[Increased expression of growth factors following angioplasty. Restenosis by stimulation of vascular smooth muscle cells].
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Biomedical subjects
Publications and source records attributed to G Bauriedel.
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Symptomatic patients with total superficial femoral artery occlusions were approached with a modified Dotter technique followed by PTA and/or atherectomy. In 21 lesions studied, 7 (33%) were crossed with a conventional guide wire. Of the remaining 14 lesions (67%), 12/14 (86%) were crossed successfully using the pliable distal tip of the sheath introducer. The average angiographic lesion length crossed was 42 +/- 29 mm (range 8-109 mm). One insertion site vessel complication requiring surgical repair was seen. Although more advanced technologies have been developed to treat "wire resistant" total occlusions, the use of the introducer technique described is effective in many patients and adds no additional cost or time to the standard angioplasty procedure.
Directional coronary atherectomy (DCA) was used in 10 female and 50 male patients with an average age of 58 years. They were categorized into three different groups depending on the indications for atherectomy. Group 1 included all patients who had atherectomy as their primary intervention (n = 20) because they were assumed to be unsuitable for percutaneous transluminal coronary angioplasty (PTCA). Group 2 consisted of patients in whom DCA was used after failed balloon dilatation with unsuccessful but uneventful treatment (n = 17). Group 3 (n = 23) included patients in whom DCA was performed as a "rescue" or "bailout" procedure after unsuccessful PTCA resulting in critical ischemia (ECG changes, chest pain, hypotension, and shock). The target lesions were located in the left main artery in two, left anterior descending artery in 43, right coronary artery in 15, and aortocoronary venous bypass in five. The mean length of the lesions was 8 mm (2 to 25 mm). The overall success rate for 65 lesions was 92%. The mean stenosis was reduced from 87 +/- 12% to 19 +/- 17% in patients with primary success. Presently available follow-up angiograms (30) showed six restenoses. Major complications occurred in seven patients (myocardial infarction in two and coronary artery bypass graft surgery within 24 hours in five); there were no deaths. Our results show that DCA is a safe and effective technique that can extend the use of percutaneous procedures and provide a promising nonsurgical option in cases of unsuccessful PTCA.
BACKGROUND: The successful cultivation of human smooth muscle cells (SMC) from coronary and peripheral atherosclerotic lesions removed by percutaneous directional atherectomy is described. METHODS AND RESULTS: Sixty-seven patients in whom plaque material was obtained compose the study population. A total of 73 lesions from both coronary (n = 38) and peripheral (n = 35) arteries of primary (n = 50) and restenotic origin (n = 23) were studied. Successful cultivation was significantly (p less than 0.001) dependent on the quantity of plaque material submitted. Fifty-five percent of patients in whom atherectomy specimens were removed from coronary lesions yielded an adequate SMC population in comparison to 89% of those from peripheral arteries (p less than 0.01). Cultivation was not dependent on the age and sex of patients, lesion origin, risk factors, medications, or incidence of unstable angina. In an attempt to quantify SMC activity, migratory velocity was measured with a computer-assisted motion analysis system. SMC migratory velocity was found to be significantly (p less than 0.001) greater in restenotic than in primary plaque material. This finding was confirmed for both coronary and peripheral lesions. CONCLUSIONS: Our data suggest that elevated SMC migratory activity may be an important mechanism in the development of restenotic lesions.
Growth factors and growth factor receptors are considered to be key elements in the pathogenesis of arteriosclerosis and restenosis formation. To study the local expression of epidermal growth factor (EGF) receptor, plaque tissue specimens from advanced lesions (10 coronary, two femoral, seven carotid) of 19 patients were taken for in situ hybridization studies using an EGF-specific cDNA probe. In serial vascular sections of three lesions with increased focal cellularity, autoradiographic silver grains were clearly localized to intimal cells adjacent to the internal elastic lamina. EGF mRNA transcripts were not observed in the fibrous cap, the plaque shoulders, necrotic intimal areas, or in the media. In smooth muscle cells (SMCs) cultured from human plaque tissue, EGF increased SMC proliferative activity in a dose-dependent manner (ED50: 3-6 ng of EGF/ml). Proliferative responsiveness to EGF (10 ng/ml) was found to be significantly (p < 0.01) enhanced in coronary SMCs derived from restenotic lesions as compared to those from primary stenoses. The expression of EGF receptor mRNA in human atheromatous lesions could be of prognostic value to predict an increased SMC proliferative response to stimulatory growth factors.
