Association between cardiac function and pulmonary function in hypertensive patients.

OBJECTIVE: This study examined the association between cardiac function and pulmonary function in hypertensive patients. METHODS: Hypertensive patients without overt cardiovascular disease were enrolled (n=43; mean±SD age 71±9 years). Pulmonary function was measured by the percentage of predicted forced vital capacity (%FVC) and the ratio of 1 s forced expiratory volume (FEV1) to FVC (FEV1/FVC ratio). Left ventricular ejection fraction (LVEF) and the ratio of peak early diastolic transmitral flow (E) to peak early diastolic mitral annular velocity (e') (E/e' ratio) were assessed using echocardiography. RESULTS: Multiple linear regression analysis revealed that E/e' was independently associated with %FVC and that LVEF was independently associated with FEV1/FVC ratio. Both LVEF and FEV1/FVC ratio were significantly lower in hypertensive former or current smokers than in hypertensive never smokers. CONCLUSIONS: Subclinical cardiac dysfunction was independently associated with reduced pulmonary function in hypertensive patients. Hypertensive patients with decreased pulmonary function may need preventive care to prevent the progression of heart failure.

Differences in left ventricular diastolic dysfunction between eccentric and concentric left ventricular hypertrophy in hypertensive patients with preserved systolic function.

Left ventricular (LV) hypertrophy (LVH) may be eccentric or concentric (2 × LV posterior wall thickness relative to LV end-diastolic dimension ≤ 0.42 or > 0.42, respectively). The LV diastolic function between age-matched hypertensive patients with eccentric and concentric LVH was compared in the present study. Echocardiography was used to measure LV mass index (LV mass/body surface area; LVMI) as an index of LVH. LV diastolic function was assessed by measurements of peak early transmitral flow velocity (E)/peak late transmitral flow velocity (A) (the E/A ratio), peak early diastolic mitral annular velocity (e') and the E/e' ratio. Although LVMI, E/A and e' did not differ between the two groups, E/e' was significantly higher (worse) in patients with concentric LVH (13.4 ± 5.4) than in those with eccentric LVH (11.1 ± 3.6). Among hypertensive patients with LVH, those with concentric LVH may, therefore, have more severe LV diastolic dysfunction than those with eccentric LVH even if their LVMIs, which reflect the degree of LVH, are similar.

Aortic root dilatation as a marker of subclinical left ventricular diastolic dysfunction in patients with cardiovascular risk factors.

Consensus is lacking about the clinical importance of aortic root dilatation in assessment of the risk of cardiovascular disease. In this study, correlations between aortic root diameter and echocardiographic features of left ventricular (LV) diastolic function were investigated in 333 patients with at least one cardiovascular risk factor (hypertension, diabetes or dyslipidaemia) and preserved LV systolic function. Aortic root diameter was measured by M-mode echocardiography, and LV diastolic function was evaluated by measuring the peak velocity of early (E) and late (A) diastolic transmitral blood flow and peak early diastolic mitral annular velocity (E') by Doppler echocardiography. Linear regression analysis showed that, in men, age was not related to aortic root diameter but hypertension and LV hypertrophy were, whereas the converse was true in women. The parameters E, E/A ratio and E', were related to aortic root diameter in both sexes. Stepwise multiple regression analysis confirmed that E in women and E' in men were independently associated with aortic root diameter. It is concluded that aortic root dilatation might be a useful marker of subclinical LV diastolic dysfunction. Patients with preserved systolic function showing aortic root dilatation should, therefore, be given preventative therapy against LV diastolic heart failure.

Exendin-4 regulates the expression of the ATP-binding cassette transporter A1 via transcriptional factor PREB in the pancreatic ß cell line.

