In addition to our previous reports which are based on the work of the Japanese Sarcoidosis Committee, this communication reports the analysis of expanded case material, evaluation of endomyocardial biopsy in 8 biopsied and 7 autopsied cases, and the effects of steroid and pacemaker therapy. 1. Out of 96 autopsied cases of sarcoidosis, 55 cases have been determined by us as being fatal myocardial sarcoidosis. Additionally, analysis of sarcoidosis patients who were clinically assessed as having cardiac dysfunction was made through the literature and in 17 cases a questionnaire review of the reported cases in Japan was made. It was noted that out of a total of 72 cases, there was a high incidence of cardiac sarcoidosis (fatal myocardial sarcoidosis + sarcoidosis with cardiac dysfunction) in 40-59 year-old women. 2. The modes of cardiac death in fatal myocardial sarcoidosis in 55 cases were: sudden death 20 cases (36.4%); congestive heart failure 10 cases (18.2%); arrhythmia 9 cases (16.4%): Adams-Stokes Syndrome (except sudden death) 8 cases (14.5%); cardiogenic shock 1 case (1.8%); pacemaker death 1 case (1.8%); pulmonary infarction 1 case (1.8%) and unknown 5 cases (9.1%). 3 . Expectancy of a definite diagnosis of endomyocardial biopsy which was made by an imitation endomyocardial biopsy in 7 autopsied cases of fatal myocardial sarcoidosis was 62.8% from the right ventricle and 46.9% from the left ventricle. When such pathology as a distinct scar or acute inflammatory change is incorporated, the possibility of the usefulness of the biopsy increases. Examples of 8 biopsied cases were shown. 4. Ultrastructural findings of epithelioid cells and giant cells in a case of a 42-year-old female in whom endomyocardial biopsy was performed from the right ventricle were described. 5. Our view on the nature of giant cell myocarditis was discussed. This is not a disease entity but a histopathological entity. 6. Evaluation of steroid therapy in cases with fatal myocardial sarcoidosis and with cardiac dysfunction revealed that it was effective in 5 out of the 14 cases of the former group (35.7%), and 10 out of the 14 cases of the latter group (71 .4%). 7. Pacemaker implantation, either temporary and/or permanent, was made in 9 of the 55 cases (16.5%) of fatal myocardial sarcoidosis and in 6 of the 17 cases (35.5%) of sarcoidosis with cardiac dysfunction. In the former group, the pacemaker was effective for a certain period of time but finally death occurred. In the latter group, pacemaking was effective.

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Through an approach employing endomyocardial biopsy, early diagnosis of acute idiopathic myocarditis is possible. The histopathological findings consisted of fragmentation of muscle bundles, degenerative changes with lysis of myocytes and interstitial mononuclear cell infiltration. The cells were irregular in size and shape and contained slightly basophilic cytoplasm or were mixed with small round cells. Early clinical symptoms consisted of flulike symptoms, i. e., higher fever, myalgia, malaise and arthralgia. Initial ECG changes consisted of complete A-V block in 9, bifascicular block in 3, and intraventricular conduction disturbance in 4 cases. Serial biopsies were performed at the early (0-2 weeks), middle (2-4 weeks), and late stages (more than 4 weeks) in 6 cases. Two of these biopsies were performed in 6 cases and all 3 were performed in one case. The numerous interstitial cell infiltration had almost disappeared by the early stage. At the late stage, either a slight or moderate degree of interstitial fibrosis was observed. These observations coincided well with the improvement of the ECG findings. Characteristic laboratory findings consisted of high LDH, GOT, and serum amylase levels. Varieties of treatments such as temporary cardiac pacing, peritoneal or hemo-dialysis, vasodilator therapy effectively to relieve the grave clinical condition. It is concluded that acute myocarditis may heal with remarkable improvement when the appropriate treatment is applied at the early stage of the disease.

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Human renin substrate (angiotensinogen) was purified from outdated bank plasma. Purification procedures included ammonium sulfate precipitation, DEAE-cellulose column chromatography, concanavalin A-Sepharose column chromatography, Hydroxylapatite column chromatography preparative isoelectric focusing and Ultrogel AcA 44 gel filtration. The final recovery was 10% and the specific angiotensin I content of 10.5 μg/mg of protein was obtained. Polyacrylamide gel and SDS-polyacrylamide gel electrophoresis and analytical ultracentrifugal analyses showed the homogeneity of the purified renin substrate. The molecular weight of 60900 was determined by sedimentation equilibrium studies. Human renin substrate was a glycoprotein containing 13% carbohydrate. Cystine could not be detected on amino acid analysis. The purified renin substrate showed the isoelectric point heterogeneity (pI, 4.6 and 4.9).

