To examine the prognostic role of the circulating soluble form of Fas (sFas), circulating sFas levels were measured in 33 patients with dilated cardiomyopathy (DCM) and 12 age-matched normal control subjects (NC) using an enzyme-linked immunosorbent assay (ELISA). Circulating sFas levels in DCM were significantly higher than those in NC (2.42±1.02 vs 1.66±0.20 ng/ml, p=0.015). Patients with DCM were stratified into 2 groups [group I (n=15): sFas ≥2.06 ng/ml; group II (n=18): sFas <2.06 ng/ml] on the basis of the mean value plus 2SD of circulating sFas level in NC. The circulating sFas level was significantly increased in relation to the severity of heart failure and correlated positively to left ventricular end-diastolic pressure in DCM. However, there were no significant differences in left ventricular dimension between the 2 groups. There were 5 deaths from worsening heart failure in group II, but there were no deaths in group I during the follow-up period. In conclusion, circulating sFas levels were increased in patients with DCM. Circulating sFas levels are increased in proportion to the severity of heart failure and may provide prognostic information independent of left ventricular geometry. (Jpn Circ J 1998; 62: 873 - 876)

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The objective of this study was to investigate the effects of inhaled nitric oxide (NO) on chronic pulmonary hypertension (PH). Thirty patients with valvular heart diseases (n=8, group A), chronic lung diseases (n=16, group B), primary PH or PH due to collagen disease (n=6, group C) were studied. NO was delivered for 20 min at concentration of 5, 10, and 20 ppm in spontaneous respiration. After inhalation, percentages of systolic pulmonary artery pressure (%SPAP) levels in group A were significantly decreased compared with those for pre-inhalation by 12%, 14%, and 14% at 5, 10 and 20 ppm, respectively (p<0.05). In group B, %SPAP also significantly decreased by 7, 10, and 14% at 5, 10, and 20 ppm, respectively (p<0.05). However, inhaled NO did not significantly affect %SPAP in group C (p=0.4). There was no significant difference in gas exchange in any of the groups. However, 4 out of 8 patients in group A and 10 out of 16 patients in group B showed decreased partial pressure of arterial oxygen in response to inhaled NO. This study demonstrated that inhaled NO is a selective pulmonary vasodilator in decreasing pulmonary artery pressure (PAP); however, the reaction was different in line with the background disease cause of PH. NO inhalation was most effective on patients with moderate PAP. Furthermore, higher concentrations of NO would be risky in some patients with chronic PH. (Jpn Circ J 1998; 62: 877 - 882)

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Radiofrequency catheter ablation (RF-CA) has been widely used to cure paroxysmal supraventricular tachycardia (PSVT). However, its use has never been reported in familial PSVT caused by an accessory atrioventricular pathway (AP), which is known as one of the typical familial cardiovascular diseases. Two cases of using RF-CA for familial PSVT due to APs are presented, in a brother and sister, supporting a potential genetic role in the developmental failure to lose the atrioventricular connection during fetal life. The sister, a 24-year-old woman, had intermittent episodes of palpitation accompanied by chest pain for 2 years. An electrophysiologic study (EPS) confirmed her clinical tachycardia was atrioventricular reentrant tachycardia (AVRT) due to a left lateral concealed AP, which was subsequently successfully ablated with RF-CA. The brother, a 22-year-old man, had a 5-year history of paroxysmal palpitation. A resting electrocardiogram showed a right bundle branch block and left axis deviation with a delta wave. During his EPS, AVRT was reproducibly induced and a manifest AP was localized and then ablated at the left posteroseptal site, resulting in disappearance of the delta wave. PSVT, however, recurred 1 month later and during a repeat EPS the tachycardia was proved to be AVRT due to a right anterior concealed AP. The right anterior AP was successfully ablated with RF-CA. Both patients remained asymptomatic for more than 3 years following the successful ablation procedures. (Jpn Circ J 1998; 62: 883 - 886)

