Humankind is on a similar evolutionary process to animals. Biological reactions in the human heart will be reviewed, and consideration will be made about what can be done in cardiology, from the viewpoints of basic, clinical and community medicine. Functional reactions of the heart to acute loading (exercise, etc) comprise myocardial contractility, preload, pump function and peripheral factors, and are mobilized step by step in that order, to maintain normal functioning. Morphological reactions to chronic loading (hypertension etc) comprise hypertrophy and dilatation, which are caused by mechanical and nonmechanical factors, but may not always be mobilized to maintain normal functioning. Various neurohumoral factors take part in the mechanisms, and modifications, of these reactions. They act in a complex manner according to the biological conditions, and may not always act to maintain normal functioning. The biological reactions in the heart (ie, Basic Cardiology) should not be interpreted as having purpose; that is, putting a value on humankind, although medical treatment (Clinical Cardiology) and the solution of health problems in the community (Community Cardiology) should be done from this viewpoint. (Jpn Circ J 1999; 63: 737 - 743)

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The aim of this study was to demonstrate that blood pressure (BP) has to be standardized according to its circadian variability, including the properties shown in its circadian rhythm. The BP time-qualified standards were derived from a sample of 644 clinically healthy normotensive Japanese subjects (320 males, 324 females; age range, 18-93 years), stratified by age-group and gender, who underwent noninvasive ambulatory monitoring according to a fixed protocol. The monitored data series shows that BP exhibits a within-day variability at any age of life in both males and females. Additionally, the monitored data series shows that BP exhibits a significant circadian rhythm at any age of life in both males and females. The age- and sex-related reference limits for the BP within-day variability constitute the time-qualified standards against which both the casual and monitored BP measurements can be compared in order to detect whether or not they are compatible with normotension. The reference limits for the BP circadian rhythm represent the rhythmometric standards against which the BP oscillatory curve can be compared in order to detect whether or not they are compatible with a physiological circadian rhythm. (Jpn Circ J 1999; 63: 744 - 751)

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To evaluate the functional recovery after coronary bypass surgery in patients with severe left ventricular (LV) dysfunction (ejection fraction (EF) ≤35%), 100 consecutive patients with viable myocardium in the territory supplied by the left anterior descending artery (LAD) underwent coronary bypass grafting. In addition, cardiac catheterization and single-photon emission computed tomography (SPECT) perfusion imaging with thallium-201 were repeated 1-year postoperatively. Although 12 patients with severe LV dysfunction were preoperatively in a worse New York Heart Association functional class (3.1±0.7 vs 2.4±0.8; p<0.01), had a higher incidence of heart failure (10/12 vs 14/88; p<0.001) and had a worse LVEF (29±5 vs 61±14%; p<0.001) compared with 88 patients without severe LV dysfunction, the operative mortality was similar in the 2 groups (1/12 vs 2/88; p=NS). The postoperative NYHA functional class in the patients with severe LV dysfunction was similar to that in the patients without such dysfunction (1.6±0.7 vs 1.3±0.6; p=NS). In addition, the 1-year postoperative study revealed a significant improvement in the thallium defect score in both the LAD territory (1.7±1.2 to 0.7±1.0, p=0.01) and all the territories (5.2±2.2 to 3.2±1.9, p=0.002) in patients with severe LV dysfunction, whereas no improvement in defect score was found in either of these territories in those without severe LV dysfunction (LAD: 0.6±1.4 to 0.4±1.2, p=NS; All: 1.9±2.2 to 1.8±2.0, p=NS). Furthermore, a marked 1-year postoperative improvement (15-24%; 95% confidence interval) in LVEF (29±5 to 48±10%, p<0.001) was demonstrated in patients with severe LV dysfunction, but not in those without such dysfunction (60±13 to 61±11%, p=NS). These results indicate that myocardial viability in the LAD territory, as demonstrated by thallium-201 SPECT perfusion imaging, predicts a significant improvement in functional class and LVEF of at least 10% or more after coronary artery bypass grafting in patients with severe LV dysfunction. (Jpn Circ J 1999; 63: 752 -758)

