Novel quantitative assessment of myocardial perfusion by harmonic power Doppler imaging during myocardial contrast echocardiography.

OBJECTIVE: To test the hypothesis that the power of the received signal of harmonic power Doppler imaging (HPDI) is proportional to the bubble concentration under conditions of constant applied acoustic pressure, and to determine whether a new quantitative method can overcome the acoustic field inhomogeneity during myocardial contrast echocardiography (MCE) and identify perfusion abnormalities caused by myocardial infarction. METHODS: The relation between Levovist concentration and contrast signal intensity (CI) of HPDI was investigated in vitro under conditions of constant acoustic pressure. MCE was performed during continuous infusion of Levovist with intermittent HPDI every sixth cardiac cycle in 11 healthy subjects and 25 patients with previous myocardial infarction. In the apical views myocardial CI (CI(myo)) was quantified in five myocardial segments. The CI from the left ventricular blood pool adjacent to the segment was also measured in dB and subtracted from the CI(myo) (relative CI (RelCI)). RESULTS: CI had a logarithmic correlation and the calculated signal power a strong linear correlation with Levovist concentration in vitro. Thus, a difference in CI of X dB indicates a microbubble concentration ratio of 10(X/10). In normal control subjects, CI(myo) differed between the five segments (p < 0.0001), with a lower CI(myo) in deeper segments. However, RelCI did not differ significantly between segments (p = 0.083). RelCI was lower (p < 0.0001) in the 39 infarct segments (mean (SD) -18.6 (2.8) dB) than in the 55 normal segments (mean (SD) -15.1 (1.6) dB). RelCI differed more than CI(myo) between groups. CONCLUSIONS: The new quantitative method described can overcome the acoustic field inhomogeneity in evaluation of myocardial perfusion during MCE. RelCI represents the ratio of myocardium to blood microbubble concentrations and may correctly reflect myocardial blood volume fraction.

Effects of Ca2+ sensitizers on contraction, [Ca2+]i transient and myofilament Ca2+ sensitivity in diabetic rat myocardium: potential usefulness as inotropic agents.

The purpose of the present study was to investigate the effects of Ca2+ sensitizers EMD 57033, MCI-154, and EGIS-9377 in cardiac preparations from streptozotocin-induced diabetic rats. In enzymatically dissociated ventricular myocytes loaded with the Ca2+ probe indo 1, these Ca2+ sensitizers caused an increase in cell shortening without a significant effect on the intracellular Ca2+ ([Ca2+]i) transient. The contractile responses were substantially similar in myocytes from diabetic and age-matched control rats. In contrast, the contractile and [Ca2+]i responses to pimobendan and isoproterenol were significantly less in diabetic myocytes. The Ca2+ sensitivity of tension in beta-escin-skinned trabeculae from diabetic hearts was not significantly different from that of controls. The effect of EMD 57033 on myofilament responsiveness to Ca2+ was identical in control and diabetic preparations. The slower time course of relaxation observed in diabetic papillary muscles was further prolonged in the presence of EMD 57033. However, the extent of the increase in relaxation produced by EMD 57033 did not differ between control and diabetic muscles, and the detrimental effect on resting tension was less pronounced in the two groups. In anesthetized rats, echocardiography showed that intra-duodenal administration of EMD 57033 increased left ventricular systolic function without affecting variables of diastolic filling in both groups. Taken together, the present results suggest that Ca2+ sensitizers, unlike conventional inotropic agents, have the potential to increase in force of contraction to the same extent in nondiabetic and diabetic myocardium, possibly without exaggerating extremely the impairment of diastolic function in diabetes.

Clinical significance of noninvasive assessment of left ventricular diastolic function by Doppler echocardiography.

