Akira Kitabatake

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

OBJECTIVESnTo 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.nnnBACKGROUNDnBecause 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.nnnMETHODSnStudy 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.nnnRESULTSnThe 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).nnnCONCLUSIONSnSpatial 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.

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.

Renin-Angiotensin System in Failing Heart

Extrahepatic synthesis and localization of angiotensinogen have been described in animals, thus establishing the tissue renin-angiotensin system. We examined angiotensinogen messenger RNA synthesis by northern blotting. It was detected not only in the liver, but also in both the atrial and ventricular heart tissues, suggesting that angiotensinogen is synthesized in the human heart. Immunohistochemical studies using a specific antibody to angiotensinogen revealed a stronger reaction in the endocardial layer of the human left ventricle, than in the epicardial layer, and intense immunoreactivity in the conduction system and right atrium. Furthermore, our experiments revealed a widespread immunopositive reaction for angiotensinogen in the left ventricle of diseased hearts. We examined the participation of the collagen in the occurrence and progression of cardiomyopathy. The acetic acid solubility of collagen and reducible crosslink decreased in cardiomyopathic hamsters as the fibrosis progressed, but was unchanged in controls. These findings indicate that in the early phase of cardiomyopathy the extracellular matrix of the myocardium is similar to immature tissues. In the later phase, the matrix resembles that of hard tissues, and is insoluble. Furthermore, we examined the relationship between angiotensin II and collagen synthesis. Basal collagen synthesis in cardiac fibroblasts from spontaneously hypertensive rats was 1.6-fold greater than that in Wistar-Kyoto rats. The responsiveness of collagen production to Ang II was significantly enhanced in SHR. This effect was angiotensin receptor-specific, because it was blocked by the competitive inhibitor. These results indicate angiotensin II may play an important role in collagen accumulation in hypertensive cardiac hypertrophy.

Expression of renin and angiotensin-converting enzyme in human hearts

SummaryTo understand the significance of the tissue renin-angiotensin system in the heart, we examined the expression of renin and angiotensin-converting enzyme (ACE) in autopsied human hearts. Samples were taken from organs obtained at autopsy from 15 patients without heart disease and 3 patients with heart disease (old myocardial infarctions, acute myocardial infarctions, and hypertrophic cardiomyopathy). We examined the expression of renin and ACE mRNA by using the reverse transcription-polymerase chain reaction (RT-PCR). RT-PCR showed the expression of renin in the right atria in all patients. However, expression of renin mRNA in the left ventricles was not found in any of the 15 hearts without heart disease. In contrast, renin mRNA was detected in the left ventricles in hearts with heart disease. ACE mRNA was detected in both the atria and the ventricles in normal hearts, and its expression did not alter in diseased hearts. These findings suggest that renin mRNA is expressed mainly in the right atria in normal hearts, but that is expression in the left ventricle can be activated in some pathological conditions.

Distribution of angiotensinogen in diseased human hearts

Extrahepatic synthesis and localization of angiotensinogen (ATN) have been described in animals, thus establishing the tissue renin-angiotensin (RA) system. However, there had been no reports of tissue RA systems in human organs, including the heart. In earlier, we have reported the possibility of ATN synthesis in the human heart using ribonuclease protection assay system. ATN mRNA was detected not only in the liver, but also in both the atrial and ventricular heart tissues, suggesting that ATN is synthesized in the human heart. In this report, we looked for the distribution of ATN in diseased human heart.Northern blot hybridization of cDNA with total RNA extracted from human liver, brain, kidney, atrial and ventricular tissues revealed that ATN mRNA exists in cardiac ventricule.Immunohistochemical studies using a specific antibody to ATN revealed a stronger reaction in the endocardial layer of the human left ventricle, than in the epicardial layer, and intense immunoreactivity in the conduction system and right atrium. This distribution pattern was similar to that of human atrial natriuretic peptide (hANP), which functions a smooth muscle relaxant. Double immunostaining of ATN and hANP demonstrated that all myocytes in the right atrium had immunopositive reactions to ATN, hANP or both of ATN and hANP. Double immunoelectron staining enabled us to show more detailed localization of ATN and hANP; hANP only existed in the specific granules and ATN existed in the myofibril, but not in the granule. Furthermore, our experiments provide evidence of ATN in healthy human hearts and also reveal a widespread immunopositive reaction for ATN in the left ventricle of diseased hearts.