BACKGROUND: PRL regulatory element-binding (PREB) protein is a transcription factor that regulates insulin promoter activity in the rat anterior pituitary. The PREB protein is expressed not only in the anterior pituitary but also in pancreatic ß cells. Previously, we have reported that PREB plays an important role in glucose-mediated insulin gene expression in pancreatic ß cells. The ATP-binding cassette transporter A1 (ABCA1) in pancreatic ß cells influences insulin secretion and glucose homeostasis. Exendin-4 (Ex-4), a longacting agonist of the glucagon-like peptide 1, stimulates ABCA1 expression in pancreatic ß cells. AIMS: In this study, we examined the role played by PREB in Ex-4-induced ABCA1 expression in pancreatic ß cells. MATERIAL/SUBJECTS AND METHODS: PREB mRNA and protein expression were evaluated in pancreatic ß cell line (INS-1 cells) treated with Ex-4 (10 nM). RESULTS: Ex-4 stimulated PREB protein and mRNA expression in INS-1 cells. PREB stimulated the activity of the luciferase reporter protein that was under the control of the ABCA1 promoter. Chromatin immunoprecipitation assay showed that PREB mediates its transcriptional activity by directly binding to the ABCA1 promoter region. Finally, we used small interfering RNA to inhibit PREB expression in the cells and demonstrated that the knockdown of PREB expression attenuated the effects of Ex-4 on ABCA1 expression. CONCLUSION: PREB mediates Ex-4-stimulated transcription of the ABCA1 gene in pancreatic ß cells.

Raloxifene inhibits menin-dependent estrogen receptor activation in breast cancer cells.

BACKGROUND: Menin is a tumor suppressor encoded by Men1 that is mutated in the human-inherited tumor syndrome--multiple endocrine neoplasia type 1. Menin binds to estrogen receptors (ER) to enhance estrogen activity in breast cancer cells. AIM: Our clinical study showed that the outcome in the case of menin-positive tumors was worse than in the case of menin-negative tumors. We examined the role of raloxifene on the cell growth in a menin-positive breast cancer cell line. MATERIAL AND METHODS: To examine the mechanism of raloxifene on menin-dependent activation of ER, we employed the mammalian two-hybrid system. We have established a breast cancer cell line that stably expresses menin. Using these cells, we have examined the effect of raloxifene and tamoxifen on cell growth of menin-transfected cells. RESULTS: The expression of activation function (AF)-2 enhanced menin-mediated luciferase expression in the mammalian two-hybrid assay. Raloxifene attenuated the effect of menin on estrogen response element-luciferase activation, indicating that raloxifene inhibited the binding of menin to AF-2. Raloxifene significantly inhibited the growth of menin-transfected cells in a dose-dependent manner. Tamoxifen also inhibited menin-transfected MCF-7 cells; however, this inhibition was much less than that of raloxifene. CONCLUSION: Raloxifene inhibits the binding of menin to the AF-2 domain of ERα, suggesting that raloxifene is one of the therapeutic options for menin-positive breast cancer.

Hyperglycemia suppresses ABCA1 expression in vascular smooth muscle cells.

Hyperglycemia is a major risk factor for atherosclerotic disease. The ATP-binding cassette transporter A1 (ABCA1) functions as a pivotal regulator of lipid efflux from cells to apolipoproteins and is thus involved in lowering the risk of atherosclerosis. In this study, we have examined the glucose-mediated regulation of the ABCA1 gene expression in vascular smooth muscle cells. ABCA1 expression was examined by real-time polymerase chain reaction (PCR), Western blot analysis, and reporter gene assay. The results showed that the expression of the ABCA1 mRNA and protein decreased after the cells were treated with 22.4 mM glucose for 48 h. The transcriptional activity of the ABCA1 promoter paralleled the endogenous expression of the ABCA1 gene. Next, we used inhibitors of certain signal transduction pathways to demonstrate that the glucose-induced ABCA1 suppression is sensitive to the p38-mitogen-activated protein kinase (MAPK) inhibitors. The expression of a constitutively active form of p38-MAPK in the cells inhibited the ABCA1 promoter activity, irrespective of the presence of glucose. A dominant-negative mutant of p38-MAPK abrogated the inhibitory effect of glucose on the ABCA1 promoter activity. These results indicate that the glucose-induced suppression of ABCA1 expression is partially mediated by the activation of the p38-MAPK pathway.