Transmitral flow velocity pattern obtained by the pulsed Doppler technique reflects left ventricular (LV) diastolic function, but an increase in left atrial pressure pseudonormalizes the flow pattern and masks diastolic dysfunction. We propose an index to assess LV diastolic function using color M-mode Doppler echocardiography and the base-line shift technique. This index, flow propagation velocity, represents the average velocity of early diastolic LV filling flow from the mitral orifice to mid-ventricle. In patients with ischemic heart disease and dilated cardiomyopathy including those with pseudonormalized transmitral flow pattern, flow propagation velocity had a good correlation with the time constant of early diastolic LV pressure decay (Tau), indicating that flow propagation velocity is a useful noninvasive parameter of diastolic function which does not pseudonormalize. We also found a significant correlation between flow propagation velocity and Tau in hypertrophic cardiomyopathy patients in contrast to inadequate or no correlation between each of the conventional parameters and Tau. In addition, our recent data suggest that flow propagation velocity was distinctly decreased even in the patients with hypertension who did not show significant increase in LV mass index. Flow propagation velocity is a unique noninvasive parameter of LV diastolic function, which can sensitively and accurately detect the diastolic impairment in patients with different types of cardiac diseases with various loading conditions.

Usefulness of early diastolic flow propagation velocity measured by color M-mode Doppler technique for the assessment of left ventricular diastolic function in patients with hypertrophic cardiomyopathy.

Flow propagation velocity (FPV) of left ventricular (LV) filling flow has been shown to be a useful index for the evaluation of LV diastolic function, which is relatively independent of preload in myocardial infarction and dilated cardiomyopathy, but the usefulness of FPV for hypertrophic cardiomyopathy (HCM) has not yet been determined. In 23 HCM patients and 26 control subjects, peak transmitral flow velocities in early diastole (E) and during atrial contraction (A), E/A ratio, deceleration time of E velocity, and isovolumic relaxation time were measured with the conventional Doppler technique, and FPV was measured from color M-mode Doppler images of LV filling flow. The time constant of LV isovolumic pressure decay (tau) was measured by a micro-manometer-tipped catheter in all HCM patients and 13 control subjects. Flow propagation velocity was significantly lower and deceleration time was significantly greater in HCM patients than in the control subjects, though no significant differences were observed in the other noninvasive indexes. Tau was significantly prolonged in HCM patients compared with that of control subjects (54+/-12 cm/s and 32 +/-7 cm/s, respectively; P<.0001). While the conventional indexes did not correlate with tau among the 36 patients in whom invasive studies were performed, FPV correlated well with tau (r = -0.76, P<.0001). Flow propagation velocity is a useful noninvasive index for the assessment of LV diastolic function in patients with HCM.

[Recent advances in echocardiographic diagnosis of ischemic heart disease].

Before the early 1990s, the diagnostic usefulness of echocardiography for ischemic heart disease had been relatively limited compared with that for other cardiac diseases such as valvular disease, congenital anomalies and cardiomyopathies. The principal role of echocardiography was to assess persistent regional wall motion abnormality as well as to detect complications of myocardial infarction. However, recent technological advances have created many newer applications of echocardiography in this field. One of the most important advances was seen in the field of stress echocardiography. Dobutamine stress echocardiography has become an established method of diagnosing transient myocardial ischemia due to coronary stenosis and assessing the myocardial viability of a persistently akinetic segment. More recently, several new contrast agents have been developed or will be available in the near future to visualize the blood stream within the left heart cavity and myocardial blood flow. Simultaneously, new ultrasound technologies including harmonic imaging and gated intermittent imaging have enhanced the selective visualization of contrast agents and will contribute to noninvasive imaging of coronary microcirculation. Harmonic imaging has also been shown to improve quality of B-mode image without a contrast agent and will play an important role in the clinical recognition of wall motion abnormality in patients with ischemic heart disease. Recent advances in three-dimensional technology have enabled accurate measurements of left ventricular volume and ejection fraction without any geometrical assumption, which may be especially important for the evaluation of ischemic patients who often have a deformed left ventricular cavity due to remodeling.

