We made a clinical and statistical evaluation of the occurrence of acute myocardial infarction with respect to the relation between its occurrence and the meteorology of the cold inland area of Hokkaido (the Kamikawa Basin) over a period of 10 years (1976-1985). A total of 581 cases were studied. Monthly fluctuation of incidence was not found to be statistically significant. A cold period in the Kamikawa Basin was defined in this study as the period when ordinary mean atmospheric temperatures were below 0°C (from 7 Nov. to 16 Apr.). Canonical discriminant analysis was applied to 10 meteorological factors between the days with occurrences and those without occurrences (245 days vs 245 days) in the cold periods of the investigated 10 years, and between the days with outdoor occurrences and those without occurrences (37 days vs 37 days). In order to compare the regional difference, this analysis was done o the same 10 factors for the cold periods over 3 years in Yamagata (46 days vs 46 days). The F values of 0.0003, 0.0155 and 0.0098 respectively in the above 3 analyses were small (&Li;F¹₉(0.25)=1.51). A circadian rhythm of 2 cycles/day was recognized concerning the time of occurrence by power spectral analysis of the data of 562 patients for whom the time of the onset of myocardial infarction was known. Subdividing the patients into 2 groups according to physical activity just before the occurrence, the group who experienced an occurrence at rest showed a rhythm of 1 cycle/day, and the group who experienced an occurrence on effort showed a rhythm of 2 cycles/day. Therefore, the 10 meteorological factors could not discriminate the probabilities between the days with occurrences and the days without occurrences of myocardial infarction in the cold periods. On the other hand, it was suggested that biological intrinsic rhythm participates in triggering the occurrence of myocardial infarction.

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The presence of atrial natriuretic polypeptide (ANP) was immunohistochemically demonstrated in the formalin-fixed and paraffin-embedded tissues of 25 autopsied normal human hearts using monoclonial antibody. The ANP amounts were immunohistochemically semiquantified and compared with were divided into 5 groups according to the interval of formalin fixation or the length of time between death and fixation. Formalin-fixation intervals were one week in group 1A and 1B; 1 year in group 2; 4 to 5 years in group 3 and 10 to 12 years in group 4. The hearts of group 1A, 2, 3 and 4 were fixed within 5 hours after death. Those of group 1B were fixed 14 to 18 hours at 4°C. After fixation, the left and right atrial appendages (LAA and RAA), the left and right atrial free walls (LA and RA), the left and right ventricular free walls (LV and RV) and the ventricular septum (VS) were transmurally dissected from each heart. They were embedded in paraffin, cut into 4μm sections and immunohistochemically stained by the avidin-biotin-peroxidase complex (ABC) method using monoclonal antibody against α-human ANP. Under a light microscope, they were evaluated semiquantitatively according to the incidence of ANP-positive cells and the intensity of immunostaining. For every heart i group 1A, the tissue concentrations of ANP in the different parts were also measured separately by RIA before fixation. ANP-positive myocytes were noted in the atria of all hearts of all groups, but no in any ventricular myocytes. Both their incidence and grade in the atria were similar among groups 1A, 1B and 2. However, they were less in group 3, and least in group 4 among all groups. For all groups, they decreased in following order: LAA>RAA≒LA>RA; the inner 1/3>the middle 1/3>the outer 1/3 of the atrial walls. The order in LAA, RAA, LA and RA was consistent with the results of RIA measurements on group 1A. In conclusion, the immunoreactivity of ANP in paraffin-embedded sections is well preserved for one year formalin-fixation interval. However, the same difference of tissue distribution in ANP is seen even in more long-term formalin-fixed hearts. Thus, the immunohistochemical method is useful for retrospective studies of ANP, if the formalin-fixation interval is considered.