Exendin-4 regulates glucokinase expression by CaMKK/CaMKIV pathway in pancreatic beta-cell line.

AIM: Glucokinase (GK) in pancreatic beta cells is thought to be involved in insulin secretion and glucose homeostasis. This study investigates whether the long-acting agonist of the glucagon-like peptide 1, namely exendin-4, mediates stimulatory effects on GK gene expression through the Ca(2+)/calmodulin (CaM)-dependent protein kinase (CaMK) cascade. METHODS: GK expression was examined by real-time PCR, western blot analysis and reporter gene assay in rat insulin-secreting INS-1 cells incubated with exendin-4. CaMKIV activity was assessed by detection of activation loop phosphorylation (Thr(196)) of CaMKIV. We investigated the effect of the constitutively active form (CaMKIVc) of CaMKIV on GK promoter activity. RESULTS: Increased expression level of GK protein was noted in response to rising concentrations of exendin-4 with maximum induction at 10 nM. Real-time PCR analysis showed a significant increase in the amount of GK mRNA in response to rising concentrations of exendin-4. Exendin-4 also stimulated GK promoter activity but failed to do so in the presence of STO-609, a CaMKK inhibitor. This result is consistent with the observations that the upregulation of CaMKIV phosphorylation (at Thr(196)) peaked after 15 min of exposure to exendin-4 and that CaMKIVc enhanced or upregulated GK promoter activity in INS-1 cells. Furthermore, STO-609 significantly suppressed the exendin-4 - upregulated the expression of the GK protein. CONCLUSION: Activation of the CaMKK/CaMKIV cascade might be required for exendin-4-induced GK gene transcription, indicating that exendin-4 plays an important role in insulin secretion in pancreatic beta cells.

Antioxidant effect of a new calcium antagonist, azelnidipine, in cultured human arterial endothelial cells.

Azelnidipine is a novel dihydropyridine-type calcium antagonist with long-acting anti-hypertensive action and a low reported incidence of tachycardia. We aimed to evaluate its antioxidant activity in cultured human arterial endothelial cells under oxidative stress. Endothelial cells were exposed to 1 mM H2O2 and treated with 100 microM alpha-tocopherol, 1 nM, 10 nM or 100 nM azelnidipine, 100 nM nifedipine or 100 nM amlodipine. After 3 h, the cell number and level of lipid peroxidation were evaluated by measuring the total protein and 8-iso-PGF2 alpha concentrations, respectively. The total protein concentration was similar with each treatment. Inhibition of 8-iso-PGF2 alpha was greatest with 10 nM azelnidipine (compared with the other drugs); the difference between 10 nM and 100 nM azelnidipine was not significant. We conclude that azelnidipine has a potent antioxidative effect that could be of significant clinical benefit when combined with its long-lasting anti-hypertensive action and low incidence of tachycardia.

Accuracy and reproducibility of coronary flow rate assessment by real-time contrast echocardiography: in vitro and in vivo studies.

Real-time myocardial contrast echo (MCE) provides the potential to assess myocardial blood flow from time-intensity refilling curves after high-energy bubble destruction. This study validated the accuracy of this approach and the effect of specific examination variables and instrument settings on results. The effects of examination depth and angle as well as dynamic range, pulse repetition frequency, and line density were assessed with the use of in vitro incremental flow rates produced in an in vitro tissue phantom. In vivo recordings of real-time imaging with an infusion of a contrast agent (Optison) were obtained in 7 open-chest dogs with graded left anterior descending artery stenosis at baseline and during adenosine hyperemia, and were compared with flow probe measurements. After bubble destruction, time-intensity data were fitted to an exponential function, and the rate of intensity increase (b) and peak plateau intensity (A) were derived from refilling curves. In vivo real-time values for b, but not A, correlated closely with flow probe measures (r = 0.93). A similar correlation for b was observed in vitro (r = 0.98). The correlation between flow rate and b was influenced by several examination variables, including depth, angle, and instrument settings. Real-time MCE provides accurate quantification of coronary flow by assessing the rate of microbubble refilling. However, this parameter may be affected by several examination and instrument variables. Therefore, real-time MCE refilling measures are best applied by comparing baseline values with those of stress studies.