Enhanced GRK5 expression in the hearts of cardiomyopathic hamsters, J2N-k.

GTP binding protein-coupled receptor kinase 5 (GRK5) cDNA was cloned from the hearts of Syrian hamsters. The hamster GRK5 cDNA contained 1770 nucleotides encoding 590 amino acids, and the nucleotide sequence had 89.6% homology to the human homologue. An inbred cardiomyopathic hamster strain, J2N-k, was used to investigate the alteration of GRK5 mRNA expression in the setting of congestive heart failure. M-mode echocardiography revealed significant dilatation of the left ventricle and a decrease of left ventricular contractility in 20-week-old J2N-k hamsters compared with age-matched control hamsters, J2N-n. Semi-quantitative RT-PCR showed that GRK5 mRNA expression in the hearts of J2N-k was significantly higher than in those of J2N-n (J2N-k 60.3 +/- 13.3, J2N-n 25.8 +/- 17.2 arbitrary units, p < 0.005, n = 6 in each group). These results suggest that an enhanced GRK5 expression might play a role in the reduced responsiveness to catecholamines in failing hearts via beta-adrenergic receptor phosphorylation.

Beneficial effect of myocardial angiogenesis on cardiac remodeling process by amlodipine and MCI-154.

The present study examined the effect of long-term treatment with amlodipine and MCI-154 (a Ca2+ sensitizer) on progressive cardiac dysfunction and microvasculature in the dilated cardiomyopathic (DCM) hamster heart. After treatment of DCM hamsters (Bio 53.58) with amlodipine or MCI-154 for 15 wk from the age of 5 wk, amlodipine and MCI-154 were found to cause an increase in left ventricular percent fractional shortening and decreases in left ventricular diastolic dimension and isovolumic relaxation time in echocardiograms (P < 0.01). A hemodynamic study showed that the diastolic time constant decreased in the amlodipine-treatment group (P < 0.05). In a morphometric study employing a double-staining method that discriminated arteriolar and venular capillaries, amlodipine and MCI-154 caused increases in total capillary density (P < 0.05) and the proportion of venular capillaries (P < 0.05). Moreover, Northern blot analysis showed that the expression of mRNA for vascular endothelial growth factor was significantly increased by amlodipine and MCI-154. They preserve coronary microvasculature in the DCM hamster and might induce angiogenesis of small vessels, thereby contributing to preservation of cardiac systolic and diastolic function.

Chronic effects of enalapril and amlodipine on cardiac remodeling in cardiomyopathic hamster hearts.

This study examined the effects of long-term treatments with the angiotensin-converting enzyme inhibitor, enalapril, and the calcium antagonist, amlodipine, on the morphologic changes, progressive left ventricular dysfunction, and gene expression of the ryanodine receptor (RyR) and phospholamban (PLN) in dilated cardiomyopathy. From the ages of 5 through 20 weeks, dilated cardiomyopathic hamsters, BIO53.58 (BIO), and control hamsters, F1b, orally received either enalapril or amlodipine. Cardiac function was assessed by echocardiography. At the age of 20 weeks, the collagen volume fractions were analyzed by the stereologic method. RyR and PLN messenger RNAs (mRNAs) were examined by Northern blot in the amlodipine group. In BIO, the reduction of left ventricular percentage of fractional shortening was attenuated in the enalapril group (p < 0.05) and amlodipine group (p < 0.001), and the increase in the collagen volume fraction and the loss of myocytes were suppressed in the amlodipine group compared with the untreated group. RyR mRNA level decreased in BIO (p < 0.01) compared with F1b, but PLN mRNA level was unchanged. RyR and PLN mRNA levels were unaffected by the treatment with amlodipine. Enalapril and amlodipine prevent progressive remodeling and reduce cardiac dysfunction in BIO. Amlodipine prevents fibrosis and cell death without modifying RyR and PLN mRNA levels in BIO.

