Noninvasive quantitative tissue characterization and two-dimensional color-coded map of human atherosclerotic lesions using ultrasound integrated backscatter: comparison between histology and integrated backscatter images.

OBJECTIVES: The purpose of the present study was to define clinicopathologically whether integrated backscatter (IB) combined with conventional two-dimensional echo (2DE) can differentiate the tissue characteristics of calcification (CL), fibrosis (FI), lipid pool (LP) with fibrous cap, intimal hyperplasia (IH) and thrombus (TH) and can construct two-dimensional tissue plaque structure in vivo. BACKGROUND: It is difficult to characterize the components of plaque using conventional 2DE techniques. METHODS: Integrated backscatter values of plaques were measured in the right common carotid and femoral arteries (total 24 segments) both during life and after autopsy in 12 patients (age 68 to 84 years, 10 men and two women). Integrated backscatter values were determined using a 5-12 MHz multifrequency transducer, setting the region of interests (ROIs) (11 x 11 pixels) on the echo tomography of the entire arterial wall (55 +/- 10 ROI/segment) and comparing it with histologic features in the autopsied arterial specimens. RESULTS: Corrected IB values obtained before death and at autopsy were significantly correlated (r = 0.93, p < 0.01). Corresponding to the histologic features, corrected IB values on the rectangle ROIs obtained during life were divided into five categories: category 1 (TH) 4 < IB < or = 6; category 2 (media and IH or LP in the intima) 7 < IB < or = 13; category 3 (FI) 13 < IB < or = 18, category 4 (mixed lesion) 18 < IB < or = 27 and category 5 (CL) 28 < IB < or = 33. In category 2, media and intima were differentiated using conventional 2DE. Under the above procedures, color-coded maps constructed with IB-2DE obtained during life precisely reflected the histologic features of media and intima. CONCLUSIONS: Integrated backscatter with 2DE represents a useful noninvasive tool for evaluating the tissue structure of human plaque.

Fifteen-year follow-up of a heterozygous Fabry's disease patient associated with pre-excitation syndrome.

A 47-year-old woman with heterozygous Fabry's disease with pre-excitation syndrome has been followed up for 15 years. Diagnosis was confirmed by the typical electron microscopic feature of the endomyocardial specimen and a decreased plasma alpha-galactosidase activity. As the disease progressed, the interventricular septum thickened from 11 to 17 mm as measured by echocardiography, while the AH interval was prolonged from 80 to 140 msec. In Fabry's disease, the PR interval has been reported to be variable from short PR to AV block. Therefore, this case may be helpful to understand the time course in the AV conduction abnormalities with the progression of Fabry's disease.

Washout of I-123 meta-iodobenzylguanidine for assessing cardiac sympathetic activity with progression of hypertension in Dahl salt-sensitive rats.

BACKGROUND: To evaluate cardiac sympathetic activity, a simple method should be developed to replace such complex methods as the spillover rate of tritiated norepinephrine (3H-norepinephrine) or microneurography of sympathetic nerve activity. The goal of this study is to evaluate cardiac sympathetic activities by analyzing the washout of I-123 meta-iodobenzylguanidine (123I-MIBG), a radiolabeled norepinephrine analogue, in Dahl salt-sensitive (DS) rats as it relates to the progression of hypertension. METHODS AND RESULTS: Dahl salt-resistant (DR) rats and DS rats were fed an 8 % salt diet starting at age 5 weeks. Marked hypertension and cardiac hypertrophy developed in the DS rats, whereas DR rats remained normotensive. Then the time-activity curves of 123I-MIBG from 15 to 200 minutes were obtained from both DS and DR strains at ages 8, 11, and 13 weeks using dynamic scintigraphic analysis. We also examined the nonneuronal washout of 123I-MIBG using dynamic scintigraphic studies in desipramine pretreated normal rats. In the preliminary study with desipramine pretreatment, the majority of the nonneuronal 123I-MIBG washout occurred by 90 minutes after injection. Therefore the late-phase washout in the control rats was found to reflect the neuronal washout. We then applied exponential curve fitting to the time activity curves acquired in the 90- to 200-minute period after 123I-MIBG injection in both DR and DS rats. When we compared the coefficients of these washout curves in the DS and DR rats as an index of cardiac sympathetic activities, the coefficient values remained high during all stages in DS rats, whereas they decreased with age in DR rats. CONCLUSION: Measurement of late-phase 123I-MIBG washout may be a useful tool for assessing the change in sympathetic activity in the progression of hypertension without the influence of extraneuronal washout of 123I-MIBG and left ventricular hypertrophy.

