In order to understand the mechanism of development asymmetric septal hypertrophy (ASH) in hypertension, 290 patients with essential hypertension (HT) were examined echocardiographically. Out of them 84 cases of advanced left ventricular hypertrophy (LVH) [37 cases of symmetric hypertrophy (HT-SH group) and 47 cases of ASH (HT-ASH group)] were compared in their clinical and echocardiographic findings with hypertrophic cardiomyopathy (HCM). In the 290 HT cases, the highest systolic pressure in each patient's history was found to correlate with left ventricular (LV) posterior wall thickness (PWT), but not with the septal wall thickness (IVST). There were no differences in LV thickness (IVST+PWT) among patients in the HT-ASH, HT-SH and HCM groups. While the HCM group patients showed no significant differences in IVST and PWT from those in the HT-ASH group, they did have greater IVST and smaller PWT than HT-SH group patients. The rapid filling rate (RFR) was also not much different in the HCM and HT-ASH groups, but was significantly lower in the HCM group than in the HT-SH group. Furthermore, HT-ASH group patients has a milder degree of hypertension and a higher incidence of familial occurrence of HCM than did those in the HT-SH group. After treatment for HT, the HT-SH group showed a significant decrease in wall thickness during long-term observation, while the HT-ASH and HCM groups, failed to exhibit such changes. Moreover, the degree of myocardial disarrangement in the HT-ASH group did not differ significantly from that in the HCM group. These results suggested that LVH in HT is related not only to pressure load but also to genetic factors similar to that in HCM.

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It is thought that a hypercoagulable state contributes to the pathogenesis of coronary artery disease (CAD), but few sensitive markers have been available for detecting the state. In the present study the plasma level of thrombin-antithrombin III complex (TAT), a specific indicator of thrombin generation in blood, was investigated before and after a submaximal exercise test in 18 patients with CAD and in 12 healthy controls. The mean (±SEM) value of plasma TAT before the exercise was 3.30 (0.81) ng/ml in the patient group and 1.49 (0.08) ng/ml in controls, and its level increased to 29.22 (5.74) ng/ml and 12.07 (2.89) ng/ml after the exercise, respectively. Thus, the TAT value in the patient group was higher than that in the controls both before and after the exercise. However, no differences could be found between the groups in the following parameters; prothrombin time, activated partial thromboplastin time, antithrombin III, fibrinogen, FDP, plasminogen, α₂-plasmin inhibitor, and α₂-macroglobulin. Through these results it was concluded that plasma TAT level could be a sensitive marker for latent activation of blood coagulation, and also that the results of these experiments showed that patients with CAD were in a latent hypercoagulable state.

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To clarify factors which have an influence on late potentials (LPs), signal averaged electrocardiogram, echocardiogram, cardiac catheterization and Holter monitoring were studied in 86 patients with previous myocardial infarction (MI). Group 1 consisted of 27 patients with LPs (LP duration&ges;20 msec) and Group 2 consisted of 59 patients without them. Twelve percent of anterior MI and 35% of inferior MI had LPs. Left ventricular (LV) diastolic dimension was larger and % fractional shortening was lower in group 1 than those in group 2. Aneurysm was noted in 37% in group 1 and 17% in group 2 (p<0.05), and mean number of involved coronary vessels was 2.3±0.8 in group 1 and 1.7±0.8 in group 2 (p<0.05). No significant difference was found in other clinical and hemodynamic parameters. The incidence of patients with 100 or more ventricular premature contractions per hour and that with ventricular tachycardia (VT) were significantly higher in group 1 than in group 2 (26% vs 7%, p<0.05, 33% vs 7%, p<0.01, respectively). Multiple regression analysis and the method of quantification demonstrated that ventricular arrhythmia was most strongly associated with LP duration.

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Sixteen of 75 patients with dilated cardiomyopathy (DCM) died during a mean follow-up period of 39.7 months. In non-survivors, the cardiothoracic ratio and the left ventricular end-diastolic dimensions were greater, the left ventricular end-diastolic pressures were more elevated, and the cardiac index was lower than in the survivors at the time of initial diagnosis. There were no significant differences between survivors and non-survivors in the magnitude of the maximum QRS and T vectors or in the maximum T angle. In the non-survivors, the maximum QRS vector was directed more posteriorly and the width/length ratio of the loop in the horizontal plane was smaller than in survivors or showed bizarre figure-of eight configuration. It appears than in DCM a marked posterior displacement of a QRS loop that is narrow and distorted or is in a bizarre figure-of eight configuration in the horizontal plane indicates and unfavorable prognosis.