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The present study examined the genetic contribution of the human β₂ bradykinin receptor gene in Japanese subjects with essential hypertension, and identified a -58T/C polymorphism of the core promoter that might be responsible for essential hypertension in Japanese. The study consisted of 100 hypertensive subjects and 100 age- and sex-matched controls. The allelic frequencies were 0.575 for the C allele and 0.425 for the T allele in hypertensive subjects, and 0.465 for the C allele and 0.535 for the T allele in normotensive subjects. The allelic frequencies were in Hardy-Weinberg equilibrium. Significant differences between hypertensive and normotensive subjects were seen in the genotypes distribution (p=0.049) and allelic frequencies (p=0.028), and the β₂ bradykinin receptor gene variant was associated with human essential hypertension in this Japanense population. This new marker may provide a valuable tool for assessing the risk for putative bradykinin-associated common diseases, such as hypertension, and cardiovascular diseases with genetic determinism. These results suggest that the -58 polymorphism of the human β₂ bradykinin receptor gene is an independent risk factor for essential hypertension in the Japanese population. (Jpn Circ J 1999; 63: 759 - 762)

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The objective of the present study was to evaluate the hemodynamic relationship between the left atrium (LA) and left ventricle (LV) during atrial systole in the presence of an elevated left ventricular end-diastolic pressure (LVEDP) and LV failure using pulsed tissue Doppler imaging (TDI). Fifty-three patients with LV systolic dysfunction and no regional LV asynergy were divided into 3 groups: relaxation failure group (RF, n=20) with a ratio of peak early diastolic to atrial systolic velocity of the transmitral flow (E/A) ≤ 1; pseudonormalization group (PN, n=19) with 1 < E/A < 2; and restrictive group (RS, n=14) with E/A ≥ 2. In addition, 20 normal patients (E/A ≥ 1) were studied as a control group. The transmitral and pulmonary venous flow velocities were recorded by transesophageal pulsed Doppler echocardiography. The wall motion velocity patterns were recorded at the middle portion of the LV posterior wall (LVPW) and at the mitral annulus (MA) of the LVPW site in the apical LV long-axis view by transthoracic pulsed TDI. The LVEDP was significantly greater in the PN and RS groups than in the RF and control groups. The mean pulmonary capillary wedge pressure was greatest in the RS group. The percent fractional change of the LA area during atrial systole determined by 2-dimensional echocardiography was significantly lower in the RS group than in the PN group. The peak atrial systolic pulmonary venous flow velocity was significantly greater in the PN group than in the RS group. The peak atrial systolic motion velocity (Aw) at the LVPW was significantly lower in the PN and RS groups than in the RF and control groups. The Aw at the MA was significantly lower in the RS group than in the other groups. There was no significant difference in Aw between the LVPW and MA in the RS group, whereas Aw at the MA was significantly greater than that at the LVPW in the PN group. In conclusion, the measurements of Aw at the LVPW and MA can be used to noninvasively evaluate the hemodynamic relationship between the LA and LV during atrial systole in patients with LV failure. (Jpn Circ J 1999; 63: 763 - 769)

