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G Bauriedel

Publications and source records attributed to G Bauriedel.

At least 37 records · Page 2Linked to original sources
PubMed2002

[Micro-coil embolization of a fistula of the circumflex ramus in the coronary sinus. Case report, differential therapy and review of the literature].

A 45 year old male suffered from typical exercise-induced dyspnoea and angina. Crohn's disease treated with glucocorticoids was present for 18 years. Coronary angiography revealed small left anterior descending and right coronary arteries without reference to coronary artery disease, while the main stem and circumflex artery were severely dilated due to a fistula (diameter 5.5 mm) into the coronary sinus with a left/right shunt amounting to 35%. Haemodynamics, significant risk of endocarditis with chronic inflammatory bowel disease and obligatory glucocorticoid treatment were indications for fistula closure. As an alternative to surgical correction, the coronary fistula was totally occluded by antegrade micro-coil embolization. The present report offers a review on differential therapeutic considerations and specific treatment options including novel interventional modalities for coronary fistulas.

Arteriovenous Fistula↗
PubMed2002

[Chlamydia pneumoniae and cytomegalovirus in degenerative aortic valve stenoses].

Recent evidence suggests a causal relationship between inflammatory as well as infectious pathomechanisms and valvular degeneration. Based on the concept of chronic Chlamydia pneumoniae and cytomegalovirus (CMV) infections, and of variable stressors working on valvular microecology, the present study sought to assess the presence of the specific chlamydial heat shock protein (cHSP) 60, of CMV, of macrophages and of the human homologue hHSP60. Serial sections of high-grade degenerated native (n = 16) and prosthetic (n = 6) aortic valves were analyzed by immunohistochemistry for the presence of these determinants. Degenerated aortic valves revealed prevalence of Chlamydia pneumoniae in 41% (10 of 22) and CMV in 73% (16 of 22), while immunoreactive hHSP60 was present in 64% (14 of 22) and CD68 in 86% (19 of 22). Chlamydial HSP60, CMV and hHSP60 were predominantly found in valvular fibrosa; CMV showed a second predilection site at the ventricular luminal border. Both microorganisms revealed a strong correlation between each other (r = 0.73; p < 0.001) as well as with hHSP60 (cHSP60: r = 0.74; p < 0.001; CMV: r = 0.80; p < 0.001). Macrophage infiltration correlated with cHSP60 (r = 0.78; r < 0.001), CMV (r = 0.78; r < 0.001) and hHSP60 (r = 0.56; r = 0.007). Of note, the frequency of cHSP60, CMV and CD68 signaling was increased more than 5-fold in prosthetic valves compared to native valves (p = 0.017, p = 0.002 and p = 0.005). In summary, valvular infections of Chlamydia pneumoniae and of cytomegalovirus are frequently seen in degenerated aortic valves, irrespective of native or prosthetic origin. Colocalization of both HSP60 homologues and cytomegalovirus within macrophages in valvular fibrosa points to regional stressor effects that might be at least partly attributable to chronic persistent pathogen burden and molecular mimicry.

Aged↗
PubMed2001

[QT prolongation and torsade de pointes tachycardia during therapy with maprotiline. Differential diagnostic and therapeutic aspects].

