Deletion of platelet-derived growth factor receptor-ß improves diabetic nephropathy in Ca²âº/calmodulin-dependent protein kinase IIα (Thr286Asp) transgenic mice.

AIMS/HYPOTHESIS: The activation of platelet-derived growth factor receptor-ß (PDGFR-ß) signalling is increased in the glomeruli and tubules of diabetic animals. In this study, we examined the role of PDGFR-ß signalling during the development of diabetic nephropathy. METHODS: We recently generated pancreatic beta cell-specific Ca(2+)/calmodulin-dependent protein kinase IIα (Thr286Asp) transgenic mice (CaMKIIα mice), which show very high plasma glucose levels up to 55.5 mmol/l and exhibit the features of diabetic nephropathy. These mice were crossed with conditional knockout mice in which Pdgfr-ß (also known as Pdgfrb) was deleted postnatally. The effect of the deletion of the Pdgfr-ß gene on diabetic nephropathy in CaMKIIα mice was evaluated at 10 and 16 weeks of age. RESULTS: The plasma glucose concentrations and HbA(1c) levels were elevated in the CaMKIIα mice from 4 weeks of age. Variables indicative of diabetic nephropathy, such as an increased urinary albumin/creatinine ratio, kidney weight/body weight ratio and mesangial area/glomerular area ratio, were observed at 16 weeks of age. The postnatal deletion of the Pdgfr-ß gene significantly decreased the urinary albumin/creatinine ratio and mesangial area/glomerular area ratio without affecting the plasma glucose concentration. Furthermore, the increased oxidative stress in the kidneys of the CaMKIIα mice as shown by the increased urinary 8-hydroxydeoxyguanosine (8-OHdG) excretion and the increased expression of NAD(P)H oxidase 4 (NOX4), glutathione peroxidase 1 (GPX1) and manganese superoxide dismutase (MnSOD) was decreased by Pdgfr-ß gene deletion. CONCLUSIONS/INTERPRETATION: The activation of PDGFR-ß signalling contributes to the progress of diabetic nephropathy, with an increase in oxidative stress and mesangial expansion in CaMKIIα mice.

A crucial role of sialidase Neu1 in hyaluronan receptor function of CD44 in T helper type 2-mediated airway inflammation of murine acute asthmatic model.

CD44 is a highly glycosylated cell adhesion molecule that is involved in lymphocyte infiltration of inflamed tissues. We have demonstrated previously that sialic acid residues of CD44 negatively regulates its receptor function and CD44 plays an important role in the accumulation of T helper type 2 (Th2) cells in the airway of a murine model of acute asthma. Here we evaluated the role of sialidase in the hyaluronic acid (HA) receptor function of CD44 expressed on CD4+ T cells, as well as in the development of a mite antigen-induced murine model of acute asthma. Splenic CD4+ T cell binding of HA was examined with flow cytometry. Expression of sialidases (Neu1, Neu2, Neu3 and Neu4) in spleen cells was evaluated by quantitative real-time reverse transcription-polymerase chain reaction. Airway inflammation and airway hyperresponsiveness (AHR) were evaluated in the asthmatic Neu1-deficient mouse strain SM/J model. Splenic CD4+ T cells from asthmatic model mice displayed increased HA receptor activity of CD44 after culture with the antigen, along with characteristic parallel induction of sialidase (Neu1) expression. This induction of HA binding was suppressed significantly by a sialidase inhibitor and was not observed in SM/J mice. Th2 cytokine concentration and absolute number of Th2 cells in the bronchoalveolar lavage fluid, and AHR were decreased in SM/J mice. In conclusion, HA receptor activity of CD44 and acute asthmatic reactions, including Th2-mediated airway inflammation and AHR, are dependent upon Neu1 enzymatic activity. Our observation suggests that Neu1 may be a target molecule for the treatment of asthma.

A potential mechanism for regulating myosin I binding to membranes in vivo.

