A decline is usually observed in the myocardial uptake of thallium-201 in delayed imaging compared with initial imaging. In patients with severe coronary artery disease (CAD), the uptake is sometimes higher in the delayed than in the initial imaging, which is expressed as negative washout rate. To evaluate the diagnostic implications of this negative washout rate the findings of dipyridamole thallium scintigraphy in 582 patients with coronary artery disease were evaluated. The negative washout rate was present in 201 of 582 patients (35%). It had a significant association with high grade coronary artery narrowing of ≥90%. Sensitivity in detecting patients with this high grade narrowing by negative washout rate was 48%, its specificity was 93%, and its positive predictive value was 94%. Sensitivity to detect individual coronary artery narrowing of ≥90% did not decrease according to the extent of CAD, with the highest detection in the left anterior descending coronary artery and the lowest in the left circumflex coronary artery. Since patients with high grade coronary narrowing often require coronary intervention, the results of this study suggest the diagnostic importance of negative washout rate in the identification of the particular subset of patients with CAD.

抄録全体を表示

In order to evaluate the usefulness of echocardiography in detection and characterization of pulmonary arterial hypertension (PAH) in scleroderma patients, we performed M-mode, two-dimensional, and Doppler echocardiography in 71 patients with progressive systemic sclerosis (PSS) and related syndromes: mixed connective tissue disease (MCTD) and overlap syndromes. We estimated systolic pressure gradients across the tricuspid valve from the peak velocity of tricuspid regurgitation (TR) by color-flow guided continuous wave Doppler. TR velocities of analyzable quality for gradient estimation were obtained in 28 patients (39%), of whom 12 showed PAH (peak TR velocity≥2.5 m/sec). In comparison, analyzable TR was recorded in 19 (35%) of 55 patients with left-sided cardiac disease. None of the 12 with Doppler-estimated PAH showed left ventricular dilatation or decreased fractional shortening by M-mode and two-dimensional measurements. Nonsimultaneous cardiac catheterization con-firmed PAH in 8 of 9 with Doppler-estimated PAH and in 3 of 12 without analyzable TR who had hemodynamic study. Doppler-estimated right ventricular systolic pressures (RVSP) correlated well with catheterization-measured pulmonary arterial systolic pressures (PASP) (<0.01). Our results indicate that Doppler echocardiography is useful in detecting subclinical PAH and estimating PASP in patients with collagen vascular disease. The results of pulmonary function studies suggest that PAH in MCTD is mainly caused by pulmonary vasculopathy.

抄録全体を表示

The pulmonary blood distribution was examined in 17 patients with tetralogy of Fallot (TOF) pre and postoperatively with macroaggregates of ^99mTc-labeled human serum albumin. Most of the patients with TOF demonstrated an abnormal preoperative distribution pattern. The abnormalities included not only an unbalanced distribution between the right and left lungs but also a maldistribution of peripheral vessels in each lung. The Right/Left lung counts ratio and Pulmonary Peripheral Index (calculated in order to express the severity of peripheral maldistribution) correlated neither to the diameter nor the cross-sectional area of either right or left pulmonary arteries which were measured angiographically. Postoperatively, the pulmonary blood was shunted toward the developed side of the lung which further contributed to maldistribution of blood flow and unbalanced pulmonary growth. Since the patients with an unbalanced pulmonary blood distribution demonstrated a higher right ventricular pressure one year after the operation, a palliative operation facilitating the growth of the underdeveloped side of the lung might be considered as an effective procedure to precede intracardiac repair.

抄録全体を表示

In order to evaluate the effect of acute hypoxia on left ventricular (LV) contractility and diastolic function, hemodynamics and LV wall motion were investigated in anesthetized open-chest paced dogs using M-mode or pulsed Doppler echocardiography. Animals were ventilated with 10% oxygen (Hypo 1) and 6.3% oxygen (Hypo 2). LV contractility and diastolic functions were enhanced under "Hypo 1" and at an early phase of "Hypo 2". However, LV functions, both systolic and diastolic, were simultaneously reduced in the presence of hypercapnic acidosrs by "Hypo 2". Peak velocities of diastolic rapid filling flow (R) and atrial contraction flow (A) were increased under "Hypo 1", but showed a biphasic change (an increase and a subsequent decrease) under "Hypo 2". The ratio of A/R, known as an index of LV diastolic function, was not altered under hypoxia alone or even under hypercapnic acidosis. Even when hypoxia seems to enhance LV contractility, LV function has already begun to be de-pressed with a reduction of pH. This seems, however, to be compensated for by LV dilatation and increase in preload, or preservation of left atrial performance.