Influence of the angiotensin II receptor antagonist losartan on diuretic-induced metabolic effects in elderly hypertensive patients: comparison with a calcium channel blocker.

OBJECTIVE: Diuretic therapy frequently induces undesirable biochemical changes and side effects. We compared metabolic effects of a low-dose diuretic (D) given in combination with an angiotensin II receptor antagonist, losartan (L), with those resulting from a diuretic given in combination with a calcium channel blocker, slow-release nifedipine (N). MATERIAL AND METHODS: Thirty-seven elderly patients with mild to moderate hypertension (mean age: 71 +/- 3 years) were treated with either L+D (n = 18) or N+D (n = 19) for 1 year. Diuretic therapy included low-dose trichlormethiazide or low-dose furosemide in numbers of patients that were similar between L+D and N+D groups. Blood pressure, serum electrolytes, uric acid, blood glucose, renal function and lipid parameters were measured at baseline, 6 months and 1 year. RESULTS: Effective blood pressure control was observed in both groups at 6 months, and with further improvement at 1 year. Serum potassium was significantly decreased from baseline at 6 months (p < 0.01) and 1 year (p < 0.01) in the N+D group, but not in the L+D group. Serum uric acid was significantly increased from baseline at 6 months (p < 0.01) and 1 year (p < 0.01) in the N+D group, but had minimally decreased at 1 year in the L+D group (p < 0.1). Blood glucose, renal function and lipid parameters did not change in either group. CONCLUSION: The combination of losartan and low-dose diuretics effectively treated hypertension in elderly patients while minimizing the metabolic consequences of diuretic therapy. Larger trials will be necessary to confirm this finding.

Ultrasonographic assessment of coronary flow reserve and abdominal fat in obesity.

Recent technological advances in transthoracic Doppler echocardiography (TTDE) have provided noninvasive measurement of coronary flow velocity reserve (CFVR). We aimed to quantitate a correlation between endothelial dysfunction and fat distribution. In 36 patients with obesity, 16 with noninsulin-dependent diabetes mellitus (DM) and 12 healthy volunteers, coronary flow velocity was measured at the distal site of the left anterior descending branch. CFVR was defined as the ratio of hyperemic (IV infusion of 0.15 mg/kg/min adenosine) to basal peak diastolic flow velocity. Abdominal wall fat index (AWFI) was estimated by ultrasonography. Insulin resistance was quantified by the euglycemic hyperinsulinemic clump method. AWFI was significantly related to CFVR (r = -0.46, p = 0.011) and insulin resistance (r = -0.71, p < 0.0001). CFVR could be noninvasively evaluated using TTDE. Coronary endothelial dysfunction indicated as CFVR, body fat distribution and insulin resistance was quantitatively correlated in obesity.

Comparison of real-time and intermittent triggered myocardial contrast echocardiography for quantification of coronary stenosis severity and transmural perfusion gradient.

BACKGROUND: Both intermittent triggered and real-time myocardial contrast echocardiography (MCE) have been proposed to detect impaired myocardial perfusion. We compared the ability of these 2 methods to quantify altered myocardial blood flow (MBF) and transmural distribution of MBF produced by graded coronary stenoses. METHODS AND RESULTS: In 8 open-chest dogs, we created 4 graded left anterior descending coronary artery (LAD) stenoses: 3 levels of reduced adenosine hyperemia (non-flow-limiting at rest) and 1 grade of flow-limiting at rest. Real-time MCE was performed with SonoVue infusion using low-energy power pulse inversion (ATL) imaging, whereas ECG-gated intermittent triggered imaging used high energy at pulsing intervals from 1:1 to 1:10. LAD signal intensity (SI) was plotted versus time by real-time MCE and versus pulsing intervals by triggered MCE and was fitted to a 1-exponential function to obtain plateau SI (A) and the rate of SI rise (b). Visual detection of decreased opacification was equivalent by triggered and real-time MCE. Fluorescent microsphere-derived MBF ratio in LAD/left circumflex artery beds demonstrated close correlation with both real-time imaging (b, r=0.79; Axb, r=0.81) and triggered imaging (b, r=0.78; Axb, r=0.80). The endocardial/epicardial ratio of MBF in the LAD bed demonstrated closer correlation with the endocardial/epicardial ratios of b (r=0.71) and Axb (r=0.67) obtained by real-time than triggered imaging (b, r=0.42; Axb, r=0.52). CONCLUSIONS: Real-time and triggered MCE are equivalent in their ability to identify coronary stenosis and quantify altered MBF.