Myosin Is are associated with specific membranes, however, the mechanism for regulating their intracellular localization is unclear. As a first step towards understanding this mechanism, membrane rebinding assays using Dictyostelium myoB were performed. Crude, cytosolic myoB bound to intact, but not to NaOH-treated plasma membranes. In contrast, partially purified myoB binds to both intact and NaOH-treated plasma membranes. Chemical cross-linking of cytosolic myoB yielded several products, whereas none were found with the partially purified myoB. These results suggest a model where proteins regulating the specific binding of myoB to the plasma membrane may exist both in the cytosol and on the plasma membrane.

Aging-associated intrinsic defects in IgA production by murine Peyer's patch B cells stimulated by autoreactive Peyer's patch T cell hybridoma-derived B cell stimulatory factors (BSF).

Immune functions deteriorate with age, primarily as a result of alterations in the number and subpopulations of T cells of the immune system. In contrast, the B cell component of the immune system is generally affected by senescence only to a minor extent. In the present report, we stimulated murine Peyer's patch (PP) B cells by nonspecific multifunctional B cell stimulatory factors (BSF) secreted by one of several autoreactive (self-major histocompatibility complex (MHC)-class II antigen-responsive) T cell hybridoma clones derived from PP of syngeneic mature adult mice, and then determined in vitro whether aging-associated intrinsic defects could be demonstrated in the proliferation of, and the synthesis and secretion of mucosal IgA by, the BSF-activated B cells. This approach could be a useful new in vitro method for assessing the effect of senescence on B cell Ig production, especially that of IgA, in the gut-associated lymphoid tissue (GALT). Aged PP B cells stimulated by the autoreactive PP T cell-derived BSF proliferated more (P less than 0.05), contained larger amounts of IgA (nearly 10 times) and also secreted considerably more IgA (nearly 4.5 times) than did mature adult PP B cells. However, the ratio of intracellular dimeric (d) IgA to total IgA in the aged B cell lysates was significantly reduced (by approx. 44%) as was also the secreted dIgA (by approximately 50%). The augumentation of not only the proliferation, but also the synthesis and secretion of IgA in vitro along with reduced dIgA/total IgA ratios of BSF-stimulated aged PP B cells appears to be due to aging-related intrinsic defects. Alterations in intracellular regulatory mechanisms of B cells, mediated by B cell receptors for autoreactive T cell-derived BSF, could be largely responsible for the observed polyclonal B cell hyperreactivity, associated with senescence.

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.

Evaluation of acoustic properties of the live human smooth-muscle cell using scanning acoustic microscopy.

This study was performed to measure the acoustic propagation speed in live human aortic smooth-muscle cells (HASMC), using scanning acoustic microscopy (SAM) and a novel measurement theory that permits the measurement of the acoustic propagation speed in biological samples of unknown thickness. C-mode and X-Z-mode images of HASMC under three different conditions: growing (G); differential (D); and on hypotonic loading (H), were acquired using 100-MHz, 450-MHz and 600-MHz ultrasound. The images exhibit features related to the cell surface curvature and intracellular structure. The theory supporting the methodology is derived in this article and makes use of the interference fringes within the focusing lens of the high-frequency transducer. The propagation speed in the cells was calculated from the location of the interference fringe on the C-mode images and the fringe shift on the X-Y-mode images with 450-MHz ultrasound. The propagation speed in D (1624 +/- 16 m/s) was significantly higher than those in G (1571 +/- 14 m/s, p < 0.05) and H (1585 +/- 8 m/s, p < 0.05). Scanning acoustic microscope measurements, along with the described theory, are useful for studying the acoustic properties of live cells ex vivo and have applications in both pathophysiology and biomechanics.

Ultrasonic tissue characterization can predict beta-blocker efficacy in dilated cardiomyopathy.