Angiotensinogen gene polymorphism in Japanese patients with hypertrophic cardiomyopathy.

To examine the contribution of the renin-angiotensin system to hypertrophic cardiomyopathy (HCM), we studied 96 patients with HCM (mean age 50 years, 55% male), 105 of their unaffected siblings and offspring, and 160 healthy subjects without known hypertension and left ventricular hypertrophy (LVH) who were frequency matched to cases by age and sex. Patients were divided into familial or sporadic HCM (FHCM or SHCM) groups with or without affected members of their family. The region of interest in the angiotensinogen (AGT) gene, the missense mutation with methione-to-threonine amino acid substitution at codon 235 in angiotensinogen (M235T), was amplified by polymerase chain reaction with the use of allele-specific oligonucleotide primers flanking the polymorphic region of the AGT gene to amplify template deoxyribonucleic acid prepared from peripheral leukocytes. The T allele frequency was higher in the SHCM group than in unaffected siblings and offspring (88% vs 78%, X2 = 4.6, p < 0.05). The M allele frequency was higher in unaffected siblings and offspring than in patients with SHCM (23% vs 12%, X2 = 4.6, p < 0.05). The T allele frequency among unaffected siblings and offspring was similar to that observed in healthy subjects (78% vs 78%). We conclude that HCM, especially in sporadic cases, is partially determined by genetic disposition. The molecular variant of angiotensinogen T235 seems to be a predisposing factor for cardiac hypertrophy in HCM and carries an approximately twofold increased risk.

[Intraoperative and follow-up color Doppler echocardiography for evaluating the surgical results of aortic valvuloplasty in a patient with bicuspid aortic valve].

A 21-year-old man underwent aortic valvuloplasty for aortic regurgitation due to bicuspid aortic valve. After the initial procedure for valvuloplasty of the anterior cusp, transesophageal color Doppler flow imaging revealed a significant regurgitant jet directed posteriorly as observed preoperatively. After an additional valvuloplastic procedure for the anterior cusp, the size of the regurgitant signal was reduced and directed to the center of left ventricular outflow tract. The surgery was then completed. On the 5th postoperative day, an aortic regurgitant murmur reappeared and color Doppler echocardiography showed a mild but significant regurgitant jet directed toward the interventricular septum, which may have been due to contraction of the anterior cusp treated by valvuloplasty. Aggravation of the aortic regurgitation in the early stage after plastic surgery is important and requires consideration in the intraoperative assessment.

A new approach for evaluation of left ventricular diastolic function: spatial and temporal analysis of left ventricular filling flow propagation by color M-mode Doppler echocardiography.

OBJECTIVES: To evaluate left ventricular diastolic function and differentiate the pseudonormalized transmitral flow pattern from the normal pattern, the propagation of left ventricular early filling flow was assessed quantitatively using color M-mode Doppler echocardiography. BACKGROUND: Because the propagation of left ventricular early filling flow is disturbed in the left ventricle with impaired relaxation, quantification of such alterations should provide useful indexes for the evaluation of left ventricular diastolic function. METHODS: Study subjects were classified into three groups according to the ratio of early to late transmitral flow velocity (E/A ratio) and left ventricular ejection fraction: 29 subjects with an ejection fraction > or = 60% (control group); 34 with an ejection fraction < 60% and E/A ratio < 1 (group I); and 25 with ejection fraction < 60% and E/A ratio > or = 1 (group II). The propagation of peak early filling flow was visualized by changing the first aliasing limit of the color Doppler signals. The rate of propagation of peak early filling flow velocity was defined as the distance/time ratio between two sampling points: the point of the maximal velocity around the mitral orifice and the point in the mid-left ventricle at which the velocity decreased to 70% of its initial value. High fidelity manometer-tipped measurement was performed in 40 randomly selected subjects. RESULTS: The rate of propagation decreased in groups I and II compared with that in the control group (33.8 +/- 13.8 [mean +/- SD] and 30.0 +/- 8.6 vs. 74.3 +/- 17.4 cm/s, p < 0.001, respectively) and correlated inversely with the time constant of left ventricular isovolumetric relaxation and the minimal first derivative of left ventricular pressure (peak negative dP/dt) (r = 0.82 and r = 0.72, respectively). CONCLUSIONS: Spatial and temporal analysis of filling flow propagation by color M-mode Doppler echocardiography was free of pseudonormalization and correlated well with the invasive variables of left ventricular relaxation.

