Biomedical subjects

U Welsch

Publications and source records attributed to U Welsch.

At least 55 records · Page 3Linked to original sources

PubMed1996

Morphological variability of smooth muscle cells in human nasal swell bodies.

The complex functional behavior of nasal swell bodies is still not completely understood. In the present study the histology of the vessels involved in the swelling mechanism is examined and the ultrastructural appearances described of the different types of smooth muscle cells located in the vascular wall of swell bodies in the human inferior turbinate. Even though the majority of smooth muscle cells of the nasal swell bodies showed a normal, elongated appearance comparable to other smooth muscle cells elsewhere in the body, a variety of cells with atypical shapes could be detected that have not been described previously in vessels of the nasal mucosa. The diameters of the smooth muscle cells in general were strikingly variable. The individual smooth muscle cells were surrounded by a basal lamina that was occasionally disrupted or doubled. Myoblasts were separated by a connective tissue space containing collagen fibrils, mature elastin fibers and bundles of microfibrils. The latter two types of fibers and fibrils occurred mainly in the outer parts of the muscular coat. The endowment of cytoplasmic components was similar in all smooth muscle cells of the vascular wall in the swell bodies. These findings indicate that the specific feature of smooth musculature presumably resides in the unusual morphological variability of the single cells present, as well as in the striking heterogeneity of the arrangement of bundles of these cells in the vascular wall.

Connective Tissue↗

PubMed1996

Lectins and antibodies against blood-group antigens as tools for studying the cellular source of glycoproteins in human bronchial fluid: a comparison of morphological and biochemical observations.

We used nine lectins and three antibodies directed against ABO blood-group antigens in morphological and Western-blot experiments to investigate the source of secretory products of human large airways. In tissue sections, the lectins from Griffonia simplicifolia (type I B4), Dolichos biflorus, and Helix pomatia, and the antibodies to the A, B, and/or H-antigen bound to mucous gland cells and to goblet cells; the binding of these substances was dependent on secretor status and ABO blood group. The lectins from Arachis hypogaea, Lens tetragonolobus, Ulex europaeus (type I), Triticum vulgaris, and Sambucus nigra bound to these cell types, regardless of ABO blood group. Serous cells of the tracheal and bronchial glands were stained by the lectins from Canavalia ensiformis, T. vulgaris, Lens tetragonolobus, S. nigra, and U. europaeus (type I). On Western blots of bronchial proteins, the mucins in the high molecular weight region exhibited the same lectin and antibody binding as the mucous gland cells and the goblet cells in the histochemical preparations. The low molecular weight bands were characterized by similar lectin- and antibody-binding properties as the serous gland cells. Thus, mature mucins in the large airways are produced only in the mucous cells of the glands and in the goblet cells, whereas fully glycosylated low molecular weight glycoproteins originate only from the serous cells of the glands.

ABO Blood-Group System↗

PubMed1996

Total replacement of the mitral apparatus with a stentless, chordally supported mitral valve allograft: an experimental study.

Mitral valves, including the papillary muscles, were harvested from freshly slaughtered sheep and implanted in 10 recipient growing sheep. A strip of ovine pericardium was used to reinforce the anulus and a patch of expanded polytetrafluoroethylene was used to cover the donor papillary muscle. In four valves the natural chordae tendineae at the anterior cusp were supported by two pairs of 5-0 expanded polytetrafluoroethylene sutures. At the beginning of the experiment two animals died early of valve incompetence. Another animal had to be put to death because of paraplegia after extracorporeal circulation and one died on postoperative day 41 of endocarditis. Six sheep were electively put to death, five after 153 +/- 8 days and one after 43 days. At the time of follow-up, a complete hemodynamic study including echocardiography and stress testing was performed. Heart rate at rest was 91 +/- 14 beats/min, left ventricular systolic pressure 96 +/- 20 mm Hg, left ventricular end-diastolic pressure 11 +/- 5 mm Hg, cardiac output 2.04 +/- 0.40 L/min, and the mean transvalvular pressure gradient was 4.9 +/- 2.8 mm Hg as measured by cardiac catheterization. Echocardiography showed excellent movement of all valve components. However, minor regurgitation was evident in one case. Gross morphologic characteristics showed good healing at the anulus and host papillary muscle; in one case there was a rupture of one small first-order chorda. On radiography no signs of calcification were evident. Light microscopy revealed minor to moderate collagen degeneration in all valve components. However, on electron microscopy the presence of numerous fibroblasts within the long-term implants indicated the biosynthesis of new collagen. In summary, allograft mitral valve replacement seems to be a promising procedure if the chordae tendineae are reinforced by expanding polytetrafluoroethylene sutures.