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The difference in sympathovagal activity preceding non-sustained ventricular tachycardia (NSVT) was examined between patients with and without a circadian rhythm. Thirty-three patients' Holter monitoring data (41 NSVT episodes) were analyzed regarding the frequency domain measures (low-frequency component [LF: 0.04-0.15 Hz], high-frequency component [HF: 0.15-0.4 Hz], and the ratio of LF to HF [LF/HF]) for each 15-min average from 120 min before each episode of NSVT. The presence of a circadian rhythm was accepted when the rhythm adaptation was significant by cosinor analysis and the acrophase was located at night (22.00-06.00 h) in HF (HF-positive group, n=17), and during the daytime (10.00-20.00 h) in LF/HF (LF/HF-positive group, n=12). The negative groups were identified by the absence of a circadian rhythm (HF-negative group, n=16; LF/HF-negative group, n=21). The serial changes in the HF power before NSVT were significantly different between the HF-positive and -negative groups (p<0.05). The HF increased from 75-60 min before NSVT in the HF-positive group, whereas the HF decreased from 60-45 min in the HF-negative group. The serial changes in the LF/HF ratio were not significantly different between the LF/HF-positive and -negative groups. Thus, the circadian rhythmicity of vagal activity seems to have an important role in the genesis of NSVT. (Jpn Circ J 1998; 62: 887 - 892)

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How the amplitude of the R wave in lead V₅ (RV ₅) of the ECG represents the left ventricular (LV) mass was investigated in 894 students aged 15 (boys: 545, girls: 349). The influence of body composition [ie, percentage of body fat (%fat)] was taken into consideration. A significant correlation was found between RV₅ amplitude and LV mass for both genders. However, the relationship was stronger for boys than for girls. The students were then divided into 3 groups; that is, those at either the top or bottom 10th percentile (low or high-fat range) and the rest of the students (middle-fat range), depending on the % fat calculated by the bioelectrical impedance method. The significant correlation between RV₅ and LV mass was found only for the 2 groups of boys whose percentage fat was in the low or middle-fat range. The correlation coefficients were 0.40 and 0.34, respectively. Moreover, in the boys' low-fat range, the RV₅ of students whose LV mass was large (≥90th percentile), was significantly higher (p<0.01) than in the other ranges. Setting a particular cutoff point of RV₅ in the low-fat range of boys improved sensitivity as well as specificity (20-30% better among all boys) for detecting large LV mass. These observations suggest that classification of subjects by body composition could be improve the reliability of ECG assessment for left ventricular hypertrophy, although the gender and number of subjects in whom improvement is expected are limited. (Jpn Circ J 1998; 62: 893 - 899)

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The long-term effect of delapril hydrochloride, a non-sulfhydryl angiotensin converting enzyme inhibitor, on serum concentrations of procollagen type III amino-terminal peptide (PIIIP) and left ventricular mass (LVM) and function were investigated in 15 hypertensive patients. Patients were treated with delapril hydrochloride 30 mg/day po for 12 months. Blood samples and an echocardiogram were obtained before treatment and after 6 and 12 months of treatment. Blood pressure, PIIIP, and LVM significantly decreased associated with an increase in left ventricular fractional shortening and mean systolic and diastolic posterior wall velocity at 6 and 12 months of treatment. Positive correlations between PIIIP and LVM (r=0.49, p<0.005) and negative correlations between PIIIP and left ventricular fractional shortening (r=-0.31, p<0.05) were found. Delapril hydrochloride reduced PIIIP and LVM and improved cardiac function in hypertensive patients. (Jpn Circ J 1998; 62: 900 - 902)

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Exercise hypotension has been documented in patients with hypertrophic cardiomyopathy (HCM). Some investigators reported that this is due to an inadequate increase of systemic vascular resistance during or after exercise. The aim of this study was to investigate the pathogenesis of limb vascular response abnormalities in patients with idiopathic HCM. Thirteen patients with HCM and 9 healthy controls were administered an endothelium-dependent dilator (acetylcholine), a direct smooth muscle dilator (nitroglycerin), an alpha-adrenergic stimulator (phenylephrine), and a beta-adrenergic stimulator (isoproterenol) by intra-arterial infusion. Peripheral vascular resistance was assessed by forearm plethysmography at rest and during each infusion to obtain the percentage change in vascular resistance. Isoproterenol, acetylcholine and nitroglycerin produced dose-related vasodilatation with no significant differences between HCM patients and healthy controls. The percentage increase in vascular resistance was significantly less in HCM patients than in healthy controls after phenylephrine infusions of 0.5μg/min (155±38% vs 195±47%, mean ± SD, p<0.05) and 1.0μg/min (174±49% vs 238 ± 65%, p<0.05). Vasoconstriction mediated by alpha-adrenergic receptors appeared to be impaired in the peripheral vasculature of patients with HCM. (Jpn Circ J 1998; 62: 903 - 908)