Characterization of contraction and perfusion in the lateral border zone between normal and ischemic myocardium following coronary occlusion by myocardial contrast echocardiography.

We performed myocardial contrast echocardography with power Doppler imaging during left anterior descending occlusion in 10 dogs, and found that video intensity and dyssynergy in lateral border zones of ischemic myocardium were present, but the video intensity was significantly lower than adjacent nonischemic zones. The results of this study demonstrate that levels of perfusion and contraction, which are intermediate between normal and central ischemic zones, are observed in the border zone with coronary occlusion by myocardial contrast echocardography, and may have implications in identifying myocardium that will be spared necrosis and in measuring ultimate infarct size.

Quantitative assessment of myocardial perfusion during graded coronary stenosis by real-time myocardial contrast echo refilling curves.

OBJECTIVES: The present study examined the ability of real-time myocardial contrast echocardiography (MCE) to delineate abnormalities produced by graded coronary stenoses and to correlate signal intensity (SI) parameters derived from destruction/refilling curves with regional myocardial blood flow (MBF) and contractile function. BACKGROUND: Recent technological advances have enabled myocardial opacification by MCE to be achieved during real-time imaging. METHODS: In eight open-chest dogs, we created LAD occlusion and graded stenoses that were either flow-limiting at rest (FLS) or reduced adenosine hyperemia (non-flow-limiting at rest = NFLS). Myocardial contrast echo used Optison infusion and low-energy real-time power pulse inversion imaging. High-energy FLASH frames destroyed bubbles every 15 cardiac cycles. Myocardial SI-versus-time plots were fitted to a one-exponential function to obtain the rate of SI rise (b) and peak SI in the last frame. RESULTS: Dyssynergy was not observed during any NFLS, but perfusion abnormalities were. Visual detection of decreased opacification was possible with severe NFLS and FLS. b demonstrated a significant reduction with severe NFLS and near significant with moderate NFLS; peak SI did not. All exponential parameters were significantly decreased with FL stenosis and occlusion. The MBF ratio in LAD/LCx beds (fluorescent microspheres) correlated with b (r = 0.79) and the product of the peak SI and b (r = 0.80). CONCLUSIONS: In an open-chest dog model, parameters derived from microbubble refilling of the imaging field by real-time MCE correlate well with myocardial blood flow and can identify coronary stenosis.

Effect of cibenzoline, a class ia antiarrhythmic agent, on left ventricular diastolic function in hypertrophic cardiomyopathy.

We aimed to investigate whether the improvement of left ventricular (LV) diastolic function by cibenzoline, a class Ia antiarrhythmic drug, in hypertrophic obstructive cardiomyopathy (HOCM) is due to LV afterload reduction or a primary lusitropic effect on LV. Twenty-three patients with hypertrophic cardiomyopathy (11; HOCM, 12; non-obstructive HCM; HNCM) were examined. Pulsed-wave Doppler, color M-mode and tissue Doppler echocardiography were performed before and 90 minutes after oral administration of cibenzoline (300 mg), and were compared with a treatment of bisoprolol (5 mg/day, 10 days). Early (E) and late diastolic LV inflow velocity, E flow propagation velocity (FPV) and early diastolic mitral annulus velocity (Ea) were measured. E/FPV and E/Ea were calculated as indices of LV filling pressure. LV outflow pressure gradients estimated using continuous-wave Doppler in HOCM markedly decreased after cibenzoline (83 +/- 42 to 40 +/- 33 mmHg, p < 0.005) and bisoprolol (44 +/- 40 mmHg, p < 0.005). Following cibenzoline, E/FPV and E/Ea were significantly decreased in both HOCM (1.75 +/- 0.53 to 1.32 +/- 0.28, p < 0.05, 18.9 +/- 6.2 to 14.8 +/- 5.0, p < 0.05, respectively) and HNCM (1.75 +/- 0.58 to 1.41 +/- 0.73, p< 0.05, 13.0 +/- 4.3 to 9.7 +/- 3.6, p< 0.01, respectively). Those in HNCM did not change by bisoprolol. Cibenzoline improved LV diastolic function in HCM, whereas bisoprolol did not affect it. Thus, the primary lusitropic effect of cibenzoline rather than LV after load reduction might have contributed to the improvement of diastolic function in HOCM.