The aim was to determine if the combination of cyclic variation of myocardial integrated backscatter (variation IB) and left ventricular mass measurements can predict the efficacy of beta-blocker treatment in dilated cardiomyopathy. In 32 patients, left ventricular mass and variation IB were measured at baseline and during 6 microg/kg/min dobutamine infusion before the initiation of beta-blocker therapy. Variation IB was measured at left and right ventricular halves in the ventricular septum. The baseline left ventricular mass index and transseptal variation IB gradient during dobutamine were significantly greater in the effective group (1.16 +/- 0.18 g/mL and 1.8 +/- 0.6 dB) than in the ineffective group (0.94 +/- 0.28 g/mL, p = 0.032 and 0.4 +/- 0.6 dB, p < 0.005). When both baseline left ventricular mass index > or = 1.05 g/mL and transseptal variation IB gradient during dobutamine > or = 1.5 dB were defined as predictive criteria for the effective group, the sensitivity was 78% and the specificity was 86%. Analysis of transseptal variation IB during dobutamine may provide useful information predicting the efficacy of beta-blocker therapy in dilated cardiomyopathy.

Relationship between myocardial tissue density measured by microgravimetry and sound speed measured by acoustic microscopy.

If myocardial tissue can be assumed to be fluid-like, myocardial tissue elasticity can be estimated by the sound speed of tissue based on the equation K = rho(c)2, where K is the elastic bulk modulus, rho is density, and c is the sound speed of tissue. However, little data exist regarding the relationship between the sound speed of tissue and tissue density. The purpose of the present study was to evaluate the relationship between the sound speed of tissue and tissue density of various diseased myocardia. Myocardial tissue specimens at autopsy were obtained from 10 control patients without cardiovascular disease, 8 patients with pressure overload left ventricular hypertrophy (POLVH), and 8 patients with cardiac amyloidosis (AMD). Myocardial tissue sound speed was measured using a scanning acoustic microscope operating in the frequency of 450 MHz, and tissue density was measured by microgravimetry. The sound speed in POLVH (1639 +/- 17 m/s) was higher and that in AMD (1565 +/- 11 m/s) was lower than that in control patients (1615 +/- 15 m/s) (p < 0.001) at the temperature of 20-22 degrees C. The density in POLVH (1.087 +/- 0.004 g/cm3) was higher and that in AMD (1.072 +/- 0.003 g/cm3) was lower than that in control patients (1.082 +/- 0.003 g/cm3) (p < 0.001). Tissue density correlated with sound speed in all three groups (r = 0.96, p < 0.001). Therefore, myocardial tissue sound speed data obtained by acoustic microscopy enabled us to evaluate tissue elasticity without measuring tissue density directly.

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.

A new approach for glomerular lesions: evaluation of scanning acoustic microscopy (SAM) for experimental glomerular disease in rats.

Most pathological evaluations using ordinary optical microscopy are usually qualitative and subjective. The beneficial properties of scanning acoustic microscopy (SAM) include not only observation of microstructure but also quantitative measurement of acoustic propagation speed, indicating the tissue elasticity. In this study, we examined the capability of SAM to evaluate pathological findings in glomeruli using anti-Thy.1 glomerulonephritis. Light microscopic observations of the glomeruli showed severe cell proliferation and mesangial matrix expansion at 10 days after induction of glomerulonephritis and, yet, to a lower extent at day 21 with onset of healing. C-mode scanning of SAM enabled imaging of glomerular structure compatible to findings of ordinary light microscopy. In addition, glomerular propagation speed in nephritic rats was significantly increased at day 10, and then decreased at day 21. These results indicate that SAM evaluation may be a new, useful technique for quantitative evaluation of proliferative glomerular lesions.

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.

Lipase-catalyzed kinetic resolution of 2,3-epoxy-1-tridecanol and its application to facile synthesis of (+)-disparlure.

Acylation of (+/-)-2,3-epoxy-1-tridecanol with acetic anhydride in diisopropyl ether by porcine pancreatic lipase yielded (2R, 3S)-2,3-epoxy-1-tridecanol as the remaining substrate with an optical purity of over 99% ee. (+)-Disparlure was synthesized in two steps from this optically active epoxy alcohol.

Treatment of ulcerative colitis with camostat mesilate, a serine protease inhibitor.