Enhanced expression of beta-adrenergic receptor kinase 1 in the hearts of cardiomyopathic Syrian hamsters, BIO53.58.

We cloned an entire encoding sequence of beta-adrenergic receptor kinase 1 (beta ARK1) cDNA from the hearts of Syrian hamsters through reverse transcription and subsequent polymerase chain reaction. The cloned cDNA contained 2067 nucleotides coding 689 amino acids. The sequence had 95% homology to rat beta ARK1 and 90% homology to human homologue. Cardiomyopathic Syrian hamster, BIO53.58, has been used as a model animal of congestive heart failure. M-mode echocardiography confirmed that left ventricular contractility of 20-week-old BIO53.58 was markedly reduced. The expression of beta ARK1 mRNA in the hearts of BIO53.58 was significantly increased compared to control hamsters, F1b, suggesting that the enhanced beta ARK1 expression is acting as a negative feedback mechanism in order to maintain intracellular homeostasis against accelerated stimulation by catecholamines via phosphorylation of beta-adrenergic receptor.

[Evaluation of valvular lesions by three-dimensional echocardiography].

A recently developed, on-line image processing system (Tomtec EchoScan) for three-dimensional (3D) echocardiography was compared with conventional two-dimensional examination and our own off-line 3D system. Transesophageal echocardiography was performed in 10 cardiac patients using an omniplane transducer which was automatically rotated under the control of the 3D system. At each angle of the transducer, the respiration-gated image of one cardiac cycle was acquired and transferred into the computer, where the dynamic 3D images of mitral and/or aortic valve were reconstructed. The EchoScan system enabled 3D recognition of the structural and dynamic abnormalities of the valves, such as mitral valve prolapse, although tissue information, which is expressed as a gray scale in the conventional echocardiography, cannot be evaluated from the 3D image. Average times were 5.4 min for the data acquisition, 11.8 min for the 3D processing and 5.7 min for the rendering. Although it seems necessary to improve the efficacy of data acquisition, to shorten the calculation time and to minimize the artifacts, this system enables assessment of 3D cardiac structures at the bedside and to fully recognize valvular lesions preoperatively in patients with valvular heart disease.

Angiotensin-converting enzyme gene polymorphism in Japanese patients with hypertrophic cardiomyopathy.

To examine the contribution of the angiotensin-converting enzyme (ACE) gene to hypertrophic cardiomyopathy (HCM), we determined the ACE insertion/deletion (I/D) polymorphism in 80 patients with HCM and 88 of their unaffected siblings and children. Patients were divided into familial or solitary HCM (FHCM or SHCM) groups with or without affected family members. Genotypes were identified by the polymerase chain reaction (PCR) with oligonucleotide primers flanking the polymorphic region in intron 16 of the ACE gene to amplify template DNA prepared from peripheral leukocytes. D-allele frequencies were 0.38 in all subjects, 0.42 in patients with HCM, and 0.35 in relatives (p < 0.05). The probability ratios were 1.98, 1.46, and 2.97 in patients with HCM, FHCM, and SHCM, respectively. The D allele frequency was higher in SHCM than in FHCM (p < 0.05). The findings suggest that HCM, especially in solitary cases, is partially determined by genetic disposition. Findings imply that the ACE D allele is one of the genetic contributing factors associated with cardiac hypertrophy in HCM.

Urinary 1-hydroxypyrene as a marker of exposure to polycyclic aromatic hydrocarbons in environment.