HISTORY AND ADMISSION FINDINGS: A 69-year-old somnolent woman developed severe heart failure, aggravated by recurrent episodes of ventricular tachycardia. The patient showed central and peripheral edema. 24 hours earlier, she had suffered cerebral seizures that were successfully terminated by phenytoin. For 13 years, persistent atrial fibrillation had been frequency-controlled with antiarrhythmic drugs (verapamil and glycosides) and treated by oral anticoagulation. In addition, there had been long-term anti-depressant therapy with the tetracyclic agent maprotiline. INVESTIGATIONS: Torsade de pointes tachycardia was documented in the electrocardiograms. In addition, the QT interval was extensively prolonged (QTc = 0.70 sec). Neither electrolyte disturbances nor acute cardiac ischemia were seen. Echocardiography revealed a highly reduced ejection fraction of 25 % and a moderately dilated left ventricle. Angiography showed a collateralized occlusion of the right and plaques of the left coronary artery. TREATMENT AND COURSE: Repeated torsade de pointes tachycardia resulted in hemodynamic compromise and were terminated by defibrillations. After intravenous magnesium and xylocaine administration as well as with termination of maprotiline and antiarrhythmic co-medication, QT prolongation decreased. In addition, the recurrent torsade de pointes tachycardia stopped. Subsequently, however, there were several bradycardia episodes, QT duration remained long. Accordingly, a VVI pacemaker was implanted. Up to now, the patient is doing well. CONCLUSIONS: With antidepressant therapy, a risky constellation including comorbidity and interactions with potentially arrhythmogenic drugs may lead to QT prolongation. Medication that delays conduction or causes bradycardia may generally favour torsade de pointes tachycardia. In case of indispensable multi-drug therapy, regular clinical as well as electrocardiographic monitoring with special emphasis on QT interval is mandatory.

Aged↗
PubMed2001

[Epstein-Barr virus-associated pericarditis].

HISTORY AND ADMISSION FINDINGS: A 73 year old woman presented with increasing dyspnoea caused by a large pericardial effusion. INVESTIGATIONS: Transthoracic echocardiography revealed a diastolically 35 mm broad pericardial effusion. Subxiphoidal drainage controlled by ultrasound delivered 350 ml of a haemorrhagic fluid that was submitted to pathology and microbiology examination. This was completed by serological and immunological tests and a specific extensive search for malignant diseases, i. e. computer tomograms of chest and abdomen, mammography, bronchoscopy, gastroscopy and coloscopy. All examinations were negative. However, nested PCR analysis of blood leucocytes and of pericardial effusion revealed the pericardial presence of Epstein-Barr virus (EBV), consistent with a localized pericardial EBV persistence or reactivation. TREATMENT AND COURSE: Follow-up showed a complete resolution of the pericardial effusion without the necessity of further specific treatment. CONCLUSIONS: Although EBV infection is common in the general population, cardiac involvement, in particular in the adult, is infrequent and usually takes an uncomplicated course. The present case report demonstrates a beginning pericardial tamponade due to localized pericardial EBV persistence or reactivation without detectable systemic EBV infection. In addition, the importance of molecular tests for diagnostic accuracy is highlighted.

Aged↗
PubMed2001

[Decreased platelet aggregation during angiotensin-converting enzyme inhibitor therapy. Results of a pilot study].

BACKGROUND AND OBJECTIVE: Plaque rupture and subsequent thrombosis are key events in the complication and progression of atherosclerotic disease. Recently, the HOPE study showed a significant decrease in cardiovascular complications with the angiotensin converting enzyme (ACE) inhibitor (ramipril). To assess the therapeutic potential of this drug class, the present study evaluates the coagulative activity in cardiovascular patients with ACE inhibitors and compares these data with those of untreated patients and with those of patients taking aspirin, resp. METHODS: Blood samples from 204 patients with coronary heart disease and/or arterial hypertension were analyzed by whole-blood lumi-aggregometry. Platelet aggregation was determined by the increase in impedance across paired electrodes in response to the stimulatory agents collagen and ADP, respectively. The data were correlated with the presence or absence of ACE inhibitor and/or aspirin medication. Analogously, the coagulative potential of beta-blockers, calcium antagonists, CSE-inhibitors and nitrates were studied. RESULTS: As the central finding, study participants treated with ACE inhibitors showed a decreased platelet aggregation compared to untreated control patients, indicated by a significantly reduced increase in impedance. Platelet aggregation induced by collagen decreased by 18% (p = 0.025), that induced by ADP by 39% (p = 0.039). With aspirin medication, the collagen-induced decrease amounted to 20% (p = 0.020); no significant effect was seen by ADP stimulation. With combined intake of ACE inhibitors and aspirin, collagen-induced platelet aggregation was found markedly reduced. Platelet aggregation decreased by 26% (p = 0.003). Beta-blockers, calcium antagonists, CSE inhibitors and nitrates did not reveal a significant influence on platelet aggregation. CONCLUSIONS: ACE inhibition decreases platelet aggregation, as detected and quantified by ex vivo whole-blood aggregometry. Beyond known effects of this drug class, in particular on endothelium and fibrinolysis, antithrombotic effects may explain the positive influence on major clinical cardiovascular events.