We were able to induce and maintain remission with camostat mesilate, a serine protease inhibitor, in two patients with ulcerative colitis, to whom salicylazosulfapyridine could not be administered due to previous side effects. The enzymatic activity of proteases from granulocyte, pancreatic juice and bacteria is possibly harmful to the inflamed colonic mucosa. Camostat mesilate can be expected to have an anti-inflammatory effect on the damaged mucosa of inflammatory bowel disease.

Left ventricular diastolic filling dynamics during isometric exertion in syndrome X assessed with Doppler flowmetry.

To study left ventricular diastolic properties in syndrome X, we analyzed transmitral filling dynamics during handgrip exertion. In 14 normal subjects (N), 17 with syndrome X (Syn X), 16 with single-vessel disease (SVD), and 8 with multiple-vessel disease (MVD), transmitral inflow was recorded at baseline and during handgrip (50% of maximal effort for one minute) using pulsed Doppler echocardiography. We measured early diastolic (E) and late atrial (A) inflow velocities, A/E ratio and percent change of A/E from baseline (%A/E). Blood pressure and heart rate increased to the same degree in each group during handgrip. In normal subjects, E did not change with handgrip; A (51 +/- 10 vs 54 +/- 11 cm/sec, P < 0.05) and A/E (1.16 +/- 0.22 vs 1.25 +/- 0.33, P < 0.05) increased minimally. In Syn X subjects, E decreased (51 +/- 10 vs 38 +/- 10 cm/sec, P < 0.0001), A increased (52 +/- 11 vs 60 +/- 14 cm/sec, P < 0.005), and A/E increased markedly (1.07 +/- 0.31 vs 1.68 +/- 0.51, P < 0.0001). The %A/E in Syn X and MVD were significantly larger than that in SVD and N (Syn X: 58 +/- 29%; MVD: 45 +/- 25%; SVD: 22 +/- 21%; N: 8 +/- 13%). Handgrip-induced changes in diastolic filling in syndrome X and are similar to those in MVD and more marked than in SVD. These changes are consistent with impaired ventricular relaxation and support a generalized left ventricular (LV) abnormality in syndrome X.

Cyclic variation of thickness in an age-related thick mitral valve observed by transthoracic echocardiography.

The cyclic variation of thickness during the cardiac cycle in age-related degenerative mitral valve (MV) has not been reported. Transthoracic echocardiography was used to evaluate the cyclic alteration in MV thickness in 40 patients with age-related MV thickening (diastolic MV thickness > or = 4 mm, age 70 +/- 14 years), 10 with mitral valve prolapse (MVP, age 49 +/- 11 years), 10 with rheumatic mitral stenosis (MS, age 66 +/- 9 years), and 31 control subjects (diastolic MV thickness < or = 3.6 mm, 53 +/- 17 years). After determination of the site of maximal thickness during diastole, the maximal and minimal thickness during systole of the anterior MV were measured. The percent change in MV thickness from diastole to systole (%deltaT) was calculated. The mitral regurgitation (MR) area was measured on color Doppler echocardiogram. The %deltaT (mean +/- sd) in age-related thickened MV and MVP groups were similar and significantly greater than that in control (60 +/- 8%, 61 +/- 6% vs 32 +/- 9%, p < 0.001). MR area was significantly greater in the age-related thickened MV group than that in controls (160 +/- 205 mm2 vs 14 +/- 40 mm2, p < 0.05). The %deltaT in MS (10 +/- 6%) was smallest (p < 0.001). A large cyclic alteration in valvular thickness was observed in the age-related degeneration of the MV and may be the cause of large MR despite no leaflet prolapse. The echocardiographic assessment of cyclic variation of MV thickness is feasible for estimating the histologic damage in thick MV.

Tissue characterization of myocardial cells by use of high-frequency acoustic microscopy: differential myocyte sound speed and its transmural variation in normal, pressure-overload hypertrophic, and amyloid myocardium.