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A modified thermodilution technique was used to determine the quantity of shunt in patients suffering from congenital heart disease with a left to right shunt. In our modification, the thermistor was placed within the pulmonary artery and an indicator was injected into both sides of the heart. In a series of 33 cardiac catheterizations in children (1-17 years) with ventricular septal defect (VSD), pulmonary blood flow (Qp), systemic blood flow (Qs) and the ratio of Qp to Qs (Qp/Qs) were determined by this and ordinary oximetry (Fick) methods. Correlation coefficients between indexes obtained by these methods were 0.54 (Qp), 0.78 (Qs), and 0.75 (Qp/Qs). The estimates of Qp and Qp/Qs obtained by thermodilution were smaller than those obtained by the Fick method. This modification of thermodilution is simple, rapid, and useful in clinical practice.

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Total exchangeable sodium (Nae), potassium (Ke), and total body water (TBW) were measured by the multiple isotope dilution method, in 10 healthy subjects (normal), 10 patients with congestive heart failure (CHF), and 47 patients with acute myocardial infarction (AMI), 1-2 months after onset. According to Killip's classification, 29 patients with AMI were classified as class I, and 18 patients were classified as class II and III (referred to as class II & III). No differences were found in plasma and urine sodium and potassium concentrations. By the multiple isotope dilution method, significant elevations in Nae/BSA (body surface area) were observed in the following order: normal, class I, class II & III and patients with CHF. Compared with normal subjects, Nae/Ke and Nae/Ke were elevated in class I patients. Elevations of Nae/Ke and TBW/BSA in both class II & III patients with AMI and patients with CHF indicated severe cardiac impairment. Both Nae/BSA (p=-0.60) and Ke/BSA (p=0.71) had negative and positive correlations with the left ventricular ejection fractions (EF) measured by catheterization in 20 patients with AMI. This indicates a major sodium and water retention mechanism due to impaired cardiac function in AMI. It is worth noting that conspicuous abnormalities in body fluid compositions, particularly in class I patients with AMI as well as class II & III, remained despite no evidence of cardiac failure.

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To elucidate the metabolic properties of the heart of spontaneously hypertensive rats (SHR), we examined the uptakes of ³H-uridine (3H)and ¹⁴C-leucine (14C) into single cultured heart cells, as well as the total protein content and cell size of heart cells in the presence and absence of stimulation, and compared the findings with those obtained with Wistar Kyoto rat (WKY) cells. As a result, (1) Spontaneous uptakes of 3H and 14C into WKY heart cells increased rapidly from day 2 to days 5-6, and then decreased gradually. In contrast, in SHR heart cells a constant increase in the uptakes of 3H and 14C was observed until the 10th day. The uptakes of both 3H and 14C into 10-day-old SHR heart cells were significantly higher than those into WKY heart cells (p<0.05). (2) The total protein content of SHR heart cells cultured for 4 or 5 days was significantly less than that of WKY heart cells, but there was no significant difference between cells cultured for more than 6 days. As for cell size, no significant difference was observed regardless of how long the cells were cultured. However, the increment in SHR heart cell total protein and cell size during cultivation appeared to be higher than they were in WKY heart cells. (3) Stimulation of heart cells with 10^-8-10^-5 M L(-)-isoproterenol (ISO) for 1 hour increased the uptake of 3H into heart cells from both kinds of rats, with no significant difference between the two. In contrast, after 3-hour stimulation uptake of 3H into WKY heart cells was lower than it was after a 1-hour stimulation, while that in SHR heart cells increased. Angiotensin II (AngII) also increased the uptake of 3H into both types of heart cells, the responsiveness to various concentrations of AngII showing no significant differences. Our results showed that SHR heart cells in vitro had an increased spontaneous metabolic rate and an increased responsiveness to ISO, confirming previous in vivo results and suggesting that these metabolic properties play a role in cardiac hypertrophy in SHR.