Aged↗
PubMed2001

Selection and characterization of active hammerhead ribozymes targeted against cyclin E and E2F1 full-length mRNA.

Proliferation of vascular smooth muscle cells is generally accepted as a key event in the development of restenosis following percutaneous transluminal angioplasty. To prevent human restenosis, we have designed a molecular strategy based on hammerhead ribozymes targeted against the mRNA of cyclin E and E2F1, two proteins relevant in cell cycle progression whose regulation is interconnected by a positive feedback loop. Following the identification of accessible ribozyme target sites by RNase H mapping, several hammerhead ribozymes were generated that cleave with comparable efficiency two different splice forms of cyclin E mRNA and the full-length and a truncated form of E2F1 RNA, respectively. The most active ribozymes were tested in vitro under single-turnover conditions yielding k(react)/K(m) ratios between 36 and 73 x 10(4) M(-1) min(-1), which places them in the top range ribozymes targeted against long and structured substrates. In addition, we show that the most active ribozyme selected in vitro reduces specifically and significantly (p < 0.0028) proliferation of cultured human vascular smooth muscle cells (VSMC).

Base Sequence↗
PubMed2000

[Penetrating atherosclerotic ulcer of the thoracic aorta descendens]

Penetrating atherosclerotic ulcer of the thoracic aorta descendens. HISTORY AND CLINICAL FINDINGS: A 75-year-old man with a history of generalised atherosclerosis was admitted to hospital for invasive assessment of progredient typical angina pectoris. Apart from diminished peripheral pulses, physical examination was normal. INVESTIGATIONS: Coronary angiography revealed a three vessel coronary artery disease. The chest X-ray showed elongation and dilatation of the distal aortic arch and the proximal descending aorta thoracalis. Computed tomography and magnetic resonance imaging of the thorax as well as magnetic resonance angiography of the thoracic aorta, demonstrated a penetrating atherosclerotic ulcer of the descending aorta thoracalis, with extensive intramural hematoma. TREATMENT AND COURSE: After percutaneous ballon-dilatation of the right coronary artery and the circumflex artery, the patient was asymptomatic. Considering all aspects of the patients condition, medical treatment of the penetrating atherosclerotic ulcer was decided for the patient. The findings of the thoracic computed tomography after 6 months were unchanged. CONCLUSION: The penetrating atherosclerotic ulcer of the thoracic aorta is a less known clinical entity. Our case report demonstrates that even extensive forms can be clinical asymptomatic and discovered by routine radiologic examinations.

Journal Article↗
PubMed2000

[Ventricular septal defect following cardiac trauma: closure with the Amplatzer Septal Occluder]