Physical properties of the mitral valve tissue assessed by tissue sound speed in cardiac amyloidosis: relationship to the severity of mitral regurgitation.

Cardiac amyloidosis has been documented to show mitral regurgitation (MR) and a thickened mitral valve (MV) due to amyloid deposits. However, the changes in the physical properties of the thickened MV tissue in cardiac amyloidosis, which may be a causative factor of the MR, have not been described. Physical properties of the tissue, which are expressed by the elastic bulk modulus, can be evaluated by tissue sound speed. If biological tissue is assumed to be fluid-like, the tissue sound speed may be given by c= square root of K/rho, where c is the tissue sound speed, K is the elastic bulk modulus, and rho is the density. A reduction in tissue sound speed indicates a reduction in the elastic bulk modulus of the tissue, assuming that there is little change in rho. This suggests that the tissue is less elastic. The purpose of this study was to assess the physical properties of MV tissue by evaluating the sound speed of the MV tissue in cardiac amyloidosis. MV specimens were obtained at autopsy from 20 control adults without cardiovascular diseases and from 20 patients with cardiac amyloidosis. An acoustic microscope operating at 450 MHz was used to measure the tissue sound speed in the tip and basal portions of the MV tissue. The density of MV tissue was measured by microgravimetry. The severity of the MR had been evaluated by Doppler echocardiography before death, and it was compared with the tissue sound speed measured after death. In cardiac amyloidosis showing mild MR, the tissue sound speed of the MV in the tip portion (1605 +/- 19 m/s) and in the basal portion (1791 +/- 64 m/s) were lower than the corresponding values in control subjects (1637 +/- 42 m/s and 1851 +/- 62 m/s). However, these differences were not statistically significant. In cardiac amyloidosis showing moderate MR, the tissue sound speed of MV in the tip portion (1563 +/- 17 m/s) and in the basal portion (1654 +/- 59 m/s) were significantly lower than the corresponding values in the control subjects (p < 0.001) and the patients with mild MR (p < 0.05). No significant differences were observed in the density of MV tissue among the three groups. Therefore, the low value of the MV tissue sound speed in patients with cardiac amyloidosis indicated a reduced elastic bulk modulus, suggesting the less elasticity of the MV tissue. Furthermore, the patients with moderate MR demonstrated the greater reduction in the tissue sound speed than the patients with mild MR. The data suggest that the changes in physical properties of the MV tissue may be one of the causes of MR in cardiac amyloidosis.

Assessment of coronary stenosis severity and transmural perfusion gradient by myocardial contrast echocardiography: comparison of gray-scale B-mode with power Doppler imaging.