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The effect of vitamin E on the ventricular fibrillation threshold was studied in an experimental model of acute myocardial ischemia. An anterior thoracotomy was performed on 23 anesthetized Wistar rats. The ventricular fibrillation threshold was measured. Vitamin E was then administered intravenously to an experimental group (n=11) and a placebo to a control group (n=12). The ventricular fibrillation threshold was measured again. FInally, the left anterior descending coronary artery was occluded, producing antero-apical myocardial ischemia. The ventricular fibrillation threshold was measured again. This threshold did not very significantly when vitamin I or the placebo was administered before occluding the coronary artery but after the occlusion a threshold decreased in the placebo group was observed, whereas no such decrease was manifested in the vitamin E-treated group. The results suggest that vitamin E prevents ventricular fibrillation in acute myocardial ischemia in rats.

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To clarify the effects of right ventricular (RV) pressure overload on functional and geometrical interference and interdependency between the right and left ventricle, both ventricular internal diameters were measured by the microcrystal technique during lycopodium induced pulmonary embolization in the dog. By repeated embolization, RV systolic pressure was increased progressively until it reached a peak value of about 60-70 mmHg, then it began to fall. At the same time, the hemodynamics deteriorated progressively resulting in death. During the experiment, gradual leftward displacement of the interventricular septum (IVS) without any change in left ventricular (LV) free wall geometry was observed. In pulmonary embolic shock, which shoed a fall in LV pressure to about 60 mmHg and cardiac output to about 40% of control, the leftward displacement of IVS became marked, and the cooperative movement of IVS to LV contraction disappeared. The IVS position during acute RV pressure overload was able to account for the trans-septal pressure gradient. The importance of IVS position and motion in cardiac function during acute RV pressure overload was stressed. Furthermore, to establish the theoretical treatment in acute cardiopulmonary resuscitation, ligation of the descending aorta (AoL) or norepinephrine ("N") or isoproterenol ("I") administration were examined in a canine pulmonary embolic shock model. AoL or "N" improved the deteriorated hemodynamics with restoration of biventricular geometry. However, "I" did not restore the biventricular geometry despite the transiently improved hemodynamics, and the experimental animals were unable to survive. These results suggest the importance of the maintainance of systemic pressure for the restoration of failed RV function. Further integrated studies are required to understand biventricular interference and interdependency.

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Thirty autopsied hearts with cor pulmonale and 20 experimental pulmonary hypertensive rat hearts were analysed macrosopically and hitometrically. In autopsied hearts with cor pulmonale, right ventricle dilatated in oblique length, and right ventricular wall thickness significantly increased at pulmonary conus (PC) and posterior wall of right ventricle (RVP) compared with that at anterior wall of right ventricle (RVA). Mean diameters of myocardial fibers at PC, RVP, right ventricular side of interventricular septum (IVR) and mid layer of interventricular septum (IVM) significantly increased compared with that at mid layer of left ventricular wall (LVM). The wet weight and the diameter of myocardial fibers in right ventricle (RV) significantly correlated with those in interventricular septum (IVS). In pulmonary hypertensive rats, wet weights of RV and IVS increased significantly with the elevation of mean pulmonary arterial pressure. The diameters of myocardial fibers increased at RVP, RVA, IVR and IVM. There was no significant cardiac hypertrophy in left ventricle (LV), either microscopically or macroscopically. These results suggest that IVS responded morphometrically rather than inconcord with RV but not with LV the cor pulmaonade heart.