抄録全体を表示

We examined the electrophysiologic changes before an onset of ventricular tachyarrhythmia during partial reperfusion following severe myocardial ischemia. The left anterior descending coronary artery was occluded and cannulated below the occluded portion in 26 dogs. To deplete collateral flow into the ischemic myocardium, retrograde blood flow was induced for 20 min. Then, in all dogs except 7 with ventricular fibrillation during retrograde blood flow, partial reperfusion through collateral flow into the ischemic myocardium was produced by stopping the retrograde flow. Within 2 min of partial reperfusion, sustained ventricular tachycardia (VT) occurred in 7 dogs (group A) and non-sustained VT degenerating ventricular fibrillation occurred in 11 dogs (group B) of the remaining 12 dogs. In 6 dogs of group A and 9 of group B, epicardial conduction block appeared 5.0±2.2 and 3.5±1.3 min after ischemia. This was followed by fractionated electrical activities 15.2±3.2 and 11.7±3.3 min after ischemia. In group A, the fractionation had a slight change in configuration and a small increase in amplitude before the onset of VT during reperfusion; in group B, new deflections with large amplitude emerged before it. There was a significant difference in the amplitude (0.38±0.2 vs 0.67±0.3 mV, p<0.025) between the 2 groups, although there was no significant difference in the amplitude (0.33±0.2 vs 0.23±0.1 mV) of the fractionation just before reperfusion. Our results show that slight improvement in fractionation induces sustained VT, and new deflections induce non-sustained VT degenerating ventricular fibrillation, even during partial reperfusion.

抄録全体を表示

A patient is reported in whom exercise induced reversible ischemic left anterior fascicular block and far advanced right bundle branch block. Master's two step exercise test for pre-operative check-up revealed significant ST elevation in leads V1-5, negative U waves in leads V3-5 and fascicualr blocks with retrosternal anginal chest pain. Long acting nitrate and nicorandil relieved the fascicular blocks.

抄録全体を表示

We studied three women with the long QT syndrome. They were aged 42, 52 and 25 years and had experienced recurrent syncopal attacks. We followed case 1 for 17, case 2 for 18, and case 3 for over 6 y. The attacks tended to occur during the premenstrual stage in case 1 and case 2; case 3 often experienced attacks after exercise. The QT(U)c intervals on admission were 0.68, 0.62, and 0.50 in case 1, 2, and 3, respectively. Torsade de pointes followed by ventricular fibrillation was documented in case 1 and case 2. Although each was treated with a beta-blocker, none was fully compliant with the regimen. In case 1, estrogen therapy administered to maintain the hormonal balance premenstrually effectively prevented attacks. Despite the inconsistent use of beta-blockers, the attacks in case 1 and case 2 tended to decrease with age. Case 2 experienced no attacks after menopause. Cause 3 took medication consistently and remained free of attacks for over 6 y. Although she discontinued beta-blocker therapy because of pregnancy, she has experienced no attacks to date. These case studies suggest that hormonal status may be important in the development of syn-copal attacks in female patients with the long QT syndrome.

抄録全体を表示

Emergency aortic valve replacement with double aorto-coronary bypass surgery was performed to treat severe intractable congestive heart failure in an 82-year-old man. Mild circumflex and left anterior descending artery lesions were present and the pressure gradient across the aortic valve was 80 mmHg despite a low cardiac output. The preoperative anteroseptal akinesia seen by two-dimensional echocardiography was normalized after surgery. Thus, even in patients with segmental left ventricular dyfunction, tight aortic stenosis might be present when concomitant mild ischemic heart disease is present.