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A national survey of endomyocardial biopsy procedures was conducted in Japan. Questionnaires were mailed to 852 institutions and statistical analysis of the 213 completed questionnaires (25.0% of the total) was performed. Cardiac biopsies were being performed at 134 of these institutions (62.9%), representing a 5.5-fold increase over 1980. A total of 19,964 cardiac biopsies have been performed in Japan. Specimens were obtained from the right ventricle at 113 institutions, and from the left ventricle at 76 centers. The Konno-Sakakibara bioptome was used at 32 institutions, whereas the long sheath method was used at 98 institutions. Sixty of the institutions (44.8%) had encountered ventricular wall perforation. The perforation rate of the two ventricles combined was 0.7% (147 of 19,964 cases), with a mortality rate of 0.05% (10 of 19,964 cases). Endomyocardial biopsy has become widespread in Japan, and its safety was ascertained by this national survey. (Jpn Circ J 1998; 62: 909 -912)

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The aim of this study was to investigate whether distensibility of the persistent ductus arteriosus (PDA) might predict its potential for vasoconstriction. Epinephrine-induced constriction and stretching were investigated in 10 patients with PDA. Age, sex, ductus type, its minimal diameter, its stretched minimal diameter, and its stretch index were compared between epinephrine responders and non-responders. Age, sex, weight or the configuration or size of the PDA did not predict stretchability. The stretch index was significantly greater in responders (1.7-2.0, 1.8±0.1) than in non-responders (1.3-1.7, 1.4±0.2, p<0.01). Stretching of the PDA may depend on the elasticity of the vascular wall, which in turn is determined by preservation of vascular smooth muscle. (Jpn Circ J 1998; 62: 913 - 914)

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The aim of this study was to clarify the role of the adenosine triphosphate (ATP)-sensitive potassium channel on the mechanism of ischemic preconditioning (IP). Thirty-five anesthetized dogs were divided into 5 groups: (1) Control (C), (2) IP, (3) intravenous infusion of nicorandil (Ni) prior to IP, (4) glibenclamide (Gl) pretreated with IP (Gl+IP), and (5) Gl pretreated with Ni (Gl+Ni). All groups had 60 min ischemia followed by 60 min reperfusion, and were analyzed by biochemical and morphological procedures. At the end of the 60-min reperfusion, %segment shortening in C indicated paradoxical bulging. This value had significantly recovered in IP and Ni groups, but it was still negative in the Gl+IP and Gl+Ni groups. Ca⁺⁺-ATPase activity of the sarcoplasmic reticulum (SR) was significantly decreased in C. In the IP and Ni groups, this activity was significantly maintained; however, in the Gl+IP and Gl+Ni groups it was similar to that in C. State 3 respiration of mitochondria showed similar changes in the SR. In the ultrastructural observations, severely damaged cells were not observed in the IP and Ni groups. These results indicated that an ATP-sensitive potassium channel opener enhanced the effects of IP and its blockade abolished these phenomena. It was conclude that the ATP-sensitive potassium channel may play a key role in the mechanism of IP. (Jpn Circ J 1998; 62: 915 - 924)

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The effect of cardiac sympathetic stimulation on cardiac contractile efficiency was studied in dogs. In 19 anesthetized and open-chest dogs, left ventricular (LV) pressure, LV volume, coronary blood flow and coronary venous oxygen saturation were measured simultaneously. The LV end-systolic pressure volume relations (ESPVR) and the relation between myocardial oxygen consumption (VO₂)-pressure volume area (PVA) were obtained during a transient occlusion of the inferior vena cava before and after sympathetic stimulation (9 V, 6 Hz, 40 sec) both with and without 50 mg/kg of 2,3-butanedione monoxime (BDM). Without BDM, sympathetic stimulation increased the slope of ESPVR by 62% (p<0.05), the slope of the VO₂-PVA line by 19% (p<0.05) and the y-axis intercept of the VO₂-PVA by 65% (p<0.05). With BDM, the increase in the slope of the VO₂-PVA line became insignificant although other responses were similarly preserved. These data imply that cardiac sympathetic stimulation decreases cardiac contractile efficiency through mechanisms by which norepinephrine-induced β-adrenergic activation enhances myosin ATPase-operating ATP hydrolysis in crossbridge formation. (Jpn Circ J 1998; 62: 925 - 932)