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To clarify how left ventricular pumping action is altered in cor pulmonale, and experimental study was performed using canine heart preparations in which the effects on left ventricular performance of right ventricular overload, with and without depressed systolic function, were investigated. For this purpose, two methods using excised perfused hearts (n=16) and in vivo hearts (n=6) were employed, and in the latter condition, pulmonary artery constriction (n=7), femoral arterial-venous (A-V) shunt (n=3) and right coronary artery occlusion (n=6) were induced. Left ventricular systolic function was assessed by the relationship between left ventricular isovolumic developed pressure and left ventricular volume in excised heart, and by ejection fraction with 2 dimensional echocardiogram in the in vivo condition, taking into account preload and after load changes. From the excised heart preparation, it was shown that left ventricular developed pressure significantly decreases when right and left ventricular diastolic pressure increases greatly. On the other hand, in vivo right ventricular overload due to pulmonary constriction and A-V shunt, the left ventricular ejection fraction increased following afterload reduction. When we compare the left ventricular ejection fraction in pulmonary constriction with that in right coronary occlusion, in which reduction of left ventricular diastolic area from the control was similar, the latter was significantly decreased despite afterload reduction. These results suggest that right ventricular overload does not necessarily induce left ventricular systolic dysfunction unless left ventricular end-diastolic pressure, as well as that of the right ventricle, increases definitely and simultaneously. They also suggest that right ventricular overload with right ventricular systolic dysfunction, clinically found in cor pulmonale, may induce left ventricular systolic dysfunction concomitantly.

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To formulate right ventricular (RV) mechanical and energetic properties in terms of the time-verying elastance model, Emax and the systolic pressure-volume are (PVA) of RV were measured in the excised cross-circulated heart preparation, while the left ventricle was beating unloaded. Emax of RV was constant, and independent of the RV volume, the stroke volume, the ejection velocity, and the pre-ejection period in the control contractile state. Enhancement of the contractile state with calcium increased Emax, and reduction of the contractile state with propranolol decreased Emax. The whole heart oxygen consumption (Vo₂) was linearly regressed on PVA of RV, in both the control and the calcium-enhanced contractile state. Calcium elevated the regression line in a parallel manner. The slope of the regression line was (1.85±0.19)×10^-5 ml O₂/mmHg ml in the control state, and (1.57±0.44) in the calcium state. These slope values were similar to those in left ventricle (LV). We there fore conclude that mechanical and energetic properties of RV are similar to those of LV.

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Many investigators have reported the hemodynamics in acute cor pulmonale clinically and experimentally. However, earlier studies have not made quantitative evaluations of the effects of coronary perfusion pressure and hypoxia on right ventricular contractility. We simulated acute cor pulmonale in nine isolated canine hearts and investigated the relationship of the process to cardiac deterioration and restoration. The afterload and preload of the right ventricle were controlled with a computer-assisted load control servosystem. Coronary perfusion pressure (COPP) was also controlled at either normal or variable levels identical to products of measured cardiac output and assumed valued of systemic vascular resistance. Critical state (CS) was defined as a condition with an initial decrease in peak systolic pressure despite increased afterload. Within the normal range of PaO₂ (105±5.3 mmHg), CS developed at a COPP of 51±5.1 mmHg, while under low Pa O₂ (51±2.3 mmHg), it developed at a COPP of 59±8.8 mmHg. As long as the COPP was normal (90 mmHg), the contractility of the right ventricle did not decrease despite hypoxia (PaO₂ 51±2.3 mmHg). An increase in systemic vascular resistance or administration of a beta-stimulant at CS restored the contractility of the right ventricle. However, and increase in preload decreased the contractility of the right ventricle.

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Twenty-eight patients with chronic pulmonary diseases were examined with standard 12-lead electrocardiogram (ECG), vectorcardiogram (VCG), and body surface ECG mapping (MAP). The electrocardiographic findings were compared with results of 99 mTc radionuclide right ventriculography or T1-201 myocardial scintigraphy. In a stepwise multiple regression analysis between the electrocardiographic parameters and right ventricular ejection fraction, only the amplitude of the negative P wave in V2 (r=0.69), the posterior force of P loop in VCG (r=0.71), and the size of -2SD area at 50 msec QRS potential departure map (r=0.55) were selected as the parameters in standard ECG, VCG, and MAP, respectively. On the radionuclide ventriculography and myocardial scintigraphy, 14 patients were judged to have right ventricular overload. The criteria by VCG, and MAP had better sensitivity and specificity for right ventricle overload than those by 12-lead ECG. VCG criteria of Chou et al had sensitivity of 93% and specificity of 71%. MAP criteria, departure index of F3 or F4≤-2, had sensitivity of 86% and specificity of 79%. The electrocardiographic findings by standard 12-lead ECG, VCG and body surface ECG mapping are useful parameters for the non-invasive detection of right ventricular overload in patients with chronic pulmonary diseases.