BACKGROUND: The present study (1) compared the ability of power Doppler imaging with that of gray-scale B-mode tissue imaging to opacify the myocardium and detect coronary stenosis by myocardial contrast echocardiography and (2) compared the response of video intensity (VI) to variable pulsing intervals for each modality. METHODS AND RESULTS: Four grades of left anterior descending coronary artery (LAD) stenoses were created in 9 open-chest dogs. Stenoses reduced resting LAD flow by 25%, 50%, 75%, and 100% of baseline by flow probe. Myocardial contrast echocardiography was performed during varying ECG gated pulsing intervals (PIs) from 1:1 to 1:10. By gray-scale imaging, background-subtracted LAD bed VI was less than baseline VI at all PIs for the 100% reduced-flow state but not for any other flow state or interval. By power Doppler imaging, LAD bed VI was less than baseline VI at all intervals for 75% and 100% reduced-flow states but only 1:1 and 1:2 for 25% and 50% reduced-flow states, respectively. Correlation of VI and myocardial blood flow (determined by use of fluorescent microspheres) ratios from stenosed versus normal beds was stronger by power Doppler imaging. A transmural opacification gradient with stenosis was visualized and measured by power Doppler imaging, but it was insignificant by gray-scale imaging. The ratio of endocardial/epicardial flow determined by use of fluorescent microspheres was correlated with VI by power Doppler imaging at all PIs. CONCLUSIONS: Power Doppler imaging has advantages compared with gray-scale imaging in opacifying the myocardium and in detecting coronary stenosis and altered transmural distribution of myocardial perfusion from peak VI. Because VI differences from baseline at long PI vary for mild versus severe (75% and 100%, respectively) reduced-flow states, power Doppler imaging may provide a method to quantify coronary stenoses.

Evaluation of progression in nonrheumatic aortic valvular stenosis by scanning acoustic microscopy.

To investigate distributions of hardness and thickness in nonrheumatic aortic stenosis (AS), scanning acoustic microscopy was used. The acoustic propagation speed (APS: m/s) and thickness at three sites (tip, middle and base) of aortic valve were measured in 18 cusps from 7 surgical patients with AS (late lesion), 27 showing mild lesions from 9 autopsy cases (early lesion) and 18 healthy from 6 autopsy cases (healthy). These were measured in each layer of cusps: fibrosa (F), spongiosa (S) or ventricularis (V). In early lesions, an increase in APS preceded the thickening and distributed in the tip (1666 +/- 107), the three layers of the middle (F: 1782 +/- 121; S: 1590 +/- 38; V: 1636 +/- 59) and the fibrosa of the base (1736 +/- 203). In late lesions, APS of the tip and three layers of the base were markedly increased. Progressive nonrheumatic AS is characterized by increased hardness that precedes the thickening, and its distribution may be related to mechanical stress.

Comparison of left ventricular diastolic filling with myocyte bulk modulus using Doppler echocardiography and acoustic microscopy in pressure-overload left ventricular hypertrophy and cardiac amyloidosis.

BACKGROUND: The myocardial bulk modulus has been described as the constitutive properties of the left ventricular (LV) wall and is measured as rho V2 (rho = density, V = sound speed) using acoustic microscopy. HYPOTHESIS: The study was undertaken to assess the relationship between the myocyte bulk modulus and transmitral inflow patterns in patients with pressure-overload LV hypertrophy (LVH) and cardiac amyloidosis (AMD). METHODS: In 8 patients with LVH, 8 with AMD, and 10 controls without heart disease, the transmitral inflow pattern was recorded by Doppler echocardiography before death, and myocardial tissue specimens were obtained at autopsy. The tissue density and sound speed in the myocytes were measured by microgravimetry and acoustic microscopy, respectively. The diameters of the myocytes were measured on histopathologic specimens stained by the elastica Van Gieson method. RESULTS: In the subendocardium, the myocyte bulk modulus was larger in LVH (2.98 x 10(9) N/m2, p < 0.001) and smaller in AMD (2.61 x 10(9) N/m2, p < 0.001) than in the controls (2.87 x 10(9) N/m2). The myocyte diameter in LVH (26 +/- 1 microns) was larger than that in the control (21 +/- 1 microns, p < 0.001) and AMD (20 +/- 1 microns, p < 0.001). The bulk modulus in the subendocardial myocyte significantly correlated with the deceleration time (DT) of the early transmitral inflow (r = 0.689, p = 0.028 in control, r = 0.774, p = 0.024 in LVH, and r = 0.786, p = 0.021 in AMD). CONCLUSION: The changes in the myocyte elasticity as represented by the bulk modulus were limited to the subendocardial layers and may be related to relaxation abnormalities in LVH and a reduction in LV compliance in AMD.