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Basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) have shown strong angiogenetic effects in ischemic animals; however, whether such a beneficial effect could be achieved using low doses remains to be determined. The effects of identical low-level doses of these substances on the creation of collateral circulation in canine acute hind limb insufficiency were evaluated. Anesthetized dogs that had undergone left femoral artery occlusion received 20μg (2μg/kg) intravenous boluses of either bFGF or VEGF 3 times at 2-day intervals for the first week only, animals on vehicle saline injection served as controls. All groups, control (n=8), bFGF-treated (n=8), and VEGF-treated (n=6) underwent angiography, blood flow measurement (in ml/min) on the day of ligation (day 0), and at 7, 14 and 28 days, then underwent ischemic limb muscle biopsy at 28 days. Angiogenic-treated groups showed remarkable enhanced collateral circulation at 7 days, which was maintained up to 28 days, and the main collateral source artery of the angiogenic-treated groups dilated by 14 days. Many neovascularized arterioles in specimens of the angiogenic groups were recognized without any tissue edema or necrosis. Even low doses of bFGF or VEGF were enough to augment collateral circulation with no side-effects, and short treatment after acute ischemia was effective. Low-dose bFGF or VEGF may be therapeutical effective options in patients with acute lower limb vascular disease. (Jpn Circ J 1998; 62: 933 - 939)

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Primary pulmonary hypertension is a disease with a high mortality rate and for which there is no satisfactory medical treatment. The safety of long-term inhalation of nitric oxide (NO) as a treatment is described. A 9-year-old girl inhaled NO for 32 weeks, accompanied with oral administration of beraprost sodium. Although NO did not improve her long-term prognosis, it eased the patient's dyspnea and increased her blood oxygenation. At doses of 20 ppm or more, attempts to withdraw from inhaled NO seemed to lead to an immediate elevation of the pulmonary artery pressure. This rebound phenomenon did not happen at doses under 5 ppm. This case study suggests that long-term inhalation of NO is safe and effective, but that pulmonary hypertension may rebound following withdrawal at higher doses of NO. (Jpn Circ J 1998; 62: 940 - 942)

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Retrograde conduction of the concealed accessory pathway (AP) is a prerequisite for the induction of atrioventricular reentrant tachycardia (AVRT). In patients with AVRT due to a concealed AP, the absence of retrograde conduction of the AP in the baseline state has rarely been reported.We report a case of AVRT due to a concealed left lateral AP, in which the retrograde conduction was absent in the baseline state and manifested by isoproterenol infusion. A 61-year-old man had suffered from intermittent palpitation for 17 years. A narrow QRS complex tachycardia with a retrograde P wave in the ST segment was recorded in 24-h Holter monitoring. An electrophysiologic study was performed while he was in a nonsedated state. No ventriculoatrial conduction over either the normal atrioventricular conduction system or the AP was demonstrated in the baseline state. Isoproterenol was infused at a rate of 1.0 μg/min. Retrograde conduction over the AP became manifest and AVRT was induced. The AP was ablated with radiofrequency energy at the left free wall. After ablation of the AP, no tachycardia was induced. To the authors'best knowledge, only 1 other similar case has been reported in the literature. (Jpn Circ J 1998; 62: 943 - 946)

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A 31-year-old male with slow ventricular tachycardia (VT) developed a nonsustained VT with prolongation of the JT intervals after injection of contrast medium and saline into the marginal vein of the coronary sinus. The earliest activation site of the VT existed in the epicardium of the left ventricular base. Adenosine triphosphate prevented induction of VT and prolongation of JT intervals. Ventricular premature contractions showing the same morphology as the VT were also inhibited by nicorandil and verapamil. The mechanism of the VT was suggested to be abnormal automaticity due to an increase in the Ca⁺⁺ current into cells after prolongation of the action potential duration induced by hypothermia. (Jpn Circ J 1998; 62: 947 - 951)

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