Animals↗

PubMed1996

Local photodynamic therapy reduces tissue hyperplasia in an experimental restenosis model.

Local photodynamic therapy may have potential in preventing myointimal hyperplasia after angioplasty. In this study, the effect of photodynamic therapy was evaluated in an experimental model of restenosis. Standardized unidirectional arterial injury with a directional atherectomy catheter was performed in porcine arteries. Animals were randomly allocated to four groups: group 1, unidirectional injury only; group 2, injury followed by local delivery of photosensitizer; group 3, injury followed by local exposure to monochromatic light; and group 4, where injury was followed by local drug delivery of photosensitizer and subsequent exposure to light (photodynamic therapy). Seven, 14 or 21 days after treatment, all experimental vessels were excised, fixed and processed for histology. An inflammatory and myoproliferative response was observed after injury in vessels from groups 1, 2 and 3. In group 4, after injury followed by photodynamic therapy, the myoproliferative response was significantly reduced. Thus, in this study, tissue hyperplasia after unidirectional injury was effectively suppressed by photodynamic therapy.

Animals↗

PubMed1996

Stimulation of thyroid cell proliferation by epidermal growth factor is different from cell growth induced by thyrotropin or insulin-like growth factor I.

Isolated intact porcine thyroid follicles free of contaminating single cells were embedded in "Matrigel", which is a gel-forming basement membrane preparation containing mainly collagen type IV, laminin, heparan sulfate proteoglycans and entactin. Follicles were treated with different growth factors: thyrotropin (TSH), insulin-like growth factor I (IGF-I), epidermal growth factor (EGF) or transforming growth factor beta. Cell proliferation was quantified by counting cell numbers. Morphological studies were done by photodocumentation and analysis of histology by light and electron microscopy. The thyrocytes had the physiological polarity with follicular cell arrangement, microvilli at the apical membrane, desmosomes and tight junctions. The lumen contained colloid. Iodide organification (10.2 +/- 2.1 vs 26.1 +/- 5.8 pmol/10(6) cells; TSH 0.1 mU/ml) and release of thyroid hormones (thyroxine, 1754 +/- 207 vs 2890 +/- 460 pg/10(6) cells; triiodothyronine, 164 +/- 22 vs 412 +/- 106 pg/10(6) cells; TSH, 1mU/ml) were significantly stimulated by TSH. There was no basal growth rate in serum-free medium but proliferation was slightly stimulated with TSH (1 mU/ml; 149 +/- 19%) and in the same order of magnitude with IGF-I (10 ng/ml; 159 +/- 23%) but without follicle neoformation. In contrast, BGF (1.0-5.0 ng/ml) induced thyrocyte proliferation dose dependently three- to sixfold. With BGF up to 2 ng/ml, buds of new follicles formed surrounding pre-existing follicles. With BGF higher than 3 ng/ml, typical papillary structures developed. Transforming growth factor beta inhibited this dedifferentiated growth. A migration of single cells into the gel was never observed. Thus, three-dimensional culture of isolated thyroid follicles in "Matrigel" provides a tool for investigating the regulation of follicular growth and neoformation close to the in vivo situation.

Animals↗

PubMed1996

[Incidence and localization of apoptosis bodies in human arteriosclerosis lesions].

