The 5' promoter region of endothelial cell nitric oxide synthase (ecNOS) gene has several features which are compatible with a constitutively expressed, so called "housekeeping" gene. These include absence of a TATA box and the presence of Sp1 binding sites situated near the transcription start site. The promoter also contains sequences which suggest that it may be regulated by a variety of transcription factor-mediated signals. Studies of cultured endothelial cells show that ecNOS expression is modulated by shear stress, transforming growth factor beta, inhibition of protein kinase C, and the state of proliferation. These experiments indicate that although the ecNOS is a "constitutively expressed" gene, its content in the endothelium is subject to modest degrees of regulation which may have important physiological and pathophysiological implications. (Jpn Circ J 1996; 60: 815 - 821)

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Coronary angiographic and risk factor (RF) characteristics were analyzed in 133 Japanese patients with ischemic heart disease (IHD) who were less than 40 years old and who had undergone coronary angiography (CAG) during the past 10 years at six university hospitals in the Tokyo area. We compared the coronary angiographic characteristics of the subject group with those of 216 controls with coronary sclerosis detected by CAG who were more than 40 years old (older control group) and the RF characteristics with those of 133 sex- and age-matched volunteers (younger control group). Sixty seven percent of the subjects (89 cases) were diagnosed as having myocardial infarction (MI) and 33% (44 cases) had angina pectoris (AP). Coronary artery disorders in this group consisted of 103 (77%) cases of coronary sclerosis, 20 (15%) cases of coronary spasm and 10 (8%) cases of miscellaneous diseases, eg, possible vasculitis with connective tissue disease, congenital anomalies, etc. The incidences of significant (≥75%) sclerotic narrowing in 0 vessels (31%) and 1 vessel (49%) in the subject group were significantly (p<0.01) higher than those in the older control group, while the incidence of multivessel disease was significantly (p<0.05) less in the subject group than in the older control group. The incidences of the following coronary risk factors were significantly (p<0.05) higher in the subjects than in the younger controls: smoking (83% vs 35%), hypercholesteremia (44% vs 10%), obesity (31% vs 9%), hypertension (29% vs 3%), familial IHD (28% vs 7%) and diabetes mellitus (19% vs 2%). Thus, zero- or single-vessel disease predominated in the younger subject group and the prevalence of coronary risk factors was significantly higher in the subject group than in the sex- and age-matched control group. A relatively high incidence of non-sclerotic coronary disease was seen, and the results suggest that smoking, hypertension and familial IHD are important risk factors for coronary vasospasm in younger patients. (Jpn Circ J 1996; 60: 822 - 830)

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The present study was conducted to investigate the effects of cilazapril on exercise tolerance and the hormone kinetics of catecholamines, the renin-angiotensin-aldosterone system and alpha-atrial natriuretic peptide (ANP) in patients in the chronic phase of acute myocardial infarction (AMI). The subjects consisted of 19 cases of AMI. Cardiopulmonary exercise testing was performed 1 month after the onset of AMI, and patients were randomly assigned to either a group treated with 1 mg/day of cilazapril (9 cases) and or an untreated group (10 cases). After the completion of 2 months of exercise training at the anaerobic threshold (AT), blood samples were taken during a cardiopulmonary exercise test and various hormones were measured. In comparing the parameters of exercise tolerance before and after the completion of exercise training there were no significant differences between the 2 groups with respect to oxygen uptake, oxygen pulse, or exercise time at AT or at peak exercise. With regard to temporal changes in exercise tolerance, oxygen uptake, oxygen pulse and exercise time all tended to increase in both groups. With regard to hormone kinetics, the alpha-ANP concentration at peak exercise was significantly lower, and the noradrenaline secretions also tended to be lower, in the cilazapril-treated group, even though the peak exercise time was similar in both groups. These results may be support the hypothesis that cilazapril mitigates the left ventricular load during exercise therapy in patients in the chronic phase of AMI. (Jpn Circ J 1996; 60: 831 - 840)