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Proliferative, migratory, and secretory activities of vascular smooth muscle cells are currently discussed as determinants of human plaque and restenosis formation. Affecting these determinants with drugs may promise anti-arteriosclerotic effects. Plaque tissue was removed from both coronary and peripheral lesions of a total of 18 patients to cultivate smooth muscle cells (SMC) for subsequent in vitro studies. The antitubulin colchicine (C) caused a concentration-dependent decrease of SMC proliferative activity with an IC50 of 5 x 10(-9) M. Migratory activity was analyzed by a standardized semi-automatic video system. This parameter was reduced by C in a concentration-dependent manner (IC50: 5 x 10(-10) M). As shown by immunofluorescence microscopy, the typical structure of microtubules of C-treated SMCs was distorted, whereas the pattern of alpha-actin filaments remained unaltered. Transmission electron microscopy (TEM) revealed that the number of microtubules was diminished after addition of C, and that a distinct disorganization of cytoplasmic organelles as well as the formation of vacuoles had occurred. In vitro studies of human smooth muscle cells derived from vascular plaques indicate that colchicine may be useful as an anti-arteriosclerotic drug, since a concentration-dependent concordant effect on proliferation, migration, and secretory processes of the SMC could be demonstrated.
130 arteriosclerotic lesions--10 in the iliac, 109 in the superficial femoral, 10 in the popliteal and 1 in the anterior tibial artery--were treated by percutaneous atherectomy in 80 patients (62 men and 18 women: mean age 65 +/- 10 years). 23 of the lesions were concentric, 65 eccentric stenoses, while 42 were fully occlusive. 32 patients were in stage IIb (after Fontaine), 24 in stage IIa and 12 each in stage III or IV. Most of the stenoses were not suitable for conventional balloon dilatation because of their primary morphology. A good early angiographic result (residual stenosis less than 50%) was achieved in 94% of lesions. Mean stenosis degree was reduced from 85 +/- 12% to 12 +/- 10% (occlusions from 100% to 9 +/- 9%). The Doppler index increased from 0.6 +/- 0.18 to 0.85 +/- 0.15 (P less than 0.01). Follow-up angiography after 6 months in 104 lesions demonstrated an average stenosis degree of 33 +/- 25% (occlusions 44 +/- 28%). 26 of the 104 re-studied lesions fulfilled the criterion for re-stenosis (greater than 50%): six concentric ones and five eccentric ones, as well as 15 occlusions. These findings indicate that peripheral atherectomy can be employed with good short and long-term results even in morphologically unfavourable, markedly eccentric or calcified lesions and occlusions.
The role of adjunctive video angioscopy was evaluated in 43 patients with symptomatic peripheral vascular disease undergoing percutaneous atherectomy with the Simpson atherocath. There were 57 target lesions (superficial femoral, n = 46; popliteal, n = 11) of which 33 were stenotic (86 +/- 11%) and 24 were total occlusions of 0.5 to 10.6 cm in length, determined by angiography. Intraluminal inspection, with angioscopes of 0.85 to 1.5 mm in outer diameter housed within a guide catheter, could be performed in 55 of 57 lesions (96%) before atherectomy and in 39 of these 55 (71%) after atherectomy. Failure to obtain an adequate image was usually due to insufficient irrigation, especially in recanalized vessels. In 13 of 23 successfully recanalized arteries (54%) the occlusion could be crossed by the angioscope itself, whereas in 10 cases (42%) a guidewire or a sheath introducer was necessary. Angioscopic passage revealed that often long total occlusions, determined by angiography, consisted of greater than or equal to 1 discrete occlusion with interposed patent thrombus-free vascular segments. After atherectomy, in 15 instances with an acceptable angiographic result, angioscopy was helpful in identifying residual plaques and flaps which then selectively underwent atherectomy. In conclusion, angioscopy proved to be a useful adjunct to angiography in optimizing vascular recanalization with percutaneous atherectomy.