Increased density of smooth muscle cells is an accepted feature of human restenosis after angioplasty. In addition to migration and proliferation, deregulated forms of programmed cell death may represent pathogenic mechanisms which lead to increased intimal cellularity. The goal of the present study was (i) to demonstrate programmed cell death in human plaque tissue by the detection of apoptotic bodies and to distinguish it from cellular necrosis, (ii) to evaluate the frequency and the localization of apoptotic bodies, and (iii) to compare restenotic and primary lesions for different expression patterns. To this end, coronary and peripheral atherectomy specimens from 14 restenotic and 25 primary lesions were examined by electron microscopy and morphometric analysis. Apoptotic bodies were distinguished from cellular necroses due to distinct morphological features, and were observed extracellularly, isolated or cell membrane-bound, as well as intracellularly in smooth muscle cells and macrophages. The main finding of this study is that hypercellular restenotic tissue from both coronary and peripheral lesions contains fewer apoptotic bodies than hypocellular plaques from primary lesions (p < 0.01 and p < 0.05, respectively). Most importantly, a highly significant, inverse correlation was seen between the density of apoptotic bodies and intimal cellularity (r = -0.67; p < 0.0001). Especially in the extracellular matrix regions, restenotic lesions showed fewer apoptotic bodies (p < 0.001). Again, these plaques exhibited a smaller number of apoptotic bodies with intracellular or membrane-bound localization; however, this observation was without statistical significance compared to primary lesions. For both plaque types, apoptotic bodies were found more frequently (by the factor 4-10) in the presence of smooth muscle cells than with macrophages. With respect to the cellular composition of the plaques, apoptotic bodies were evenly detected in 15-28% of all smooth muscle cells and macrophages. Our results document a considerable intimal density of apoptotic bodies in high-grade human arteriosclerotic lesions and, in addition, reveal nearby smooth muscle cells and macrophages exhibiting intensive phagocytotic capacity. Differences in the density of apoptotic bodies and in cellularity, coincident with an inverse correlation between these determinants, were observed for restenotic and primary tissue. These findings strongly point to deregulated forms of programmed cell death as important pathogenic mechanisms involved in human restenosis.

Aged↗

PubMed1995

Dislocation of the rotating cutter during directional coronary atherectomy: a note of caution.

Directional coronary atherectomy (DCA) has received increased attention, especially as a bail-out procedure after failed balloon angioplasty. However, this technique may also be burdened by severe pitfalls. We report a patient with a balloon-resistant left coronary artery lesion subsequently treated with DCA. Despite its over-the-wire guidance, as the rotating cutter was advanced, it deviated from its intra-housing course and intruded into the vascular wall. Dislocation of the rotating blade was due to pressure from hard plaque tissue. After having carefully pulled back the complete catheter system, a severe spasm of the left main stem occurred, which was reversed by intracoronary nitroglycerine. The final angiography showed a left coronary artery without significant, residual stenosis. The case report underscores that DCA passes must be performed under continuous fluoroscopic control, especially for balloon-resistant lesions because of the unpredictability of DCA-imminent complication.

Atherectomy, Coronary↗

PubMed1995

Histological, histochemical, and ultrastructural investigations on the gastrointestinal system of Antarctic seals: Weddell seal (Leptonychotes weddellii) and crabeater seal (Lobodon carcinophagus).

The morphology of the principal sections of the gastrointestinal system of two Antarctic seals with different dietary habits, namely, the Weddell seal (Leptonychotes weddellii) and the crabeater seal (Lobodon carcinophagus), has been investigated. Histologically examined by light microscopy, the tissue layers of the gastrointestinal tract of both seals are almost identical to those observed in most other mammals and no major differences in principle organization could be found between the two seal species. The ultrastructure of the gastric and intestinal epithelial cells has been examined and is also closely comparable to that of these cells in other mammals; however, Paneth cells have not been found in our material. In general, therefore, adaptations of the gastrointestinal tract to the aquatic environment or the diet are not obvious at the morphological levels of organization studied. Histochemical differences are found between the two closely related species; mucins of the surface epithelium in the stomach of Weddell seals are highly sulfated, while those in the crabeater seal are not. Mucous neck cells in Weddell seals contain acid mucosubstances, while those of crabeater seals contain neutral ones. Goblet cells in the small and large intestine in Weddell seals contain both neutral and acid mucosubstances. Both mucin types are detected in the crabeater seal; however, the mucins of the colon in the crabeater seal are more highly sulfated than those in the Weddell seal. The ratio of goblet cells to enterocytes in the large intestine of crabeater seals is higher than that in Weddell seals.