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Indices of heart rate variability are non-invasive indicators of neural control of the heart. To investigate the significance of changes in heart rate variability in neurally mediated syncope, we performed head-up tilt testing in 45 patients with syncope of undetermined etiology. Seventeen patients showed a negative response and 28 showed a positive response; 18 had a vasodepressor response (systolic blood pressure dropped ≥50% without a decrease in heart rate) and 10 had a vasovagal response (systolic blood pressure dropped ≥50% with a decrease in heart rate of ≥30%). The mean RR-interval, the standard deviation of normal sinus RR-intervals (standard deviation of RR-interval) and power spectra were measured in consecutive 2 min periods throughout the study. Power spectra consisted of low frequency (0.04-0.15 Hz), high ,frequency (0.15-0.40 Hz) and total spectra (0.01-1.0 Hz). Both high frequency spectra and the low/high frequency spectra ratio significantly changed with head-up tilt testing regardless of the response. However, high frequency, low frequency and total spectra increased in relation to symptoms. These changes were most profound in the high frequency spectra of subjects with a vasovagal response. Since high frequency spectra reflect parasympathetic tone, a profound change in the high frequency spectra implies that parasympathetic activities play a significant role in patients with a vasovagal response. The assessment of heart rate variability during head-up tilt testing can provide new insight into the pathogenesis of syncope of undetermined etiology. (Jpn Circ J 1996; 60: 841 - 852)

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Radiofrequency catheter ablation of the slow pathway is commonly used to treat atrioventricular (AV) nodal reentrant tachycardia. However, there has been little study of the follow-up assessment of AV nodal physiology. We compared AV nodal electrophysiological characteristics before, immediately after, and again 3 months after successful catheter ablation in 17 patients (mean age 50±16 years). Sinus cycle length, Wenckebach cycle length, A-H interval at a paced cycle length of 600 ms, effective refractory period and functional refractory period of the fast pathway were significantly changed immediately after catheter ablation, but had recovered 3 months after the procedure. There were no significant differences between the electrophysiological parameters immediately after catheter ablation and those 3 months after the procedure under the intravenous injection of atropine sulfate. We conclude that, due to changes in autonomic nervous tone, AV nodal electrophysiological characteristics are influenced immediately after catheter ablation of the slow pathway in AV nodal reentrant tachycardia. (Jpn Circ J 1996; 60: 853 - 860)

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The optimum potential of the slow pathway (SP) was investigated by determining the effectiveness and safety of high-radiofrequency catheter ablation to treat atrioventricular nodal reentrant tachycardia (AVNRT). The subjects consisted of 29 patients with AVNRT (11 men, with a mean age of 54±15 years). Three ablation methods were used: a) Method A used the earliest atrial activation site, which is retrograde to the slow pathway, b) Method SP used the SP potential, and c) Method SW, in which ablation was performed stepwise starting from the coronary sinus and moving toward the recording site of the His bundle potential. Five, 20, and 4 patients underwent Methods A, SP, and SW, respectively. The fewest number of applications was needed with Method SP (11±9, 6±4, and 13±9), and the delivered energy was also lowest with Method SP (9151±6119, 3712±2168, and 12183±4090 J, with Methods A, SP, and SW, respectively). In Method SP, the interval between the atrium and SP was significantly longer at sites which cured tachycardia, than at sites at which ablation was ineffective (88±26 vs 66±22 msec, p<0.05). The SP potential showed a humped shape in 18 of 20 patients. Method SP was the most efficient ablation method for treating AVNRT. (Jpn Circ J 1996; 60: 861 - 870)

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Magnesium affects cardiac function, although until the recent development of a new ion-selective electrode no method existed for measuring the physiologically active form of magnesium, free ions (iMg²⁺), in the blood. We investigated the antiarrhythmic effect of magnesium sulfate administered to critically ill patients with cardiac arrhythmias and reduced iMg²⁺ as determined using the ion-selective electrode. Eight patients with a low iMg²⁺ Ievel (less than 0.40 mmol/L) were given intravenous magnesium sulfate (group L). Magnesium sulfate was also administered to patients with a normal iMg²⁺ level (more than 0.40 mmol/L) but who did not respond to conventional antiarrhythmic drugs (group N). Intravenous magnesium sulfate significantly increased the iMg²⁺ level in patients in group L from 0.35±0.06 mmol/L (mean±SD) to 0.54±0.09 mmol/L (p<0.01), and had an antiarrhythmic effect in 7 of the 8 patients (88%). However, in group N patients, intravenous magnesium sulfate had an antiarrhythmic effect in only 1 of the 6 patients (17%) (p<0.05 vs group L). These results suggest that intravenous magnesium sulfate may be effective in the acute management of cardiac arrhythmias in patients with a low serum iMg²⁺ level. (Jpn Circ J 1996; 60: 871 - 875)