Ventricular septal defect following cardiac trauma: percutaneous closure with the Amplatzer septal occluder. HISTORY AND CLINICAL FINDINGS: A 36-year old roofer fell 8 m and suffered a severe polytrauma. A complicating pericardial tamponade was relieved as an emergency and myocardial fissure of the left ventricle about 1 cm in length sutured. 2 weeks later, a severe mitral insufficiency due to rupture of the papillary muscle occurred, that was cared by the implantation of a bioprosthesis. 6 weeks later dyspnoea and restricted physical capability were clinically impressive. INVESTIGATIONS AND DIAGNOSIS: Echocardiography demonstrated a posttraumatic muscular ventricular septal defect. Doppler echocardiography and heart catheterization showed a ventricular septal defect still restrictive with a left-to-right shunt (pulmonary-to-systemic flow ratio Qp/Qs 1.8:1). Under exercise, there was a significant increase in mean pulmonary arterial pressure from 27 to 60 mmHg. TREATMENT AND COURSE: The patient who had already been operated twice before was treated by the percutaneous occlusion of the ventricular septal defect from arterio- to venofemoral, a guide catheter was inserted transseptally into the left ventricle. An Amplatzer Septal Occluder, a self-expandable, self-centering wire-mesh double disc with a connecting central stent part, was loaded and then implanted in the ventricular septal defect. The intervention was controlled by fluoroscopy and echocardiography. Post intervention, only a trivial residual shunt was seen. The pumping efficacy of the left ventricle increased, in particular of the septal and apical segments. Clinically, the patient was markedly more load-bearing, the exercise-induced dyspnoea reduced. CONCLUSIONS: Following a cardiac trauma, various complications may occur that can manifest themselves clinically at two or more times. A posttraumatic ventricular septal defect of a patient already operated was successfully occluded by an Amplatzer Septal Occluder. Alongside established surgical methods, the non-operative implantation of new occlusion systems could mean an effective treatment option for muscular ventricular septal defects.

Journal Article↗
PubMed1999

[Persistence of Chlamydia pneumoniae in coronary plaque tissue. A contribution to infection and immune hypothesis in unstable angina pectoris].

BACKGROUND AND OBJECTIVE: There is an increasing number of pointers towards a causative connection between Chlamydia pneumoniae and atherosclerosis. But the pathogenetic mechanism and intimal structures that are involved remain unclear. Starting with the hypothesis of a chronic infection, as demonstrated by the presence of the chlamydial stress (heat-shock) protein 60 (HSP 60), the presence and localization of these bacterial products in coronary atheromas was investigated. PATIENTS AND METHODS: Coronary atheroma tissue from primary stenoses in 42 patients (36 men, 6 women, mean age 60.2 +/- 7.3 years) was studied immunohistochemically in the course of a retrospective analysis for chlamydial HSP 60. The findings in clinically acute coronary syndrome (Braunwald's classification) present in 27 patients were compared with those in 15 patients with acute angina and evaluated in relation to expression and site of predilection. RESULTS: An immune reaction to chlamydial HSP 60 was demonstrated in 27 of 42 atheromas (64%). Intact, non-atherosclerotic vessels, such as the mammary artery and sphenous vein, showed no such signals. Chlamydial HSP 60 was localized in maximally 23% of all plaque cells, mostly in macrophages/foam cells, more rarely in smooth muscle cells. Chlamydia in foam cells most often revealed ultrastructural patterns that pointed to the persistence of the pathogen. Sites of predilection of chlamydial HSP were predominantly foam cell areas and cell-poor regions, more rarely inflammatory infiltrates and areas of rupture. When comparing both types of lesion, signals for chlamydial HSP 60 were present in 21 of the 27 atheromas (78%) with unstable angina or acute myocardial infarction, but in only 6 of the 15 atheromas (40%) with stable angina. Within the group with the acute coronary syndrome, the prevalence of chronic chlamydial infection was independent of a previous myocardial infarction. CONCLUSIONS: Chlamydial HSP 60 can often be demonstrated in primary coronary stenosis of symptomatic patients. It is most frequently found in macrophages/foam cells and is highly prevalent in the acute coronary syndrome. In-situ findings suggest a pathogenetically relevant role of chronic persistent infection of Chlamydia pneumoniae in unstable coronary plaques.

Adult↗
PubMed1999

[Chlamydia pneumoniae in coronary plaques: Increased detection with acute coronary syndrome].