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Eighty-seven unipolar electrocardiograms were simultaneously recorded before and after symptom-limited treadmill exercise in 75 patients with coronary artery narrowing (⩾70%) and without previous myocardial infarction. body surface distributions of ST segment depression were divided into 3 types; upper, lower, and diffuse types. Body surface distributions of U-wave inversion were divided into 2 types; upper, and lower types. These distribution patterns were compared with the location of ischemia determined by T1-201 exercise myocardial perfusion imaging. For ST-segment depression, a considerable number of patients had diffuse-type ST depression, whether the site of ischemia was anterior (22/32, 69%), inferior (18/27, 67%) or both (5/5, 100%). However, upper-type ST depression was associated with anterior ischemia, and lower-type ST depression, with inferior ischemia. The sensitivity and specificity of the spatial distribution of ST depression in identifying the myocardial ischemic site were 27% and 95% for anterior ischemia respectively, and 28% and 88% for inferior ischemia, respectively. The incidence of U-wave inversion was moderate (29/75, 39%), but the distribution pattern was specific for the site of ischemia; upper-type U inversion associated with anterior ischemia, and lower type with inferior ischemia. The sensitivity and specificity were 59% and 100% for anterior ischemia respectively, and 22% and 100% for inferior ischemia respectively. By a combination of ST-depression and U-inversion, the sensitivity and specificity were 78% and 95% for anterior ischemia, and 44% and 88% for inferior ischemia. Body surface electrocardiographic mapping provided important information in the non-invasive diagnosis of the site of myocardial ischemia.

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T1-201 imaging and first-pass radionuclide ventriculography (RNV) by 4 min infusion of 0.56 mg/kg dipyridamole were performed on 22 patients with coronary artery disease in order to know the relationship of myocardial perfusion and left ventricular function after dipyridamole-infusion, and thereby to define whether T1-201 images were divided into anterior, apical, and infero-posterior segments, and segmental perfusion defects were categorized as reversible, fixed and no defect. RNV on the 30-degree right anterior oblique view was also divided into anterior, apical, and infero-posterior wall to be evaluated for regional wall motion by a 5 point score before and after dipyridamole. Changes in left ventricular ejection fraction (LVEF) with dipyridamole were also calculated. Normal responses of regional wall motion and LVEF to dipyridamole were established from the data of 14 normal subjects. Reversible defects were closely associated (69%) with an abnormal response of regional wall motion (score decrease of 1 or more after dipyridamole). Both fixed defects and no defects showed little association with abnormal response of regional wall motion. Moreover, 77% of the patients having reversible-defect segment showed an abnormal response of LVEF (reduction of 3% or more following dipyridamole). However, patients without reversible defect did not show and abnormal response to dipyridamole. These results suggest that dipyridamole-induced T1-201 defects represent a myocardial ischemia which causes a reduction of ventricular function.

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Multiple coronary artery bypass grafting with more than 4 grafts has been carried out in 64 Japanese patients during a 3.5 year period. There were 55 males and 9 females; ages range from 34 to 75 with a mean of 58.9 year old. Double, triple and left main disease were noted in one (2%), 54 (84%) and 9 (14%) patients, respectively. There was 54 (84%) stable and 10(16%) unstable angina pectoris, and 28 (44%) patients had previous myocardial infarction. The saphenous vein graft was used for all patients with a preferential use of sequential graft (84%). The internal mammary artery graft was used in 55 (86%) patients and the right gastroepiploic artery graft was used in 6 (9%) patients. There were 2 (3.1%) early and 2 (3.1%) late deaths. New Q wave was noted in 2 (3.1%) patients and intraaortic balloon pumping was required in 3 (4.7%) patients. The mean number of grafts was 4.4 ranged from 4 to 7, and the mean aortic cross clamp time and cardiopulmonary bypass time was 74.5 min and 134.3 min, respectively. Graft patency within 6 postoperative months was 86% (120/140) in saphenous veins, 96% (52/54) in internal mammary arteries and 100% (5/5) in gastroepiploic arteries. Relief of angina was noted in 58 (96.7%) of 60 survivors. It was concluded that the increase in the number of coronary artery anastomoses does not increase surgical risk and favorable outcome and acceptable graft patency can be obtained by multiple grafting for patients with severe multivessel coronary artery disease.

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Real-time flow imaging of pulmonary regurgitation (PR) by two-dimensional pulsed Doppler echocardiography was performed in 34 patients after repair of tetralogy of Fallot. The right ventricle and pulmonary artery were demonstrated in the parasternal short axis view and PR flow was visualized. The image was frozen when the velocity of regurgitant flow was maximum at the level of the pulmonary valve. Pulmonary regurgitant area index (PRAI) was calculated from planimetric measurement of the area where PR flow was expressed. Grading of PR (1 to 3) was independently attempted according to the extension of PR flow detected in pulmonary artery by a rangegated pulsed Doppler echocardiography. PRAI (cm²/m²) was 0.36±0.29 (mean±standard deviation) in grade 1, 1.48±0.46 in grade 2, and 2.80±0.94 in grade 3. Severity of PR (grade 1 to 3) was also rated on the basis of the pulmonary arteriography and compared with PRAI. PRAI was 0.64±0.60 in grade 1, 1.07±0.63 in grade 2, and 2.21±1.67 in grade 3, respectively. RPAI showed strong correlation with pulmonary regurgitant fraction measured by videodensitometric study of right ventriculography (r=0.84). Quantitative evaluation of PR using real-time flow imaging system is a reliable and useful method.