Acclimatization↗

PubMed1995

A histochemical study of the distribution of lectin binding sites in the developing oocytes of the lancelet Branchiostoma belcheri.

The distribution of carbohydrate moieties in lancelet (Branchiostoma belcheri) oocytes has been studied at different stages of development, using a peroxidase-labeled lectin incubation technique, the PAS-reaction and Alcian Blue staining. Binding sites of 5 lectins, indicating the presence of different sugar moieties (Wheat germ agglutinin (WGA) for N-acetylglucosamine, Concanavalin A (Con A) for glucose/mannose, Helix pomatia agglutinin (HPA) for N-acetyl-D-galactosamine, Ricinus communis agglutinin (RCA-I) for galactose and Ulex europaeus agglutinin (UEA-I) for fucose), were identified and were shown to undergo considerable variation during oocyte development. In the previtellogenic stage, HPA, RCA-I and UEA-I were not identified on the oocyte surface, but WGA and Con A gave strongly positive reactions at this site. In the cytoplasm, 4 lectins (Con A, HPA, RCA-I and UEA-I) gave a weak or moderate reaction, and Con A was also observed in the perinuclear region. In vitellogenic oocytes, these 4 lectins were found to also bind to the nuclear envelope, karyoplasm and nucleolus, and, with the exception of Con A, could also be found in the nuclei of more mature stages. The cytoplasmic yolk granules and Golgi vesicles of the vitellogenic oocyte, were moderately positive for Con A, HPA, RCA-I and UEA-I, but HPA, RCA-I and UEA-I were only weakly bound at the oocyte surface. In mature oocytes, all 5 lectins bound moderately or strongly to yolk granules and cell surface. HPA, RCA-I and UEA-I bound moderately or strongly to various nuclear compartments.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Ultrastructural localization of glycosaminoglycans in human gingival connective tissue using cupromeronic blue.

Human gingiva was stained with cupromeronic blue according to Scott's critical electrolyte concentration technique in order to localize glycosaminoglycans (GAG) in the electron microscope. Identification was performed by digestion with chondroitinase AC, ABC and heparinase. The GAG were localized in three compartments of the connective tissue: the supra-alveolar fiber apparatus, the loose connective tissue and the basement membranes. In the supra-alveolar fiber apparatus, consisting mainly of densely packed parallel collagen fibrils, dermatan sulfate GAG are regularly attached to the d-band of the collagen fibrils. The precipitates (6-7 nm in diameter) aggregate to thicker precipitates (up to 16 nm), thus possibly providing stability to the fiber system. In the loose connective tissue with sparse collagen fibrils dermatan and chondroitin sulfate GAG form very large precipitates (up to 30 nm in diameter and 400 nm length) which interconnect the few collagen fibrils. The basement membranes of the epithelium and capillary endothelium contain heparan sulfate GAG as fine precipitates (4-6 nm in diameter) which form a meshwork. These findings are consistent with the Scott model (1) for the interactions among glycans and glycans and collagen fibrils in connective tissues.

Basement Membrane↗

PubMed1995

[Ultrastructural characteristics of cellular reaction to experimental catheter-induced lesions of arterial blood vessels].