The concentrations of pollutants, especially polycyclic aromatic hydrocarbons (PAHs), originating from automobile emissions are high in areas around urban arterial roads. To investigate the possibility of using urinary 1-hydroxypyrene (1-POH) a metabolite of pyrene, as a marker for estimating the amount of human exposure to PAHs, both an animal experiment and an ecological correlation study were conducted. Rats were exposed to one of two sources of PAH: diesel engine emissions containing particulate matter and NO2 at average concentrations of 4.20 mg/m3 and 2.90 ppm, respectively, or, for the control group, air having the respective average concentrations of 0.01 mg/m3 and 0.02 ppm. The concentration of pyrene was 36 ng/mg in the particulate matter in the diluted diesel engine exhaust and 9.0 ng/g in the feed to the rats. Urinary 1-POH levels in the rats of the exposure group increased remarkably over those of the control group, 2.4 times as much by the 2nd week of exposure and 5.6 times by the 4th and 8th weeks. The ecological correlation study was conducted in 1988 and 1989 in two area of Tokyo along arterial roads (Meguro and Itabashi Wards) and in one suburban area (Higashiyamato City) to measure urinary 1-POH levels in elementary school children who lived in those areas. Urinary samples were collected in October in 1988, as well as in January, May, and July in 1989. Throughout the period of investigation, the schoolchildren in the highly NOx-polluted Meguro and Itabashi Wards showed significantly higher urinary 1-POH levels than the children in the less-polluted Higashiyamato City by a factor of 1.1-1.6. These results suggest that the urinary 1-POH level could be used as a good marker for estimating the amount of exposure of residents to PAHs.

[Diagnosis of prosthetic mitral valve regurgitation by Doppler color flow imaging using right parasternal approach: a comparative study with transesophageal method].

Doppler color flow imaging is a useful tool in evaluating mitral regurgitation (MR). However, it is frequently difficult to assess prosthetic valve MR by the conventional transthoracic approach using left parasternal or apical echo-windows, because of the interception of ultrasound by the prosthesis or artifacts produced by its motion. The purpose of this study is to determine the usefulness of the "right" parasternal approach (RPA) in the echo diagnosis of prosthetic MR. Six patients with pathological prosthetic MR determined by transesophageal approach (TEA) were studied. Transthoracic echo was performed using both the RPA and the conventional approach, and the presence or absence and the extent of MR signals by these transthoracic approaches were compared with those by TEA. Prosthetic MR was detected in five of six patients by the RPA and the extent of MR signals by the RPA was very similar to that by TEE in each of the five patients. MR could not be detected by the RPA only in one patient, whose MR was estimated to be very mild by TEE. By the conventional approach, MR could not be detected in three patients and the degree of MR was significantly underestimated in two of the remaining three patients. Thus, the transthoracic RPA is often as useful as TEA in diagnosing prosthetic MR, which is often undetectable or underestimated by the conventional approach. Because the RPA is less invasive than TEA, the RPA should be encouraged in patients with suspected prosthetic mitral valve dysfunction.

[A case of cardiac myxoma associated with congenital oculocutaneous albinism].

This case is a 43 year-old-woman of left atrial myxoma associated with oculocutaneous albinism, who was admitted to our hospital because of nocturnal cough everyday. Electrocardiogram showed normal sinus rhythm and complete right bundle branch block. Chest X-ray disclosed slight enlargement of left atrium. Echocardiography revealed the left atrial pedunculated tumor, arising from atrial septum, prolapsing into left ventricle during diastole, which was coincided with lucent tumor by levophase of pulmonary arteriography. Feeder artery of this tumor was visualized by right coronary arteriography. Cardiac catheterization represented normal pressure of right-sided heart. Thus the diagnosis of left atrial myxoma was established. At the operation, radical excision of the base of tumor and septum and patch closure was undergone. The gross morphology and microscopic findings were consistent with myxoma.