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Long-term effects following percutaneous transluminal coronary angioplasty (PTCA) were examined using follow-up coronary angiography (CAG) in 49 lesions in cases in which the procedure was considered to be successful. Follow-up CAG was performed 2-5 times (average, 2.7 times) per patient during a period of 1 year to 3 years and 7 months (average, 1 year and 10 percentage of the value immediately after the procedure. Narrowing by 10% or more was observed in 17 lesions 3-8 months after PTCA but in only 4 lesions on the final CAG. The luminal diameter of the PTCA site was significantly greater (p<0.05) 2 years after PTCA in comparison to the findings after 1 year. These results suggest excellent long-term effects at the PTCA site.

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Real-time two-dimensional Doppler echocardiography (Doppler color flow mapping) offers useful information on valvular regurgitation. In order to quantify aortic regurgitation by Doppler color flow mapping, this study determined the relationships between regurgitant jet dimensions and angiographic grades in 100 patients, and between regurgitant jet dimensions and regurgitant fractions or regurgitant volumes in 47. Doppler data were obtained using 4 different echo windows, parasternal long and short axes, and apical two-and four-chamber views. Maximum jet area, length and diameter taken from all available views were examined in relation to angiographic grades, regurgitant fractions and regurgitant volumes. Moreover, we analyzed the technical, biological and hemodynamic factors influencing these relationships. Significant correlations were found between all maximum jet dimensions and angiographic grade (diameter, r=0.641; length, r=0.549; area, r=0.611; p<0.01). Means and standard deviations for maximum jet dimensions according to angiographic grading revealed significant differences between all grades except in jet length between grades 3 and 4. However, these relations tended to be influenced by various factors: equipment, echo window, shape of jet, coexistence with mitral stenosis or aortic stenosis, left ventricular size, left ventricular stroke volume, and diastolic blood pressure. On the other hand, m with regurgitant fractions and regurgitant volumes, maximum jet dimensions correlated well (diameter, r=0.614 and 0.567; length, r=0.769 and 0.767; area, r=0.791 and 0.773; p<0.01) when data associated with atrial fibrillation were excluded. Thus significant correlations between regurgitant jet dimensions in Doppler color flow mapping and angiographic grades can be obtained in all patients despite various factors influencing jet dimensions. Better correlations with regurgitant fractions or regurgitant volumes may be expected in patients with normal sinus rhythm.

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Coronary artery diameters were measured after various interventions in 30 patients without angina pectoris (group 1) and in 15 with angina pectoris (group 2: rest, or rest and effort angina) who had normal coronary arteries. The coronary artery diameters were significantly smaller in many coronary segments in group 2 than in group 1 during a control state, after exercise and ergonovine, but became nearly identical after isosorbide dinitrate in both groups. Patients in group 1 had diffuse narrowing but no focal vasoconstriction after ergonovine and all the segments had a diameter or more than 50% of that after isosorbide dinitrate. The change of coronary artery diameter in group 2 patients who had no vasospasm by ergonovine was the same as that in group 1. Patients in whom vasospastic angina was induced had local vasoconstriction or severe diffuse narrowing (<45%). These results indicate that angina pectoris patients with normal coronary arteries had an acceleration of coronary arterial basal tone, but vasospastic angina pectoris was not induced just by the general response of the coronary artery to various interventions in addition to the accentuated basal tone. For vasospastic angina to occur, local abnormal response to various interventions must be present.