BACKGROUND AND OBJECTIVE: There is seroepidemiologic and experimental evidence for a link between Chlamydia (C.) pneumoniae and arteriosclerosis. However, the clinical importance and the pathogenic pathways implicated remain unclear. In the present study, we sought to evaluate the presence and the location of C. pneumoniae in coronary atheroma, as well as a potential prevalence with unstable versus stable angina. PATIENTS AND METHODS: Retrospectively, coronary plaque material of primary lesions from 51 consecutive patients (44 men, 7 women, mean age 59.6 +/- 9.4 years) was examined for the presence of C. pneumoniae by use of immuno-histochemistry and transmission electron microscopy. The findings associated with clinically acute coronary syndrome according to Braunwald's classification (n = 31) were compared to those with stable angina (n = 20) and regarded for potential relations to characteristic intimal features. RESULTS: Immunoreaction for C. pneumoniae was found in 32 of 51 (63%) coronary plaques. Signals (% prevalence of specific intimal features) were present with necrotic areas (40%), sparse cellularity (40%), neo-vascularization (29%), thrombi (20%), ruptured plaque areas (19%), and fields rich in foam cells and calcifications (13%). Intimal hyperplasia and inflammatory infiltrates showed no signals. As the central finding in this report, C. pneumoniae immunoreaction was more frequently (P < 0.001) found in 26 of 31 (84%) lesions associated with unstable angina or acute myocardial infarction, compared to 6 of 20 (30%) lesions with stable angina (P < 0.001). Intact vessels devoid of arteriosclerotic disease, such as mammarial arteries and saphenous veins, were without C. pneumoniae signals (negative controls). Ultrastructurally, chlamydial elementary bodies were found in foam cells and phagocytosing macrophages, also in fragmented extracellular matrix adjacent to apoptotic and necrotic intimal cells. CONCLUSIONS: Chlamydiae pneumoniae were detected in 32 of 51 (63%) coronary primary lesions of symptomatic patients. Most importantly, there was a highly significant prevalence of lesions associated with acute coronary syndrome. Predilection sites of C. pneumoniae were areas that revealed small healing activity and (or) propensity to plaque rupture. The present in situ findings indicate a pathogenic role of Chlamydiae pneumoniae in human (coronary) plaque rupture.

Aged↗
PubMed1999

[Congenital cardiovascular malformations and chromosome microdeletions in 22q11.2].

BACKGROUND AND OBJECTIVE: Congenital cardiovascular (c-v) malformations are the leading signs of two syndromes of highly variable phenotypes, the DiGeorge syndrome (DGS) and the velo-cardio-facial syndrome (VCFS), both of which in the majority of cases are caused by microdeletion in the chromosome region 22q11.2. It was the aim of this study to ascertain the frequency of these chromosomal abnormalities in patients with unselected congenital cardiovascular malformation, and to assess the type of c-v malformation for which microdeletion analysis of the mentioned region would be indicated. PATIENTS AND METHODS: The cohort consisted of 90 patients with congenital c-v malformations (35 males, 55 females; mean age 3.6 years (19th week of pregnancy-36 years). Most of them were newborns. The c-v anomalies were: ventricular septal defect (n = 20), pulmonary atresia (10), Fallot's tetralogy (9), truncus arteriosus communis (6), aortic valve stenosis (6), atrioventricular canal (6), type B interrupted aortic arch (5), atrial septal defect (5), tricuspid atresia (4), hypoplastic left heart syndrome (4), persisting ductus arteriosus (3), pulmonary valve stenosis (3), complete (third degree) atrioventricular block (2), Ebstein's anomaly (1), tachycardia (1) and enlarged right atrium (1). Four of 14 fetuses included in this study had complex cardiac anomalies that could not be definitively classified. Cytogenetic karyotype analysis was unremarkable in all cases. Microdeletion detection was done by fluorescence-in-situ-hybridization (FISH). RESULTS: 14 of the 90 cases (about 16%) showed microdeletion in the examined chromosomal region 22q11.2. Among the group with microdeletion were aortic arch interruption (5/5), ventricular septal defect (2/20). Fallot's tetralogy (1/9) and atrial septal defect (1/5). All the deletion carriers had other signs of the DGS/VCFS complex. One parent each in two of the microdeletion patients had the same microdeletions. CONCLUSION: In patients with congenital c-v and associated malformations of dysmorphism microdeletion diagnosis of 22q11.2 by FISH is indicated in addition to conventional cytogenetic testing. The incidence of this microdeletion seems to be especially high among patients with type B interrupted aortic arch.