Alteration of extracellular matrix in dilated cardiomyopathic hamster heart.

The purpose of this study was to characterize the collagen in hereditary dilated cardiomyopathic hamster hearts, and to examine the participation of the collagen in the occurrence and progression of cardiomyopathy.BIO 53.58 hamsters (5, 10, 20 weeks old) were used as the model of dilated cardiomyopathy. Flb hamsters were used as controls. The collagen content was almost constant at any age in the Flb hamsters, but increased with age in BIO 53.58 hamsters. Type III collagen increased significantly in BIO 53.58 hamsters at 10 weeks. The acetic acid solubility of collagen decreased in BIO 53.58 hamsters as the fibrosis progressed, but was unchanged in controls. Reducible crosslinks showed a tendency to decrease progressively in BIO 53.58 hamsters. There were no differences between Flb and BIO 53.58 hamsters at 5 weeks, but its expression in BIO 53.58 hamsters at 10 and 20 weeks of age increased compared to Flb controls.These findings indicate that in the early phase of cardiomyopathy the extracellular matrix of the myocardium is rich in type III collagen. In the later phase, the matrix resembles that of hard tissues, whose collagen is mainly of type I collagen and is insoluble. These data suggest that the increased collagen synthesis may impair the cardiac function in the development of cardiomyopathy.

Three-Dimensional Display of Human Heart Motion Using Medical Ultrasonic Images

In this paper we report a method for displaying mitral valve motion of a beating heart in a three-dimensional (3-D) image reconstructed from twenty-eight different scanning plane tomograms, each of which consists of twenty successive ultrasonic B-mode images. A 3-D image consists of surface polygon sets to separate the internal and external regions of the heart. The 3-D image is smooth with lighting calculated from vertex normals of polygons. The 3-D mitral valve motion image is obtained from repeated 3-D images in phase in one cardiac cycle. In addition, we display stereoscopic heart images which have angular viewing separation for viewing images, and we obtain spatial relationships of heart anatomy from such images.

Neurofibromatosis complicated with XXX syndrome and renovascular hypertension

A 25‐year‐old woman with neurofibromatosis was admitted to our hospital for evaluation of hypertension. When she was 6 years old, she was diagnosed as having neurofibromatosis and XXX syndrome because of multiple café‐au‐lait spots, neurofibromas of the skin and mental retardation. Chromosome analysis revealed that her karyotype was 46, XX/47, XXX. Renal arteriography disclosed aneurysmal change and stenosis of the right renal artery. After right‐side nephrectomy and aneurysmectomy, the kidney was autotransplanted in the left iliac fossa. Surgical procedure resulted in marked amelioration of the hypertension without medical treatment. Thus, aortorenal bypass and renal autotransplantation have emerged as the preferred revascularization operations. This is the first report of a chromosomal linkage between neurofibromatosis which is thought to be an autosomal dominant disease and the XXX syndrome.

3-D Motion Image Reconstruction Using Volume Rendering Technique from Ultrasound Echographic Images

Recently, use of 3D and 4D volume visualization from X-ray CT and 11RI images has increased in many fields[l]. Realtime image generation is one of the advantage of acoustical method to MRI and X-ray CT techniques. 1Iany ultrasound echographic devices can visualize sliced sections of moving organs in realtime. By gathering image slices to cover certain volume space and time intervaL a space-time volume dataset or 4D volume dataset can be constructed. Volume visualization techniques can be applied to the dataset to create photo-realistic images and it is also possible to make a movie by assembling them.