Mode and role of cell death during progression of atherosclerotic lesions in hypercholesterolemic rabbits.

Two cell types, macrophages and smooth muscle cells (SMCs), play important roles in the development of atherosclerotic lesions. Both contribute to the formation of the lesions not only by their presence but also by taking in or releasing extracellular substrates during life and at death. The present study aimed to elucidate their turnover, focusing on the detailed description of the modes of death in each cell type, and the roles of their death in the progression from early into advanced atherosclerotic lesions. Ascending aortas were obtained from New Zealand white male rabbits fed a diet with 1% cholesterol for 3 months (3-M group, n= 6) and 6 months (6-M group, n = 6). They were histologically examined, and the cell death was checked by in situ nick end-labeling (TUNEL), using a Taq polymerase-based in situ ligation assay with/without combination of immunohistochemistry, electron microscopy (EM), and TUNEL at the EM level. Intimal hyperplasia and luminal stenosis advanced with increased dietary interval, and the aortic intima of the 3-M group consisted of histological types I-III atherosclerotic lesions, whereas that of the 6-M group included types III-V. Along with the progression, the cellular population decreased, but the area of fibrosis increased. The percentage area of macrophages declined (from 60% +/- 5% to 23% +/- 2%), but that of SMCs increased (from 5% +/- 1% to 10% +/- 2%). The positive cells for in situ ligation were less frequent in the 6-M group (0.05% +/- 0.01%) than in the 3-M group (0.2% +/- 0.04%), which was due to a decrease in SMCs positive for in situ ligation. The frequency of TUNEL-positive cells was higher than that of in situ ligation-positive cells in both groups, suggesting that cell death involved not only apoptosis but also oncosis. This was confirmed using EM: cell death occurred via both apoptosis and oncosis. EM-TUNEL positively labeled not only apoptotic but also some oncotic nuclei. Death of macrophages and SMCs involves both apoptosis and oncosis in the aortic intima of hypercholesterolemic rabbits. Decline in the dying rate of SMCs might be associated with the formation of SMC-rich and collagen-rich lesions in the late advanced stage of atherosclerosis, although such a cause-effect relationship is to be further confirmed.

Estimation of left ventricular contractile performance in atrial fibrillation: experimental and clinical studies.

There are few studies regarding the assessment of left ventricular contractile function in patients with atrial fibrillation (AF). The aim of this study was to assess the left ventricular (LV) contractile function, i.e., the end-systolic pressure-volume relation (Ees) and a recently developed LV systolic myocardial stiffness constant (Ksm), without load manipulation in AF. In an experimental study of acute AF in dogs (n = 5), we were able to assess these indexes of the LV contractile function during acute AF, and found that the values were similar to those obtained during occlusion of the inferior vena cava (IVC) at the baseline state. During rapid ventricular pacing (140 or 160 bpm), the indices of LV contractile function increased due to the force-frequency relation (4.56 +/- 1.85, Ees baseline; 6.42 +/- 2.54*+, Ees pacing; 5.15 +/- 2.01 mmHg/ml, Ees AF; *P < 0.05 vs baseline, +P < 0.05 vs. AF)(4.73 +/- 0.48, Ksm baseline; 6.24 +/- 1.12*+, Ksm pacing; 3.99 +/- 1.14, Ksm AF; *P < 0.05 vs baseline, +P < 0.05 vs AF). In a study of chronic clinical AF in patients without heart disease (lone AF, n = 7), the indexes of LV contractile function were preserved compared with those of control patients (CTL, n = 10) obtained during IVC occlusion; the values were decreased in patients with both AF and dilated cardiomyopathy (AFDCM, n = 5)(2.5 +/- 1.1, Ees CTL; 2.4 +/- 0.4, Ees lone AF; 1.1 +/- 0.3 mmHg/ml*+, Ees AFDCM; *P < 0.05 vs CTL, +P < 0.05 vs lone AF)(5.3 +/- 1.8, Ksm CTL; 4.9 +/- 1.6, Ksm lone AF; 2.7 +/- 0.2*+, Ksm AFDCM; *P < 0.05 vs CTL, +P < 0.05 vs lone AF). Thus, during acute AF in dogs and in chronic AF patients, LV contractile function was assessed without load manipulation. In both the acute AF dogs and the chronic lone AF patients, LV contractile function was preserved, and in the AFDCM patients it was depressed.