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The effect of an endothelin (ET) A/ETB receptor antagonist, TAK-044, and/or an angiotensin converting enzyme (ACE) inhibitor, temocaprilat, on myocardial metabolism and contraction during ischemia and reperfusion was examined by phosphorus 31-nuclear magnetic resonance (³¹P-NMR) in Langendorff rabbit hearts. After normothermic 15 min global ischemia, 60 min of postischemic reperfusion was carried out. TAK-044 and/or temocaprilat was administered from 40 min prior to the global ischemia. Adenosine triphosphate (ATP), creatine phosphate, inorganic phosphate, pH, left ventricular systolic developed pressure (LVDev.P), left ventricular end-diastolic pressure (LVEDP) and coronary flow were measured. Twenty-eight hearts were divided into 4 experimental groups consisted of seven hearts each: Group I consisted of controls, Group II was perfused with TAK-044 (10 ^-6 mol/L), Group III was perfused with temocaprilat (10^-6 mol/L), and Group IV was perfused with TAK-044 (10^-6 mol/L) in combination with temocaprilat (10^-6 mol/L). Group II showed a more early recovery of ATP during postischemic reperfusion (82±3%) compared with Group I (71±3%). Group III showed a significant inhibition of the decrease in ATP during global ischemia (54±3%) compared with Group I (45 ±3%). Group IV also showed a significant marked inhibition of the decrease in ATP during global ischemia (59±5%) and a more significant improvement on recovery of ATP during postischemic reperfusion (86±3%) compared with the other 3 groups. There were no differences in LVDev.P, LVEDP and coronary flow among these groups. In conclusion, TAK-044 in combination with temocaprilat had a significant potentiation on myocardial metabolism during both ischemia and reperfusion. (Jpn Circ J 1999; 63: 770 - 774)

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Immunologic injury to heart allografts is an initial and essential event in the pathogenesis of graft coronary artery disease (GAD). A variety of cytokines expressed in heart allografts modify both acute rejection and chronic inflammation, and could contribute to the development of GAD. The present study investigated the gene expression of interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and Fas ligand in chronically rejecting DBA/2-to-B10.D2 mouse heart allografts at defined intervals of 7, 14, 28, or 70 days after transplantation by semiquantitative reverse transcriptase-polymerase chain reaction. GAD developed gradually, showing the highest value for mean intima/media ratio at day 70. Fas ligand, and the Th1 cytokines IL-2 and IFN-γ, were vigorously induced in allografts at day 7, when histology showed pronounced parenchymal rejection, and rapidly decreased by day 28. However, the level of mRNA expression of Th2 cytokines, IL-6 and IL-10, and other inflammatory cytokines, TNF-α and IL-1β, were still elevated on day 28. The persistent expression of specific cytokines suggests an important role in chronic inflammation. Thus, a persistently high level expression of inflammatory cytokines could be associated with chronic inflammation in the allografts, which promotes the development of GAD. (Jpn Circ J 1999; 63: 775 - 782)

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Previous studies have shown that the autonomic nervous system plays an important role in the genesis of ventricular tachycardia (VT) in patients with long QT syndrome, and in cesium chloride (Cs)-induced VT in animals. The present study investigated whether baroreflex sensitivity predicts the induction of VT by Cs in the rabbit in vivo. Monophasic action potentials (MAPs) of the left ventricular endocardium were recorded simultaneously with the surface ECG in 27 rabbits. Rabbits were divided into 4 groups based on the Cs-induced ventricular arrhythmias: (1) no ventricular premature contractions (No-VPC group), (2) single or paired VPC (VPC group), (3) monomorphic VT (MVT group), and (4) polymorphic VT (PVT group). Baroreflex sensitivity was significantly lower in the MVT and PVT groups than in the No-VPC and VPC groups. The plasma norepinephrine concentration before Cs injection was significantly higher in the MVT group than in the other 3 groups, and the norepinephrine concentration after Cs injection was significantly higher in the MVT and PVT groups than in the No-VPC and VPC groups. Baroreflex sensitivity was negatively correlated with the norepinephrine concentration before Cs injection. These results suggest that autonomic nervous system dysfunction, as defined by reduced baroreflex sensitivity, and elevated plasma norepinephrine concentrations predict increased susceptibility to Cs-induced VT. (Jpn Circ J 1999; 63: 783 - 788)