抄録全体を表示

We demonstrated that phosphatidylinositide-specific phospholipase C (PLC) activity was greater in cardiomyopathic hamster hearts (BIO 14.6 and BIO 53.58) then in hamster controls (F1b). Inositol trisphosphate (IP₃) production was markedly greater in both of the cardiomyopathic hamsters, BIO 14.6 and BIO 53.58. We have also determined the sarcoplasmic reticulum (SR) function of heart. Calcium uptake into SR markedly increased in BIO 14.6. On the other hand, it significantly decreased in BIO 53.58 compared with F1b. It is well known that IP₃ stimulates calcium release from SR. In BIO 14.6, calcium relrease from SR stimulated by IP₃ increased, but its effect decreased in BIO 53.58 compared with F1b. These results suggest that PI response may produce high intracellular calcium levels in both BIO 14.6 and BIO 53.58 myocytes. In addition, in the BIO 53.58 hamster the sarcoplasmic reticulum deteriorate in function. It was concluded from these results that a prolonged high intracellular calcium level may lead to the death of BIO 53.58 myocytes. The expression of angiotensinogen mRNA was observed in the hamster heart. There was no differences in its expression level between F1b, BIO 14.6 and BIO 53.58. There was no effect of ages on its expression in these hamster hearts. We have also determined the distribution of angiotensinogen in these hamsters. At 4 weeks of age, the immunohistochemical study revealed that angiotensinogen was widely distributed in subendcardium in these hamsters. There was no difference in its distribution between F1b, BIO 14.6 and BIO 53.58. But at 20 weeks old of age its immunoreactivity decreased in BIO 53.58. There was no effect of age on its reactivity in F1b and BIO 14.6. We have detected angiotensinogen in heart, but its role is still not clear. A further study should be done to clarify its role in cardiac hypertrophy and cell damage.

抄録全体を表示

Deletions and point mutations of mitochondrial DNA (mtDNA) of patients with dilated or hypertrophic cardiomyopathy were analyzed using the polymerase chain reaction and fluorescence-based direct sequencing. The patients included are with hypertrophic cardiomyopathy associated with left ventricular dilatation, a patient with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and a patient with fatal infantile cardiomyopathy. Deletions were frequently seen in mtDNA in patients with dilated cardiomyopathy. The mtDNA was sequenced and the direct repeat at each edge of deletion was identified as (5'-CATCAACAACCG-3') which was located in the ATPase6 gene and in the D-loop region. In a patient with hypertrophic cardiomyopathy associated with left ventricular dilatation, another mutant mtDNA was found not to have directly repeated sequence, and was revealed to jump from nucleotide position 8, 992 to position 16, 072 of mtDNA resulting in a 7, 079 bp deletion. This patient had unique point mutation in the tRNA genes. A G-to-A transition in the tRNA^Cys gene (nucleotide position 5, 821) at the aminoacyl acceptor stem and an A-to-G transition in the tRNA^Thr gene (nucleotide position 15, 951) were identified. In a patient with MELAS, an A-to-G transition in the tRNA^Leu(UUR) gene (nucleotide position 3, 243) was observed. This mutation was located at the 5' end of the dihydrouridine loop of this tRNA molecule, and would disturb its function. In a patient with hypertrophic cardiomyopathy associated with lactic acidosis, mutations of mtDNA should be suspected. In a patient with fatal infantile cardiomyopathy, three point mutations in the genes of tRNA^Leu (nucleotide position 3, 254), tRNA^Ile (nucleotide position 4, 317), and tRNA^Trp (nucleotide position 5, 554) were identified. From these data, it is suggested that mtDNA deletions and point mutations which induce base substitutions in protein subunit genes, and base substitutions in tRNA genes which affect the function of the mitochondrial respiratory chain are important contributory factors to the genesis of some forms of cardiomyopathy.

抄録全体を表示

To identify genetic factors in the immune system which control the susceptibility to dilated cardiomyopathy (DCM), HLA class II DNA typing was performed in 61 Japanese patients, using PCR/SSO probe analyses. The frequencies of HLA-DQB1^*0503 (15% vs 5%; RR=3.06, χ²=7.19) and DQB1^*0604 (21% vs 10%; RR=2 41 χ²=6.20) were significantly increased and that of HLA-DQB1^*0502 (RR=1.74) was slightly increased in the DCM patients. The frequency of DQB1^*0303 (16% vs 31%; RR=0.44, χ²=5.16) was significantly decreased in the patients. The increased HLA-DQB1 alleles have a histidine residue in common at the 30th codon for the HLA-DQβ chain. Among the genetic markers studied by Southern blot analyses, IGLV (immunoglobulin lambda light chain, pV3.3) showed a strong association with DCM, i.e. A2/A2 genotype was found in 37.7% of patients whereas it was observed in only 18.9% of the control subjects (RR=2.6, χ²=7.77). The frequency of this genotype was higher in patients under age 45 years at the time of diagnosis (45.5%, RR=3.6, χ²=10.02). These results suggest that HLA and immunoglobulin genes are closely linked to susceptibility to DCM.