The purpose of the present study was to evaluate the acoustic properties of myocytes in normal, pressure-overload hypertrophic, and amyloid myocardium. Myocardial tissue specimens at autopsy were obtained from 10 subjects without cardiovascular disease, six patients with left ventricular (LV) hypertrophy, and six patients with cardiac amyloidosis. Sound speed of myocytes was measured at subendocardial and subepicardial regions in myocardium by use of a high-frequency (450 MHz) acoustic microscope. In normal myocardium, the sound speed of myocytes was significantly higher in subendocardial region (1,728+/-19 m/sec) than in subepicardial region (1,645+/-22 m/sec) (p<0.0001). A significantly higher sound speed of myocytes was observed in the subendocardial region in LV hypertrophic myocardium (1,779+/-19 m/sec) than that in normal myocardium (p<0.001). In amyloid myocardium, a significantly lower sound speed of myocytes was observed in subendocardial (1,560+/-8 m/sec) and subepicardial (1,594+/-48 m/sec) regions than that in respective regions of the normal myocardium (p<0.0001 and p<0.05, respectively). Transmural variation in sound speed of myocytes measured by high-frequency acoustic microscopy existed in normal left ventricle. The differential myocyte sound speed and its transmural variation was observed in LV hypertrophic and amyloid myocardium as compared with normal myocardium. High-frequency acoustic microscopy can be a promising technique for myocardial tissue characterization at the myocyte level.

Evaluation of left atrial wall elasticity using acoustic microscopy.

Left atrial wall elasticity is one of the important factors regulating left atrial stiffness and functions. The authors evaluated left atrial wall elasticity by measuring the sound speed through the left atrial wall, based on the hypothesis that high elasticity tissues will yield larger sound speed values through the tissue, and examined age-associated changes in left atrial wall elasticity. Left atrium specimens were obtained from 30 normal subjects (age, 15-95 years) at autopsy. An acoustic microscope, operating at 450 MHz, was used to measure the sound speed in the endocardium and the myocardium of the left atrium. The sound speeds in endocardium and myocardium demonstrated significant correlation with age (r = 0.74, p<0.0001 and r = 0.47, p<0.01, respectively). These findings indicate that left atrial wall elasticity increased with advancing age. These changes may lead to deterioration of left atrial compliance and eventual left atrial failure in older subjects.

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.

A new modulation method with range resolution for ultrasonic Doppler flow sensing.

This paper proposes a new pair of sequences whose cross-correlation values are zero except for the peak value and presents a new modulation method for an ultrasonic Doppler flowmeter with high sensitivity utilizing these sequences. In this method, transmitted and received waves are modulated and demodulated, respectively, by the specified new sequences. Since ulfavourable reflected waves can be almost completely eliminated by this proposed modulation method, a high signal-to-noise ratio is easily achieved. Elementary experimental results are also given.

[An approach of in vivo measurement for ultrasonic myocardial tissue characterization].

The purpose of this study is to characterize regional myocardial alternations of reflected ultrasound throughout a cardiac cycle in normal and ischemic myocardium. Integrated ultrasonic backscatter (2-5 MHz) gated R wave of ECG was measured at the base, middle and apex in 4 dogs, and the apex before and after ischemia in other 4 dogs. Quantitative ultrasonic backscatter (IB) was reflected to a steel reflector. At the apex and middle, where a cyclic pattern of IB was discernible, maximum values were recorded near end diastole and minimum near end systole. The amplitude of the variation of IB throughout a cardiac cycle for each region increase progressively from base to middle to apex. Time-averaged IB over a cardiac cycle (averaged IB) was similar for each area of the heart (base = -50.6 +/- 0.5 dB (mean +/- SE), middle -49.4 +/- 0.5 dB, apex -49.7 +/- 0.6 dB. p = NS for comparison of any two regions). After occluding left anterior descending coronary artery for 30 minutes, the variation of IB was markedly blunted and averaged IB increased significantly (-47.5 +/- 0.5 dB. p less than 0.01 compared with preocclusion (-50.8 +/- 0.5 dB]. These results suggested that IB and averaged IB may permit assessment of intrinsic geometrical changes throughout a cardiac cycle (contractile properties) and histological changes respectively.