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The authors recently developed a cone-beam computed tomography (CT) scanner and this report presents their evaluation of its potential for thoracic vascular imaging. An X-ray tube and a video-fluoroscopic system were rotated around the objects and 360 projected images were collected in a 12-s scan. Each image was digitized and a 3 dimensional (D) image (256×256 ×256 voxel volume with a voxel dimension of 0.9 ×0.9×0.9 mm) was reconstructed. Two different 3D-CT angiographies were investigated in 2 pigs: right atriography and thoracic aortography. Each pig was anesthetized, mechanically ventilated and positioned within the scanner. Contrast agent was infused through the right atrium or the aortic root at a rate of 3 ml/s during the scan. The right atriography scan clearly delineated the anatomy of the pulmonary artery, heart chambers and thoracic aorta. The thoracic aortography scan also clearly delineated the aortic anatomy including the internal thoracic and intercostal arteries. In conclusion, cone-beam CT angiography is potentially useful for thoracic vascular imaging. (Jpn Circ J 1999; 63: 789 - 793)

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The relation between mycarditis and dilated cardiomyopathy (DCM) is controversial. To clarify the pathogenic mechanism of these diseases, the present study examined the effect of repetitive inoculation with coxsackievirus B3 (CVB3) in post-myocarditic mice. Inbred 3-week-old A/J mice were inoculated intraperitoneally with CVB3 (Nancy strain; 2×10⁴ plaque-forming units) and reinfected in the same manner with CVB3 at 40 weeks (3W+/40W+). All mice were killed at 42 weeks old. The weight of the hearts of the 3W+/40W+ group were significantly increased compared with those of the 3W-/40W+ group, and both the heart weight/body weight and lung weight/body weight ratios of the 3W+/40W+ group were also significantly increased over those of the 3W-/40W- group, although the levels of serum neutralizing antibody titers were significantly increased in the 3W+/40W+ group over the level of the other groups. No increase in inflammatory cell infiltration or fibrosis progression was observed in the 3W+/40W+ group relative to the 3W+/40W- group, but the second inoculation resulted in a significant left ventricular dilatation and in left and right ventricular free wall thinning (3.31±0.20 mm vs 2.61±0.19 mm, p<0.05; 0.54±0.09 mm vs 0.72±0.16 mm, p<0.05, respectively). The sarcomere length was also significantly increased in the 3W+/40W+ group compared with that of the other groups, as determined by electron microscopy. Degenerative or necrotic areas in the infected hearts were not stained with anti-mouse IgG antibody, but were stained, only in 3W+/40W+ mice, with anti-mouse IgM antibody. The concentrations of TNF-α in the hearts of the 3W+/40W+ group were increased significantly over those of the 3W+/40W- group. Repetitive CVB3 infection produced cardiac dilatation without inflammatory cell infiltration in post- myocarditic mice. Autoimmunity mediated by the circulation of certain antibodies (eg, antibodies against the CVB3 genome or a CVB3-related protein) may be part of the pathogenic mechanism for this phenomenon. Thus, repetitive virus infection might contribute to the pathogenesis of cardiac dilatation. (Jpn Circ J 1999; 63: 794 - 802)

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This report presents a case of occult constrictive pericarditis and mitral valve insufficiency following chest radiotherapy. A 44-year-old man had received radiotherapy for the treatment of Hodgkin's disease 8 years ago. At age 40 years, effusive pericarditis occurred and he was treated with intrapericardial drainage. Biopsy revealed a fibrotic and thickened pericardium. He developed congestive heart failure 3 years later. The patient was found to have occult constrictive pericarditis and mitral valve insufficiency. He underwent mitral valve replacement, tricuspid annul plasty, and pericardiectomy. Although there is the benefit of cure for the Hodgkin's disease, the prognosis after treatment is affected by radiotherapy-induced heart disease. After radiotherapy of the chest and mediastinum, long-term cardiological follow-up is recommended in order to detecting patients with radiation-induced heart disease, such as the present case. (Jpn Circ J 1999; 63: 803 - 805)