抄録全体を表示

Cell-mediated autoimmunity has been strongly implicated in the pathogenesis of the myocardial cell damage involved in viral myocarditis. To investigate the cellular and molecular bases of both target cells and effector cells for cell-mediated cytotoxicity involved in viral myocarditis and dilated cardiomyopathy, we first examined the expression of major histocompatibility complex (MHC) antigens and a cell adhesion molecule, intercellular adhesion molecule-1 (ICAM-1) in myocardial cells of a murine model of viral myocarditis and in patients with acute myocarditis and dilated cardiomyopathy. Secondly, we analyzed the characteristics of the infiltrating cells in the heart, especially the expression of a cytolytic factor, perforin. We found that Coxsackievirus B3 (CVB3)-induced murine acute myocarditis resulted in enhanced expression of MHC (class I) antigens and ICAM-1 on myocardial cells, and that perforin was abundantly expressed in NK (natural killer)-like large granular lymphocytes (LGL), which represent the main infiltrating cell type in the early stage. Immunoelectron microscopic study showed killer cells directly damaging cardiac myocytes by the release of perforin. Perforin was also expressed in the infiltrating cells in the heart of a patient with acute myocarditis. Both MHC antigens and ICAM-1 were clearly expressed in the hearts of patients with acute myocarditis and dilated cardiomyopathy. These data provided direct evidence that cell-mediated cytotoxicity plays a critical role in the myocardial cell damage involved in viral myocarditis.

抄録全体を表示

The question of whether the etiology of DCM is immune or autoimmune has been increasingly discussed. Abnormal findings on humoral immunity in DCM were investigated, especially those regarding anti-heart antibodies (AHA), IgG subclasses and soluble interleukin-2 receptor (slL-2R). The heterophile type AHA was detected in 64.7% of cases by the indirect immunofluorescence technique (IF) with rat heart, by indirect IF with human heart AHA in 57.8% of cases, and by thin-layer chromatogram with human glycolipids AHA in 44% of cases. Also, 57.1% of the specimens were found to bind IgG on perimyocytes by direct IF with biopsy specimens taken from patients with DCM. The epitope of an antigen which reacted with the heterophile type AHA is a Gal α 1-3Gal structure. 200 Kd, 70 Kd and 40 Kd antigens were reacted with AHA detected by indirect IF with human heart. The possible mechanisms of AHA in the pathogenesis could be either complement dependent cytotoxicity or interference to cardiac metabolism. The concentration of SIL-2R and IgG3 in sera from patients with DCM were elevated. These results suggest that immunological abnormalities occur continuously in DCM.

抄録全体を表示

We examined myocardial tissues for the presence of enteroviral RNA in animal models with experimental coxsackievirus B₃ myocarditis and in endomyocardial biopsy samples obtained from patients clinically diagnosed as having dilated cardiomyopathy or myocarditis using polymerase chain reaction (PCR) gene amplification with enterovirus-generic primers and/or coxsackievirus B3-specific primers. In animal models, coxsackievirus B3 was detected in myocardial tissues up to 28 days, 56 days and 180 days after inoculation, in C3H/He mice. A/J mice and Syrian golden hamsters, respectively. The viral genomes were identified by in situ hybridization in myocardial cells and some interstitial cells in and around the myocarditic lesions in animals. In human endomyocardial biopsy samples, enteroviral RNA sequences were detected in 8 (32%) out of 25 patients with clinical dilated cardiomyopathy and in 3 (33%) out of 9 patients with clinical myocarditis. The patients showing histologic findings of myocarditis and clinical features resembling dilated cardiomyopathy had a high incidence (83%) of positive PCR result for enteroviral RNA sequences. Additionally, 25% of patients with dilated cardiomyopathy showing no histologic findings of myocar-ditis had positive PCR result. This study supports a link between viral myocar-ditis and dilated cardiomyopathy.

抄録全体を表示