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Changes in myocardial lactate metabolism during ramp exercise were investigated through great cardiac vein catheterization in 15 patients with effort angina (EA) and 7 patients with microvascular angina (MVA). The exercise test was performed using a supine bicycle ergometer. Blood samples were obtained from the great cardiac vein (GCV) and the radial artery each minute during exercise. Patients in the EA group showed a point at which the lactate extraction ratio (LER) and the ST Ievel decreased rapidly during exercise. This point was clearly recognized in 12 of 13 patients, and may represent the ischemic threshold. Both the LER and ST Ievel showed similar changes during exercise, and these values were significantly different between the ischemic threshold and peak exercise (p<0.01). Both the LER and ST Ievel were strongly correlated with the duration of exercise until the threshold (r=0.703). In the MVA group, both the LER and ST Ievel during exercise continuously decreased throughout exercise without an ischemic threshold in all of the subjects. Endomyocardial biopsy revealed sclerosis of small arteries in the myocardium in all of the patients. In both effort angina and microvascular angina, a close correlation was noted between the change in ST and that in the myocardial lactate extraction ratio. (Jpn Circ J 1996; 60: 876 - 888)

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The purpose of this study was to clarify whether continuous infusion of recombinant tissue plasminogen activator (rtPA) prevents intimal hyperplasia at the site of arterial injury. Forty-three Kurosawa and Kusanagi hypercholesterolemic (KHC) rabbits which underwent balloon angioplasty of the right common iliac artery were randomly divided into 2 groups; rtPA for 7 days (n=29) and untreated (n=14). The former group was subdivided into a high-dose group (n=15) (2 mg/kg per day continuously for 7 days after 3 mg/kg for 4 h) and a low-dose group (n=14) (0.6 mg/kg per day for 7 days after 0.6 mg/kg for 4 h). Balloon angioplasty was performed with a 2.5-mm balloon (3×60-sec, 6-atm inflations at 60-sec intervals) 1 h after the initiation of rtPA infusion via an ear vein. The iliac arteries of the rabbits were histologically studied at 28 days. The cross-sectional areas of the intima, media, and adventitia were calculated at the site of intimal hyperplasia. The intimal cross-sectional area was 0.07±0.11 (mean±SD) mm² for the high-dose rtPA group and 0.11±0.07 mm² for the low-dose rtPA group, and both of these values were significantly less than that for the control group (0.57±0.21 mm² p<0.01). The ratio of the intimal to medial cross-sectional area was significantly (p<0.01) Iower for the rtPA groups than for the control group (high-dose rtPA; 0.10±0.13, Iow-dose rtPA; 0.21±0.19, control; 1.25±0.55). In conclusion, continuous infusion of rtPA for 7 days prevented intimal hyperplasia after balloon injury. (Jpn Circ J 1996; 60: 889 - 894)

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Congenital heart disease in adults has become a special area of cardiovascular interest, but remains a relatively unfamiliar discipline. Advances in diagnostic and surgical techniques have had a striking impact on longevity in infants and children with congenital heart disease. Nevertheless, since true cures are rare, long-term care is obligatory for most if not all patients. In parallel with diagnostic and surgical developments, advances in medical management have had a major impact on life span in both postoperative and unoperated patients. Who will assume responsibility for the long-term care of these adult patients? Relatively few medical cardiologists are equipped to do so and relatively few pediatric cardiologists are sufficiently well versed with the accrued problems of aging. Accordingly, the current approach involves collaboration between pediatric and medical cardiologists. The purpose of this report is to underscore the importance of this collaboration, and to focus on 2 particular issues - the management of cyanotic congenital heart disease and the management of congenital heart disease and pregnancy. (Jpn Circ J 1996; 60: 895 - 897)

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A 24-year-old man was hospitalized for an investigation of cardiac enlargement. Serum hyaluronic acid was increased to 238 ng/ml. Echocardiogram showed pericardial effusion with an area of increased density adjacent to the anterolateral wall of the left ventricle. A soft-tissue mass within the pericardial space was enhanced with gadolinium DTPA on magnetic resonance imaging. Open biopsy confirmed the presence of a malignant mesothelioma. Magnetic resonance imaging provided useful information regarding the tumor. (Jpn Circ J 1996; 60: 898 - 900)

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The best-known type of adenosine-sensitive ventricular tachycardia is idiopathic and of right ventricular outflow origin; however, there is little information about other types of adenosine-sensitive ventricular tachycardia. Idiopathic adenosine-sensitive ventricular tachycardia is common in the young. An 87-year-old man with ventricular tachycardia was admitted to our hospital. His ventricular tachycardia was sensitive to adenosine triphosphate, edrophonium, verapamil, and Valsalva's maneuver. He had experienced no anginal episodes. His ventricular tachycardia was thought to be idiopathic. We report this very rare case of adenosine-sensitive ventricular tachycardia, which was not derived from the right ventricular outflow tract, in a very elderly male. (Jpn Circ J 1996; 60: 901 - 907)

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