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.
Late potentials are very small signals (1-20 microV) in the surface ECG with high-frequency components, which are found in patients prone to sustained ventricular tachycardia. Evaluation of these signals requires either very sophisticated recording techniques for single-beat analysis or signal averaging. Signal averaging, however, might disregard information about risk stratification. Therefore, we developed the Single-Beat Spectral Variance (SBSV) based on two-dimensional (2-D) Fourier transform of 80 ms segments of 128 consecutive beats. This approach depicts the beat-to-beat variability of the frequency contents of these ECG segments. An index function enables an objective detection of late potentials. We investigated 35 patients after myocardial infarction and sustained ventricular tachycardia (Group 1), 50 patients after myocardial infarction without ventricular arrhythmias (Group 2) and ten healthy volunteers. SBSV classified 29 of 35 patients (83%) of Group 1 as pathologic, 14 of these 29 patients (48%) exclusively on the basis of marked Wenckebach-like conduction pattern. In Group 2, only five of 50 patients showed abnormal SBSV. In Group 3, we found no pathologic result. Thus, SBSV is a promising new method to investigate late potentials in patients after myocardial infarction. SBSV contains not only the results of frequency analysis after signal averaging, but also evaluates variable ECG components.
Objective: Exercise induced ischemia or heart rate acceleration may unmask late potentials or provoke functional changes, which might be important factors to improve the low positive predictive value of late potential analysis at rest for postinfarction risk stratification. However, methodological refinements are required to detect late potentials with exercise. Methods: We, therefore, investigated the surface‐electrocardiogram in 100 patients after myocardial infarction (50 with sustained ventricular tachycardia [group I], 50 patients without ventricular arrhythmias [group II], and in 15 normals before and immediately after bicycle exercise test using Spectrotemporal Mapping (STM) with fast Fourier transform (FFT) and Simson method and introduced selective signal averaging. Results: In group I, 30 out of 50 patients showed late potentials at rest, after selective signal averaging also recognizable immediately after exercise in all of these patients, however, with a time‐shift of 18 ± 13 ms into the ST‐segment. Twelve out of 50 patients of group I with only transient late potentials tended to have inducible and recurrent ventricular tachycardia with a shorter cycle length. In group II, 4 out of 50 patients had late potentials at rest and 2 out of 46 patients developed them during exercise. Transient pathological Simson method was associated with transmural ischemia. Conclusions: Thus, detection of the effects of exercise on late potential analysis is possible with selective signal averaging immediately after exercise. Exercise unmasks late potentials not detectable at rest by their time‐shift into the ST‐segment. Using this method, patients that would have been lost with conventional late potential analysis, could be identified.
Our knowledge ofthe identity and functional significance ofthe pathogenic mechanisms responsible,f'or restenosis and arteriosclerosis in man is still limited. Among others, phenotypic conversion, migration, and proliferation qf smooth muscle cells have been suggested to lead to hypercellular neointima. In the present study, w*e examined intimul cell numbers and cell types in tissue of 23 postangioplasty lesions biop.ried by directional utherectorn~. using histohgy and transmission electron microscopv. Cornparative tissue analysis was p e t j h n e d f i r 53 primar?; lesions. Ti.ssue specimens obtained from coronaty ( n = 32) and peripheral lesions (n = 44) of 69 svrnptornatic patients were analyzed. Histological assessment of cell density showed intra-and interlesionol iwriability. A marked1.y ( P < 0.001) higher cellularity wus found in postangioplasty compared to primary lesions, irrespectiiv of coronary or peripheral origin. Cell density in renarrowed tissue following angioplasty ( 2 to 30 months) did riot significantly decrease regardless of previous balloon dilatation or atherectorry. When categorizing intimal cell density, postangioplasty lesion hypercellularity (7Sth percentile; > 514 cells/mm') was observed in 12/23 lesions (52%), but hvpocellularity (25th percentile; < 76 cells/mni') in none. In contrast. primary lesions were more inricible, with hypercellularity in 7/53 plaques (13%). and hypocetlularity in 19/53 (36%). Trunsmission electron microscopic analysis of subcellular features revealed hypocellulctr plaques to have an extensive build-up of extracellular matrix, with only sparsely embedded smooth muscle cells (SMCs). These SMCs haw a range qf' intermediate to microfilament-rich contractile phenotypes. thereby indicating only marginal metabolic cicti\,ity. I n contrust, hypercellular plaque regions contained predoniiriantly organelle-filled SMCs. irrespective qf po.c.tungiaplasty or primary origin. In conclusion, increased SMC density was observed predominantly in most renarrowed lesions encompassing classical restenoses (2 to 6 months post angioplasty) as well a.s late recurrent lesions (7 to 30 months postangioplasty). Concordundy, primary lesion hypercellularity is suggested to be related to the formation and progression of nutiw arteriosclerosis. (J Interven Cardiol 1991; 10:417-425)
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