UNLABELLED: After angioplasty, restenosis remains the major drawback of the procedure with an incidence of between 20-40%. It is a matter of concern whether the cellular alterations start immediately after directional atherectomy (DA) and if they are dependent on the depth of the lesion. METHOD: Cellular alterations immediately after DA were investigated using peripheral atherectomy in normal vessels of 30 pigs (A. femoralis, A. carotis communis). DA was used to remove material. The arteries were assigned to two groups according to the depth of vessel injury. (Group 1: lesions to the intima; Group 2: lesions to the media.) 68 arteries with 41 intimal and 27 media lacerations were excised 4 to 24 hours later and processed for transmission electron microscopy, histology and immunohistochemistry. RESULTS: Immediately after DA, thrombus formation at the site of the altered segment was found. A transient infiltration of polymorphonuclear leukocytes (PMN) occurred, especially if the media was lacerated, followed by the transformation of contractile smooth muscle cells (SMC) into the synthetic subtype. A marked myoproliferative response was found in Group 2 whereas only moderate tissue hyperplasia was seen in Group 1. CONCLUSION: The present data provides evidence that cellular alteration of the atherectomized vessel begins immediately after atherectomy. Subsequent to the initial temporary PMN infiltration, an activation of local SMC occurs at a very early stage. These effects and, in particular, a myoproliferative response were found lesions injured the internal elastic membrane, while only minor effects were seen when the lesion affected the intimal layer.

Animals↗

PubMed1994

Transplantation of fetal adrenal glands in syngeneic rat strains.

In a syngeneic rat model we investigated the feasibility of fetal adrenal gland transplantation into adult recipient animals. We determined the optimal site of graft implantation by morphological criteria. Transplantation into the omentum majus proved superior to transplantation underneath the fascia of the rectus abdominis muscle possibly due to superior access to vascular supply. We assessed transplant function by sequential determinations of serum corticosterone, aldosterone, sodium and body weight. We compared rats which received syngeneic fetal adrenal transplants and underwent excision of their own adrenal glands four weeks thereafter to control animals without adrenalectomy or transplantation and to adrenalectomized animals without prior transplantation. The total study period was 16 weeks. Whereas all adrenalectomized rats without prior transplantation died within 2 weeks, all the animals which had received fetal adrenal grafts survived. Their serum sodium remained within normal limits. Weight gain and serum corticosterone levels were decreased when compared to control animals. Aldosterone levels dropped intermittently but had normalized by 16 weeks. We conclude that fetal adrenal grafts may be able to substitute for the animals' own adrenal glands in the syngeneic model.

Adrenal Glands↗

PubMed1994

[Mechanisms of re-stenosis after angioplasty].

Restenosis post angioplasty is a segmentally limited, wound healing response to a circumscript traumatization of the vascular wall associated with the therapeutic intervention, which also comprises residual or recoiling plaque components at the time of initial revascularization. Studies with animal models and the analysis of human plaque tissue harvested by autopsy or atherectomy indicate a cascade-like course of this wound healing reaction, in which initially different cell types such as thrombocytes, endothelial cells, monocytes/macrophages and smooth muscle cells (SMCs), later predominantly SMCs are involved. In the first phase of inflammation, angioplasty as a multifactorial stimulus induces a sequence of (a) destruction of endothelial and subendothelial structures, (b) traumatization of medial regions with rupture of the internal elastic lamina, (c) exposition of thrombogenic factors such as collagen or tissue factor, (d) stretching of smooth muscle cells with subsequent expression of proto-oncogens (c-fos, c-myc, c-myb), (e) release of growth factors from cells of the bloodstream, endothelial cells and SMCs by direct traumatization and segmental thrombus formation, and (f) thrombin production with autocatalytic activation of the SMC thrombin receptor. Overlapping the inflammation period, granulation begins 3 days after angioplasty. Proteinases such as plasmin as well as collagenases induce the disintegration of extracellular matrix structures, thereby modulating plaque formation, and lead to an organelle-rich SMC phenotype within the intima and media. The phenotypic alteration of SMCs is considered to be the prerequisite for mitogenic and migratory stimulation. This stage shows different expression patterns of growth factors and their receptors; however, there is only limited knowledge about spatiotemporal and maximal expression as well as their coordination for human vascular wall tissue (PDGF, PDGF-R, EGF-R, FGF, FGF-R, TGF-beta). Overlapping with the granulation period, induction of different components of the extracellular matrix occurs 1-2 weeks after angioplasty, possibly mediated by TGF-beta (phase of matrix formation). Smooth muscle cells produce and secrete matrix proteins such as tenascin, fibronectin, collagens and proteoglycans, and thereby induce a marked increase of the neointimal plaque volume. Angiographic restenoses of coronary and peripheral arteries histologically exhibit tissue with high cellularity (> 500 cells/mm2), associated with SMC activity markers such as PCNA or NMMHC-B. Proliferative and migratory activities of these cells in vitro are augmented by a factor of 2 to 3 as compared to those from chronic primary lesions. Transmission electron microscopic analysis proves that within the media a nearly complete re-differentiation of SMCs occurs, whereas intimal SMCs persist in the intermediate phenotype.(ABSTRACT TRUNCATED AT 400 WORDS)