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To study the pathophysiology and the pathogenesis of hypertensive cardiac diseases such as cardiac hypertrophy and ischemic heart diseases, and to determine the relationship between these cardiopathies, spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) were used as models. Vectorcardiography was applied to the rat according to orthogonal Takayasu lead system and "vectorcardiography for small animals" with a good reproducibility was established. Characteristic vectorcardiogram (VCG) was obtained from 5-month-old SHR, compared with normotensive Wistar-Kyoto rats (WOK). Left superior (posterior) deviation of QRS vector usually with ST-T changes was recognized as LVH (Left Ventricular Hypertrophy) pattern of SHR and such corresponded to the pathological findings of the increased heart weight and the increased weight and thickness of the left ventricular wall, and also to the high blood pressure. Macroscopical morphological features of the heart were also studied. Chest roentgenography showed an increased cardiothoracic ratio (CTR) and the protrusion of the left ventricular portion in the posteroanterior cardiac silhouette of SHR. The horizontal view of the chest, cross-sectioned by the apparatus of whole body autoradiography, PMV-cryomicrotome 450 MP, indicated the left anterior orientation of the interventricular septum in rats, as is the case in humans, and the clockwise rotation of the left ventricular cavity in SHR, compared with WK. The coronary arterial wall thickening with narrowed lumen was noted even in the prehypertensive 1-month-old SHR. Such correlated well with the wall thickening of the left ventricle . From these vectorcardiographical and morphological studies on SHR and SHRSP, genetic hypertension was ascertained to be significant not only for cardiac hypertrophy but for the coronary arterial wall thickening, both of which may also enhance the myocardial lesions in SHR, particularly in SHRSP.

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The functional capacity of coronary collaterals was investigated under resting and stress conditions in 15 dogs with chronic occlusion of the anterior descending coronary artery. ST-elevation in epicardial and intramyocardial electrograms was used for assessing the degree of regional myocardial ischemia. In resting condition, epicardial and intramyocardial electrograms from collateral intermediate and circumflex areas revealed no significant ischemic changes. In 6 of 15 dogs in which atrial pacing was performed, ST-elevation appeared in electrograms from collateral and intermediate areas. In another 9 dogs, pacing tachycardia produced no significant changes in all electrograms. In these dogs more than 50% constriction of the donor coronary artery was necessary to induce ST-e1evation in electrogram from collateral area. These findings indicate that the coronary collateral vessels in dog play beneficial role to prevent the myocardium from ischemic injury under stress condition, although their functional capacity is not comparable to that of normal coronary artery.

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It was researched how the ECC affects on cardiac performance and the total and regional coronary blood flow, using two groups of dogs with a hypertrophied heart and a non-hypertrophied heart, each group of which was further divided into two subgroups depending on whether the intermittent 40 mins. anoxic arrest was applied or not. Cardiac performance before and 60 mins. after cessation of ECC were compared each other. Coronary hemodynamics was studied before, during (immediately before and after anoxic arrest), and 60 mins. after cessation of ECC, using 15±5 diameter radioactive microspheres. 1) In the group of a non-hypertrophied heart, no obvious changes of cardiac performance were seen before and after ECC. The total coronary blood flow increased after ECC than before. Though the regional coronary blood flow pattern showed no differences in this group except only immediately after anoxic arrest, when the regional blood flow into the right ventricle, inner and middle layers of the left ventricle increased. 2) In the group of a hypertrophied heart, cardiac performance decreased after ECC, and further significant decrease was observed in the subgroup of anoxic arrest. No significant changes of the total coronary blood flow were observed before and after ECC in this group, even when compared with that in the group of a non-hypertrophied group. However, the increase of blood flow to the right ventricle, inner and middle layers of the left ventricle immediately after anoxic arrest was not oberved, that was seen in the group of a nonhypertrophied heart. 3) It follows that the decrease of cardiac performance after ECC in the group of a hypertrophied heart is not due to the changes of the total and regional coronary blood flow. It is considered that the difference of the regional coronary blood flow pattern changes immediately after anoxic arrest between the non-hypertrophied heart group and hypertrophied group may cause the different changes of cardiac performance before and after ECC between the two groups. This consideration should be more justified by evaluating not only coronary hemodynamics but also the relationship between cardiac metabolic needs and the regional coronary blood flow.

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The clinical evaluation of β-adrenergic receptor blocker acebutolol in anaesthesia was done and following results were obtained. 1) Acebutolol resembles practolol in potency but has a more modest degree of cardioselectivity. 2) Antiarrhythmic action is excellent. A seventy-three percent cure ratio was obtained with the first dose of 3 7.4μg.kg^-1. This dose is the second largest dose to the dose of practolol among 10 β-adrenergic receptor blockers which were studied by the authors in order to obtain the same effect. The maximum dose required reached 250μg.kg^-1 in one case. The final cure ratio of arrhythmia was 96%. Preventive effects on epinephrine-induced arrhythmia are sufficient. 3) Antitachycardiac action is moderate. The cure ratio of tachycardia from the first dose of 37.2μg.kg^-1 was 88%. The maximum dose required reached 80 μg.kg^-1 in one case. The heart rate in all cases was successfully reduced by 18.6%. The effect of the drug appears fast and therefore can be effective in treating tachycardia during anaesthesia. 4) Systolic, diastolic, and mean arterial pressure decreased moderately. Pulse pressure decreased considerably. Decrease of stroke volume was a minimum, but cardiac output decreased 20%. Decrease of cardiac work and Katz's index indicate reduced myocardial oxygen consumption. Total peripheral resistance increased. 5) Cardiovascular depression by 37.3μg.kg^-1 of acebutolol is milder than those of 45μg.kg^-1 of practolol which is considered as equipotent. When a dose less than 40 μg.kg^-1 of acebutolol is administered, cardiovascular depression is not serious in a severely damaged myocardial case. 6) No complication was noted in asthmatic or emphysematous patients when acebutolol is used in a small fractional dose. Twenty μg.kg^-1 will be safe. The authors' study suggests that acebutolol has a cardiovascular selectivity, and is effective as an antiarrhythmic and antitachycardiac agent in a patient under anaesthesia with safety.

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