Adolescent↗
PubMed1999

Role of smooth muscle cell death in advanced coronary primary lesions: implications for plaque instability.

OBJECTIVE: Instability of coronary atheroma leads to the onset of acute coronary syndromes including myocardial infarction and death, as well as to the progression of the arteriosclerotic disease. As yet, the underlying factors and mechanisms causing plaque rupture are not completely understood. Since a low content of smooth muscle cells (SMCs) apparently plays a key role, the question points to the events leading to the loss of intimal SMCs. METHODS: We compared coronary atherectomy specimens from 25 patients with unstable angina to those from 25 patients with stable angina. Transmission electron microscopy was used to identify intimal cell population, to detect stage and cell type of apoptosis, and to differentiate between apoptosis and necrosis. RESULTS: Plaques associated with unstable angina contained more macrophages/lymphocytes and significantly less SMCs (P = 0.01), compared with stable angina plaques. Specific cell death forms, apoptosis and necrosis, were present in all coronary atheroma. As key findings, both the proportion of SMCs undergoing apoptosis and the frequency of cytoplasmic remnants of apoptotic SMCs (matrix vesicles) were significantly increased in unstable versus stable angina lesions (P = 0.002 and P = 0.002). In addition, cellular necrosis was more frequent in the first coronary atheroma group (P = 0.02). Positive correlations were found between the frequency of apoptotic cells and necrosis (r = 0.41, P = 0.04), and that of matrix vesicles and necrosis (r = 0.63, P = 0.001) only in plaques with unstable angina, but not in those with stable angina. CONCLUSIONS: Our data demonstrate that high cell death due to apoptosis and necrosis is a basic in situ feature found in advanced coronary primary lesions associated with unstable angina, possibly explaining their low density of (viable) SMCs. Thus, antagonization of intimal cell death should be considered in order to stabilize the intimal plaque texture of coronary atheroma with the ultimate goal to prevent plaque rupture.

Adult↗
PubMed1998

Apoptosis in restenosis versus stable-angina atherosclerosis: implications for the pathogenesis of restenosis.

Decreases in programmed cell death (apoptosis) may contribute to restenotic hyperplasia by prolonging the life span of intimal cells. Apoptotic events were compared in restenotic versus primary lesions, by using atherectomy samples from 16 restenotic and 30 primary human peripheral and coronary lesions from patients presenting with stable angina. We used transmission electron microscopy to identify apoptosis, quantify its frequency, distinguish apoptosis from necrosis, and relate these events to cellular composition. Smooth muscle cell (SMC) density was higher in restenotic versus primary lesions (P<0.0001), whereas the number of macrophages was significantly reduced (P<0.01) and the number of lymphocytes was lower, but not significantly (P=0.06). As the main finding, restenotic lesions contained fewer apoptotic cells compared with primary lesions (3% versus 13%, P=0.002), whereas no differences were found for cellular necrosis. With regard to cell type, the lower frequency of apoptotic cells observed in restenotic tissue was attributable to both SMCs and macrophages. The key finding of less apoptosis in restenotic versus primary lesions was in agreement with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) analysis (2% versus 9%, P<0.001). For all lesions analyzed, significant inverse correlations were observed between the density of SMCs and the frequency of apoptotic cell death (r=-0.60, P<0.001) as well as the density of SMCs and that of macrophages (r=-0.74, P<0.001). No relationship was seen between the frequency of apoptosis and the density of macrophages. In conclusion, the data of the present study indicate that a low level of apoptosis may be an important mechanism leading to restenotic intimal lesion development after interventional procedures.

Adult↗
PubMed1997

[Decreased apoptosis as a pathogenic factor in intimal hyperplasia of human arteriosclerosis lesions].