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Eight patients with clinically stable chronic respiratory failure, hypoxemia (PaO₂&les;60 mmHg) and pulmonary hypertension (mean pulmonary arterial pressure&ges;20 mmHg) were allocated to long-term domiciliary oxygen therapy, and were followed for three months. Oxygen was supplied for from 15 to 18 hours daily from an oxygen concentrator at a flow rate sufficient to raise the PaO₂ to 60 to 80 mmHg. We examined the effects of this therapy on right ventricular performance both at rest and during exercise in these patients. Homodynamic data were obtained by right heart catheterization. Right ventricular ejection fractions (RVEF) were ascertained using first-pass quantitative radionuclide ^81mKr angiocardiography. Thirty minutes of oxygen inhalation at rest had no significant effect on cardiac function, both before therapy (T₀) and after 3 months of therapy (T₁). The mean pulmonary arterial pressure and the pulmonary vascular resistance during exercise were not significantly different between T₀ and T₁. On the other hand, at T₀, the RVEF tended to decrease from 51.6±4.9% (during oxygen inhalation at rest) to 48.7±7.9% (during exercise), whereas at T₁ it significantly (p<0.05) increased from 48.8±6.8% (during oxygen inhalation at rest) to 54.2±8.2% (during exercise). Thus, while 3 months of long-term domiciliary oxygen therapy did not reduce the right ventricular after load either at rest or during exercise, it was found to improve the right ventricular systolic performance during exercise. This suggested that long-term oxygen therapy could be useful in improving the quality of daily life of patients with chronic respiratory failure.

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The effect of the left ventricular (LV) regional wall motion during isovolumetric relaxation period (IRP) were studied in 9 patients with old anteroseptal myocardial infarction (OMI) and 8 normal subjects (NOR). There were no significant differences in heart rate, peak LV systolic pressure and peak (+) dP/dt between the groups. LV cavity was divided into the anterior and inferior sides by a long axis, which was equally divided with 3 perpendicular lines, creating 4 areas in each side. The sums of the 2 middle areas in each side were defined as Aa and Ab, respectively. During IRP the pattern of (-)dP/dt at the upstroke phase was convex-downward in OMI, but convex-upward in NOR. Time constant (T) was significantly prolonged in OMI compared with NOR (50±9 vs 37±6 msec; p<0.01). On NOR, Aa increased significantly after 33.4 msec from peak (-) dP/dt, while Ab remained unchanged. In OMI, Ab increased after 50.1 msec from peak (-) dP/dt, anterior wall by the active expansion of the inferior. Such asynchronous LV wall motions during IRP might impair LV relaxation and influence the upstroke pattern of (-) dP/dt.

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Digital subtraction angiography (DSA) was performed to evaluate graft patency in 60 patients who had undergone coronary artery bypass grafting with the internal mammary artery (IMA). Sixty IMA grafts with 62 distal anastomoses, and 84 sephenous vein grafts with 85 distal anastomoses were evaluated by intraarterial DSA with an image frequency of 4 frames/sec. A No. 4 Fr. angiography catheter was introduced percutaneously into the left brachial artery and contrast medium was injected both into the subclavian artery for specification of the IMA grafts and into the ascending aorta for specification of aortocoronary saphenous vein grafts. Bypass grafts were defined as patent when grafts were opacified through their entire course, including anastomotic sites. Fifty-nine IMA grafts with 61 distal anastomoses (98%) and 76 saphenous vein grafts with 77 distal anastomoses (91%) were patent. The overall patency rate for total grafts was 94%. In 4 patients, DSA showed a "string sign" in the IMA graft which was patent but narrowed at its distal segment. In 5 patients, large first intercostal branches were opacified. Intraarterial DSA with the retrograde brachial approach is not difficult, and is an excellent low risk method of evaluating the patency of IMA and saphenous vein grafts. DSA provided information about functional patency as well as anatomical patency of the IMA graft.

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The fate of atrial natriuretic peptide (ANP) was studied by arterial and venous catheterization in ischemic heart disease patients, and arterio-venous blood sampling in healthy kidney donors at the time of transplantation. In vitro ANP degradation was examined using healthy human plasma. In ischemic heart disease, the plasma ANP concentration at the inferior vena cava was 62.6% of that at the left ventricle, and that at the superior vena cava was 82.8%. Arterio-venous gradients were similar from pulmonary artery to vein (88.3%), from celiac artery to the hepatic vein (75.5%) and from the femoral artery to vein (85.4%). In the donor for kidney transplantation, renal arterio-venous gradient was also similar at 77.1%. No platelet consumption of ANP was noted, and the molecular forms of ANP present in the circulation were similar in samples obtained from both the coronary sinus and the superior or inferior vena cava. We conclude that no specific organ plays a dominant role in ANP degradation, and that ANP molecular forms may not be altered during circulation.