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133 patients with chronic cor pulmonale due to dysventilation syndrome were studied. Chronic obstructive pulmonary disease (COPD) was found, possibly for the first time in Japan, to be the most common etiological condition, occurring in 54% of the patients. Chronic cor pulmonale was clinically diagnosed as the appearance of right heart failure on admission. Patients were divided into two groups depending on clinical state, compensated and decompensated. There was a marked difference in arterial blood gases and electrocardiographic fluctuations between the states. Serial observations of these parameters and enlarged cardiac silhouette to the left on plain chest film provided diagnostic evidence for development to the decompensated state. Pulmonary artery pressure changes on exercise and during sleep at night has been considered to impair right heart function. Prognosis of chronic cor pulmonale largely depends on the concentrated therapy of the decompensated state with active intensive therapy. Recent therapeutic progress has made control of this serious disease possible, despite the appearance of right heart failure. Laborious prolonged therapy appears to be essential in order to improve long-term prognosis.

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133 patients with chronic cor pulmonale due to dysventilation syndrome were studied. Chronic obstructive pulmonary disease (COPD) was found, possibly for the first time in Japan, to be the most common etiological condition, occurring in 54% of the patients. Chronic cor pulmonale was clinically diagnosed as the appearance of right heart failure on admission. Patients were divided into two groups depending on clinical state, compensated and decompensated. There was a marked difference in arterial blood gases and electrocardiographic fluctuations between the states. Serial observations of these parameters and enlarged cardiac silhouette to the left on plain chest film provided diagnostic evidence for development to the decompensated state. Pulmonary artery pressure changes on exercise and during sleep at night has been considered to impair right heart function. Prognosis of chronic cor pulmonale largely depends on the concentrated therapy of the decompensated state with active intensive therapy. Recent therapeutic progress has made control of this serious disease possible, despite the appearance of right heart failure. Laborious prolonged therapy appears to be essential in order to improve long-term prognosis.

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The flow reserve of the right coronary artery (RCA) and myocardial oxygen extraction are important tractors in any investigation of the mechanisms of impaired right ventricular function. The present study induced brief coronary occlusions and examined the effect on right coronary blood flow in normal dogs, and the effect on myocardial oxygen metabolism in dogs with right ventricular hypertrophy (RVH). Right coronary flow reserve, represented by occlusion duration causing a half maximum dilatation (T1/2), was greater in the RCA than in the left anterior descending coronary artery of normal dogs; 11.3±2.3 sec vs 5.9±1.4 sec. Myocardial oxygen extraction ratio (EO₂) of the right ventricle (RV), 51.3±1.6%, was significantly (p<0.05) lower than the index of the left ventricle (LV), 60.6±1.0%, and the extraction of the RV increased significantly in association with an increase of myocardial oxygen demand. In dogs with RVH caused by chronic banding of the pulmonary artery, this dominant oxygen reserve was lost: the EO₂ of the hypertrophied RV was high compared with the EO₂ of the normal RV (57.3±3.4% vs 51.3±1.6%, p<0.05), and no further increase in EO₂ was observed in the hypertrophied RV in response to the elevation of the myocardial oxygen requirement. Oxygen usage per 100g of the RV for a certain level of overall RV work, rate-pressure product, was significantly (p<0.02) lower in the hypertrophied RV (0.00054 mlO₂/beat·mmHg) than in the normal RV (0.0012 mlO₂/beat-mmHg). These \findings suggest that the normal RV had the dominant reserve of oxygen supply through both the greater capacity of flow increment and ability to increase oxygen uptake from blood. This advantage was lost in the hypertrophied RV, but improved oxygen efficacy to overall RV mechanical work would contribute to maintain the normal function in the hypertrophied RV.

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In patients with chronic lung disease, we estimated the effectiveness of nocturnal oxygen therapy in eliminating episodes of sleep hypoxemia and concomitant elevations in the pulmonary arterial pressure. We also assessed the effect of vasodilators (ISDN, nifedipine) in improving exercise tolerance. Our results support the efficacy of nocturnal oxygen therapy. Visodilators examined were not confirmed as effective or safe for wide use.

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