Angioplasty, Balloon, Coronary↗

PubMed1994

Colchicine antagonizes the activity of human smooth muscle cells cultivated from arteriosclerotic lesions after atherectomy.

AIM: Proliferative, migratory, and secretory activities of vascular smooth muscle cells are functional determinants of human atherosclerotic plaque and restenosis formation. The present study was designed to examine the effects of interfering with these processes using drugs. MATERIALS AND METHODS: For in-vitro studies of smooth muscle cell activity, arterial smooth muscle cells were cultivated from human plaque tissue excised from 22 coronary and peripheral lesions and treated with the antitubulin colchicine. Smooth muscle cell migratory activity was analyzed by a standardized semi-automatic video system. Transmission electron microscopy was used to examine cytoplasmic structures. RESULTS: Colchicine caused a concentration-dependent decrease in smooth muscle cell proliferative activity at a half-maximal inhibitory concentration (IC50) of 5 nmol/l. Smooth muscle cell migratory activity was reduced by colchicine in a concentration-dependent manner (IC50, 3 nmol/l). Concordantly, transmission electron microscopy revealed severe disorganization of cytoplasmic structures, especially of organelles, indicating metabolic activation. CONCLUSIONS: In-vitro studies with human smooth muscle cells from arteriosclerotic lesions suggest that the antitubulin principle may be useful in producing anti-arteriosclerotic effects, since a pronounced antagonization of smooth muscle cell proliferative, migratory, and secretory processes, indirectly inferred from ultrastructural analysis, was demonstrated with low concentrations of colchicine.

Actin Cytoskeleton↗

PubMed1994

[Pathophysiology and pathobiochemistry of restenosis].

The high rate of restenosis after percutaneous transluminal angioplasty obviously depends on multiple factors. Predictors for the clinical outcome seem to be the selection of lesion morphology, the acute result and the biological vessel response in the first months after treatment. Thrombus formation and recoil have been considered to be pivotal events. Thus, anticoagulation and Ca-antagonists were routinely applied after treatment. Multiple studies with medical intervention have been performed, mostly with anticoagulants. However, no effective reduction of restenosis has been achieved so far. Analysis of autopsy tissue obtained after angioplasty indicated the importance of early vascular wall "response to injury" that might as a consequence lead to restenosis formation. This was confirmed by systematic experimental data. With introduction of directional atherectomy "biopsies" of primary and restenotic tissue were obtained. Thus, a subtile diagnostic spectrum including histological, immunohistochemical, electron microscopical, and molecular tissue analysis could be established. In vitro cultures of obtained tissue were performed routinely. They enable a characterization of proliferative and synthetic cellular features. Moreover, the effects of therapeutic measures can be quantified and used for pre-clinical screening. To date, the above described methods indicate as pivotal event the angioplasty induced transformation of contractile myocytes to a synthesizing type of myocytes. The transformation to synthetic active cells is not device dependent, but seems to be a major feature of restenosis. This process is mostly terminated in a period of 3-6 months. To accelerate this physiologic termination would be one interesting therapeutic option. Alternatively, special local drug delivery devices could be used to administer sufficient antiproliferative drugs at the site that needs to be treated.

Angioplasty, Balloon, Coronary↗

PubMed1994

New morphologic aspects of explanted Hancock Extracorporeal pericardial bioprostheses.