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The effect of superoxide dismutase (SOD) on the size of the myocardial infarct resulting from various durations of ischemia and a 72-hour reperfusion was examined in the rabbit. A coronary branch of the circumflex artery was occluded for 20, 30, or 60 min and then reperfused. Seventy-two hours after the coronary occlusion, the infarct size and the size of the area at risk (viscular bed of occluded coronary artery) were determined by histology (hema-toxylin-eosin and Mallory's staining) and by fluorescent particles, respectively. Human SOD (45, 000 units/kg) was injected intravenously as a bolus in SOD-treated rabbits, while only saline was administered to control rabbits. The percentage of the area at risk which actually infarcted (%I/AAR) was 25.5±12.9% (mean±S.D.) in the 20-min ischemia control group (n=9), 19.7±10.2% in the 20-min ischemia SOD group (n=9), 41.0±6.3% in the 30-min ischemia SOD group (n=9), 74.2±13.8% in the 60-min ischemia control group (n=9), and 76.6±8.2% in the 60-min ischemia SOD group (n=7). The %I/AAR was not significantly different between the control and SOD groups for any duration of ischemia. Heart rate, blood pressure, and the size of area at risk were comparable in all six groups. These findings suggested that oxygen-free radicals produced during initial moments of reperfusion were unlikely to contribute to myocardial necrosis regardless of the duration of ischemia in the rabbit.

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Recent extensive studies suggested that some humoral factors may contribute to the development and/or reversal of cardiac hypertrophy in hypertension. The purpose of this study is to examine whether there exists humoral factor(s) for cardiac hypertrophy in experimental perinephritic hypertension in dogs. Hypertension was induced by the method of Page with some modifications. Humoral factors were studied using a microassay system that was independent of pressure overload, hemodynamic effects, and other factors. L(-)-isoproterenol (ISO) and angiotensin II (AngII) increased the uptake of ³H-uridine into 10-day-old cultured heart cells. The maximal response to ISO or AngII was obtained by 10^-5 M ISO or 10^-10 M AngII, and the percent increments in the uptake of ³H-uridine was 38.4±20.4%, and 45.1±22.5%, respectively. Moreover, ISO, DL-noradrenaline, and AngII stimulated protein synthesis of 7-day-old or 14-day-old cultured heart cells in this order (9.5±1.5, 7.3±1.2, 2.0±0.5μg/6×10⁵ by 7-day-old heart cells; 23.8±8.3, 19.0±9.4, 4.4±1.1μg/6×10⁵ by 14-day-old heart cells). Heart and kidney extracts were obtained from experimental perinephritic hypertensive dogs and sham-operated dogs. The heart extract obtained from hypertrophied left ventricle (LV) of the experimental hypertensive dogs, but not of the sham-operated dogs, increased the uptake of ³H-uridine into 10-day-old heart cells. The mean percent increment in uptake of ³H-uridine induced by the hypertrophied LV heart extract at a final concentration of 5×10^-3% V/V (1-3μg) in different experiments was about 15%. High performance liquid chromatography (HPLC) demonstrated that the LV heart extract obtained from the perinephritic hypertensive dogs contained at least 16 molecules. Among them, one with a molecular weight of approximately 11, 200 daltons stimulated uptake of both ³H-uridine and ¹⁴C-leucine into cultured heart cells.

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We report a case of a 37-year-old woman who had paroxysmal ventricular tachycardia (VT) during early pregnancy. She had severe hyperemesis, palpitation at 6 weeks of gestation and many episodes of paroxysmal VT, but no apparent organic heart disease. At that time she had a transient increase of thyroid hormone levels. With bed rest and without medication, hear symptoms and episodes of VT disappeared in accordance with the improvement of hyperemesis and thyrotoxicosis. She demonstrated a rare course of arrhythmias in which the deterioration of VT was observed at transient thyrotoxicosis and hyperemesis.

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Excessive catecholamine levels can cause myocardial damage in experimental animals. Similar observations have been made in humans following autopsy for pheochromocytoma. However, whether catecholamine crises are reversible or not remains uncertain. We report here a case in which pheochromocytoma manifested as acute pulmonary edema during an operation. Serial echocardiograms revealed that the depressed motion of the left ventricular wall was reversed after tumor removal. The plasma catecholamine level was extraordinarily high during the episode of acute pulmonary edema, and it seems that catecholamines in high concentration can directly damage the myocardium.

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No aneurysm of the aortic valve associated with infective endocarditis has yet been reported. This report describes the clinical echocardiographic and pathologic findings in a patient who developed infective endocarditis resulting in aneurysm of the non-coronary cusp with aortic regurgitation. Surgical treatment was performed because of gradual expansion of the aneurysm and gradual thinning of its wall. Two-dimensional and color Doppler echocardiographies proved useful for the initial diagnosis and serial follow-up of this unusual case and for its successful surgical management.

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