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Besides proliferation, migration of smooth muscle cells (SMC) is considered to be an essential cellular mechanism involved in plaque formation. Human SMCs were cultured from 14 arteriosclerotic lesions of coronary (n = 5), femoral (n = 7) and aortic (n = 2) arteries. By a semi-automatic standardized video analysis system SMC migratory activity was quantified to be 21.7 +/- 2.1 microns/h (n = 14; x +/- SD). Addition of drugs, such as calcium antagonists (10(-5) - 10(-7) M), heparin (100 micrograms/ml), SIN-1 (10(-5) M) and colchicine (10(-7) M) resulted in a significant decrease of SMC migratory velocity. Exposure to endogenous extracellular matrix proteins (5 micrograms/cm2) showed no effect for collagen I and a significant reduction of SMC migratory activity for fibronectin, respectively. Our results indicate SMC migratory velocity to be a parameter of potential interest to screen various substances for an anti-arteriosclerotic effect.
Directional coronary atherectomy (DCA) was used in 74 patients with an average age of 56 years. They were categorized into three different groups depending on the indications for atherectomy. Group I included all patients who had atherectomy as their primary intervention (n = 26), because they were assumed to be unsuitable for PTCA. Group II consisted of patients in whom DCA was used after failed balloon dilatation with unsuccessful but uneventful treatment (n = 20). Group III (n = 28) included cases where DCA was performed as a "rescue" or "bail-out" procedure after failed PTCA resulted in critical ischemia (ECG changes, chest pain, hypotension, and shock). The target lesions were located in LM 2, LAD 52, RCA 16, ACVB 4. The mean length of lesion was 8 mm (2-25 mm). The overall success rate was 94%. The mean stenosis was reduced from 90.6 +/- 10% to 17.2 +/- 14.8% in cases with primary success. The presently available follow-up angiography (n = 31) showed six restenoses. Major complications occurred in seven cases (death: 0, myocardial infarction: 2, CABG within 24 h: 5). Histological analysis revealed highly cellular areal as a major characteristics of a coronary lesion and also of restenotic tissue. Tissue of the lamina elastica was present in 44% and of media in 14%. Thrombus was found only rarely. Ultrastructure showed a significant amount of extracellular matrix in the primary coronary lesions and isolated smooth muscle cells without gap-junctions. RER, mitochondria were typical for the synthesizing type of smooth muscle cell. In restenotic tissue a focal high density of smooth muscle cells with increased synthesizing activity and gap-junctions was present. Endothelial cells (and macrophages) were found only rarely. Furthermore, altered smooth muscle cells from restenotic tissue showed a significantly increased migration and proliferation. Our results show that DCA is a safe and effective technique that can extend the use of percutaneous procedures and provide a promising, nonsurgical option in cases of failed PTCA. Histological analysis revealed a proliferative process as a characteristics of restenosis development.
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We used directional coronary atherectomy (DCA) as a therapeutic option for coronary lesions unsuitable for PTCA (eccentric, ostial, branching or restenotic) and as "rescue device" for failed PTCA. Forty-two patients were treated by DCA using the Simpson coronary atherectomy device, including four female and 38 male patients with an average age of 55.7 years. Atherectomy as primary intervention was performed in 16 patients (Group I), because morphology of their lesions was assumed to be unsuitable for PTCA. DCA was also used after failed balloon dilatation in eight patients with unsuccessful, but uneventful treatment (Group II). In 18 cases (Group III) DCA was performed as "rescue procedure" after failed PTCA and resulting critical ischemia (local dissection, signs and symptoms of ongoing ischemia, occlusion after PTCA). Target lesions were located in LM 1, LAD 33, RCA 9, CABG 3. Mean length of lesion was 8.1 mm (2-25 mm). The overall success rate for 46 lesions was 93%. Mean stenosis was reduced from 92% to 17% in cases with primary success. Presently, available follow-up angiography (24) showed six restenoses (defined as greater than 50% stenoses). Major complications occurred in seven cases (death: 0, MI: 2, CABG within 24 h: 5; 3 in Group III). "Rescue indication" (Group III) after failed balloon dilatation procedure showed a favorable primary result with a success rate of 78%; only three cases of this group needed CABG. Our results show that DCA is a safe and effective technique which can extend the indication for percutaneous procedures and gives a successful nonoperative option in cases of failed PTCA.