Between 1981 and 1987 a total of 479 Hancock Extracorporeal bovine pericardial bioprostheses were implanted in 458 patients. During the time period from 1990 to 1993, 21 valves, 15 in the aortic and six in the mitral position, had to be removed 72 to 109 months after implantation. The mean age of these patients at the time of implantation was 49.7 +/- 10.5 years. All 21 removed as well as one unimplanted bioprosthesis were morphologically investigated. Visual examination, radiography, histology and ultrastructural observations were performed using scanning and transmission electron microscopy. In addition, clinical data were correlated to morphological findings. All valves failed due to cusp tears originating at the stent posts. Calcification was minimal in five valves, moderate in 10, and severe in five valves. Only one valve showed no mineralization at all. The late morphologic changes were associated with thickening of valve leaflets, tissue delamination, calcification, degeneration of collageneous network, and extensive insudation of plasma proteins and lipids. The present findings suggest that denatured collagen molecules may be capable of inducing immune response.

Adult↗

PubMed1993

Analysis of atherectomy specimens.

Atherectomy specimens may be regarded as biopsy tissue excised from human vascular target lesions. Proceeding from contrary histologic findings that attribute focal hypercellularity to restenosis, and hypocellularity to chronic lesions, further analysis of atherectomy specimens was performed to study ultrastructural characteristics and functional aspects propagated by both lesion types. Transmission electron microscopy examination showed that intimal smooth muscle cells (SMCs) were the predominant cells in both primary and restenotic lesions. SMCs exhibited variable degrees of metabolic activation, typically higher in SMCs of restenotic lesions. This SMC phenotype was equally expressed when tissue samples were placed in a cell culture model. In an attempt to quantify SMC activity, proliferative as well as migratory activities of cultured cells were measured by growth curves and a computer-assisted motion analysis system, respectively. A 2- to 3-fold increase of both activity determinants was observed with SMCs cultivated from restenotic lesions compared with those from primary lesions, irrespective of their coronary or peripheral origin. Drug-induced interference of human SMC metabolic activation and antagonism to their proliferative and migratory activities may be helpful in evaluation of therapeutic concepts to prevent restenosis. The antitubulin colchicine was studied for its effect on the defined determinants. The data in vitro demonstrate that colchicine decreased proliferative and migratory activity of SMCs and caused disorganization of the cytoplasmic ultrastructure. In conclusion, electron microscopy and cell culture studies may help to shed more light on the structures and mechanisms underlying restenosis and plaque growth. Deliberate counteraction of any of the specific early events implicated in these complex pathobiologic processes may eventually become effective means to suppress restenosis and may thus result in a prophylactic as well as therapeutic treatment of the diseased vascular wall.

Animals↗

PubMed1993

Results of directional peripheral atherectomy with reference to histology, histochemistry, and ultrastructure.

One hundred patients with symptomatic peripheral vascular disease were treated with a directional atherectomy catheter; 153 lesions comprising 98 stenoses and 55 occlusions were located in the iliac (n = 22), superficial femoral (n = 114), popliteal (n = 16), and anterior tibial (n = 1) arteries. The majority of these patients were poor candidates for balloon angioplasty because of the complexity of lesions. There were 70 eccentric and 28 concentric lesions and 55 occlusions (mean length 4.2 +/- 2.9 cm). Acute success rate was 94% for both stenoses and occlusions. Four patients were treated in both lower extremities. The stenoses were reduced from 85 +/- 12% to 12 +/- 10% acutely (occlusions 100% to 9 +/- 9%). Six-month angiographic follow-ups were performed in 81% of treated patients, the others refusing angiography. Mean stenosis after six months was 33 +/- 25% (occlusions 44 +/- 28%). Restenosis (> 50%) was found in 20% of treated lesions: 26% in concentric lesions, 8% in eccentric lesions, and 32% in occluded vessels. Treatment of peripheral vascular disease with the atherectomy device is safe and effective therapy with good long-term results. These results were obtained in complex lesions with 55 occlusions. Atherectomy seems to be particularly beneficial in the treatment of eccentric and complex stenoses and is not limited by occlusion or calcification. Furthermore, insight into the pathogenesis of arteriosclerosis and the development of restenosis is enabled by analysis of removed plaque material.

Aged↗