Restenosis remains a persistent problem following intravascular reconstruction. Smooth muscle cell proliferation, extracellular matrix production and remodeling are accepted mechanisms of restenotic lesion formation. Decreased programmed cell death (apoptosis) may also contribute to restenosis by prolonging the life span of intimal cells, with their subsequent accumulation and development of hyperplastic lesions. The objectives of the present study were as follows: i) to identify cell death, ii) to distinguish and quantify apoptosis from necrosis, and iii) to compare restenotic with primary lesions. To this end, human atherectomy specimens from 25 primary and 14 restenotic coronary and peripheral lesions were studied by TUNEL test (TdT-mediated dUTP Nick End Labeling; detection of cell death by the presence of fragmented DNA), transmission electron microscopy and morphometric analysis. Intimal hyperplasia was more consistent with restenosis than with primary lesion origin, and was mainly attributed to increased smooth muscle cell density (649 vs. 219 cells/mm2; p < 0.001). The main finding of the present study is that hypercellular restenotic tissue contains fewer TUNEL+ cells than hypocellular plaques (14% vs. 27%; p < 0.05). Most importantly, ultrastructural evaluation revealed a markedly reduced portion of intimal plaque cells, especially smooth muscle cells exhibiting distinct morphologic signs of apoptosis (3% vs. 13%; p < 0.001). In contrast, incidence of necroses did not differ between both lesion types (0.13 vs. 0.12 necroses/ cell; p = 0.49). Thus, our data indicate apoptosis and not necrosis to be the crucial cell death form to account for the apparent discrepancy found in both lesion types with reduced apoptosis in cell-rich restenoses. The findings of the present study suggest that decreased apoptosis is an important regulatory mechanism ultimately leading to intimal hyperplasia as commonly found in human restenosis post angioplasty.

Aged↗
PubMed1997

[Increased apoptosis and necrosis of coronary plaques in unstable angina].

In acute coronary syndromes, arteriosclerotic plaques are characterized by inflammation and decreased smooth muscle cell density. The underlying pathogenic processes remain unclear. Among others, increased programmed cell death (apoptosis) is postulated. Coronary atherectomy specimens from 26 patients with unstable angina (group 1) and from 24 patients with stable angina (group 2) were examined, using immunohistochemistry (TUNEL test to detect fragmented DNA) and transmission electron microscopy. The objectives of the present study were to evaluate plaque group differences in the cellular composition, to detect and quantify cell death, and to differentiate between apoptosis and necrosis. Group 1 lesions contained more macrophages and lymphocytes as well as significantly (p = 0.01) less smooth muscle cells compared with group 2 lesions, whereas both revealed a comparable cell density. All plaques showed signals for fragmented DNA. TUNEL-positive cells were seen more frequently in lesions with unstable angina (p = 0.04). Ultrastructural analysis revealed signs of programmed cell death, such as nuclear alterations, cellular condensation due to lost adhesion, and apoptotic bodies. Importantly, group I lesions comprised significantly more apoptotic SMCs and apoptotic macrophages compared with group 2 lesions (28% vs. 16%; p = 0.02). Also, cellular necroses were found to be increased in lesions with unstable angina (18% vs. 8%; p = 0.02). The density of macrophages showed a positive correlation to the incidence of cellular necroses in group 1 lesions (r = 0.44; p = 0.02), but not in group 2 lesions. In both plaque groups, this determinant was independent from cellular apoptosis, also at high levels as found with unstable angina. The present study on coronary atherectomy specimens with unstable angina reveals intimal macrophage infiltration and the density of apoptotic as well as necrotic intimal cells to be increased, whereas the content of intact SMCs was reduced. Increased, macrophage-independent apoptosis strongly points to the presence of one or several pro-apoptotic intimal factor(s) predisposing to plaque rupture. Implications of our findings may be directed to identify this (these) factor(s) and to modulate endogenous apoptotic activity with the ultimate goal to raise regional smooth muscle cell density.

Angina, Unstable↗