. In each of these three patients, necropsy examination disclosed that the distribution of coronary narrowing in the artery treated by angioplasty was in fact not focal; rather, in each of these three patients, the artery treated by angioplasty, as well as the extramural coronary arteries not treated by angioplasty, were severely narrowed by diffusely distributed atherosclerotic plaque. The angiographic and necropsy findings in these three patients document that coronary narrowing that remains occult by virtue of diffuse distribution may complicate evaluation of patients being considered for coronary angioplasty.

Adult↗
PubMed1992

Obstruction of right ventricular outflow tract caused by intracavitary metastatic disease: analysis of 14 cases.

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.

Adenocarcinoma↗
PubMed1992

Human coronary and peripheral arteries: on-line three-dimensional reconstruction from two-dimensional intravascular US scans. Work in progress.

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.

Adult↗
PubMed1992

Effect of valve deformity on results and mitral regurgitation after Inoue balloon commissurotomy.

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.

Adult↗
PubMed1992

Evidence implicating nonmuscle myosin in restenosis. Use of in situ hybridization to analyze human vascular lesions obtained by directional atherectomy.

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.

Arteriosclerosis↗
PubMed1992

Percutaneous delivery of low-level laser energy reverses histamine-induced spasm in atherosclerotic Yucatan microswine.

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.

Animals↗
PubMed1992

In vivo assessment of vascular pathology resulting from laser irradiation. Analysis of 23 patients studied by directional atherectomy immediately after laser angioplasty.

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.

Aged↗
PubMed1992

How does angioplasty work? Serial analysis of human iliac arteries using intravascular ultrasound.

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.

Aged↗