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In patients with pseudoxanthoma elasticum, severe organic coronary artery stenosis often occurs without coronary risk factors. However, this report presents the case of a 49-year-old woman with pseudoxanthoma elasticum who had coronary artery spasm with an angiographically normal coronary artery. In addition, coronary artery spasm was provoked with dipyridamole thallium-201 cardiac imaging. (Jpn Circ J 1999; 63: 806 - 808)

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An extremely rare case of a coronary artery fistula with a concomitant saccular aneurysm is presented. A 65-year-old woman, who had a history of chest bruising 5 years earlier, suffered from chest pain, which was diagnosed as being due to left coronary artery-pulmonary artery fistulae concomitant with a giant saccular coronary artery aneurysm. Suture closure of the afferent coronary artery to the aneurysm, aneurysmorrhaphy, and transpulmonary closure of coronary artery-pulmonary artery fistulae were performed. The postoperative course was uneventful and the patient was well at 3 months after the operation. Because the risk of surgery appears to be less than the potential development of fatal complications, it is recommended for the treatment of coronary artery fistula with a concomitant saccular aneurysm. (Jpn Circ J 1999; 63: 809 - 812)

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A patient with a right ventricular infarction was resuscitated with percutaneous cardiopulmonary support (PCPS), after attempts at reperfusion, high-dose inotropic support and intra-aortic balloon counterpulsation failed to improve the hemodynamic compromise. Emergency PCPS improved the cardiogenic shock and the reduced right ventricular load, allowing the ischemic right ventricle to recover in the setting of unsuccessful reperfusion. This case demonstrates the use of PCPS as a hemodynamic support device for spontaneous recovery of the ischemic right ventricle. PCPS may be a potential therapy for patients with right ventricular infarction. (Jpn Circ J 1999; 63: 813 - 815)

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The present report concerns a case of very low plasma levels of atrial natriuretic peptide (ANP) accompanying severe pulmonary hypertension due to mitral stenosis. There was remarkable fibrosis in the atrium and ANP secretion may have been insufficient. Low-dose infusion (0.025μg kg^-1 min ^-1) of synthetic human α-ANP infusion was very effective in improving the pulmonary hypertension. (Jpn Circ J 1999; 63: 816 - 818)

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A 61-year-old male was referred to the surgical ward by cardiologists because of a diagnosis of unstable angina with 3-vessel disease. On preoperative left internal thoracic arteriography, a large first intercostal branch was found at the proximal portion. Selective arterial embolization of the branch of the left internal thoracic artery (LITA) was carried out preoperatively. At 2 days after embolization, the Doppler peak flow velocity and diameter of the LITA were increased and enlarged compared with before the procedure. However, a large reverse wave following after the first systolic peak flow of the LITA was newly detected after embolization. Upon operation, the LITA was found to be occluded at the 2nd intercostal space due to thrombus formation. Therefore, the right internal thoracic artery was anastomosed to the left anterior descending artery and coronary reversed saphenous vein grafts were joined to segment 4PD of the right coronary artery. The postoperative course was uneventful. There has been no previous report of an LITA branch being embolized preoperatively. It was possible to diagnose the graft problem by detecting the altered Doppler wave form of the LITA. (Jpn Circ J 1999; 63: 819 - 821)

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A 57-year-old male with primary cardiac angiosarcoma was initially admitted for cardiac tamponade. Pericardiocentesis was performed twice preoperatively, but the bloody pericardial fluid was cytologically negative for malignant cells. The tumor in the right atrium was resected during cardiopulmonary bypass. The resected tumor was 5.5×4.5×3.0 cm in size and the diagnosis of cardiac angiosarcoma was made histologically. There were no tumor cells in the surgical margin. Unfortunately the patient died 3.5 months after surgery due to multiple recurrence in the pericardium. A suitable therapy for cardiac angiosarcoma is still controversial, but early antemortem diagnosis and more aggressive combined treatment should be considered. (Jpn Circ J 1999; 63: 822 - 824)

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