Prognosis of 36 patients with congestive cardiomyopathy was studied in relation to various clinical factors. Half life of the survival curve after overt heart failure was about 7 years. Although left ventricular function was a major determinant of clinical course in congestive cardiomyopathy in general, its relation to prognosis was variable according to the type of cardiac involvement. In peripartal cardiomyopathy and in a type of cardiomyopathy named subacute cardiomyopathy with pulmonary thrombosis in this paper, factor(s) other than left ventricular function, possibly including pulmonary thrombosis, may be operative as more important determinant of extremely poor prognosis in these subtypes. Alcoholic cardiomyopathy was also unique in its favorable prognosis in association with reversible cardiomegaly following abstention from alcohol.

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The morphology of the externally recorded carotid pulse tracing was studied in 33 patients with valvular aortic stenosis for indices of severity. Comparisons were made with 10 normal controls. In aortic stenosis, initial upstroke time (IUT) of the carotid pulse, and left ventricular ejection time index were significantly higher and the rate of rise of the carotid pulse was slower than in the control group. Severity of stenosis (calculated valve area and mean pressure gradient) could not be predicted, however, from any of these indices. The IUT of the carotid pulse did correlate well with mean velocity of circumferential fiber shortening (mVcf) (r=-0.72). The rate of rise of the carotid pulse had also a correlation with mVcf (r=0.66). However, other commonly used hemodynamic indices (cardiac index, systemic vascular resistance, stroke volume, and ejection fraction) did not have a good correlation with IUT and rate of rise of the carotid pulse.
These results suggest that we are able to separate by carotid pulse tracings aortic stenosis from normal subjects, but we cannot say what is the degree of severity of aortic stenosis from analysis of the external carotid pulse recording.

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The effects of verapamil, a slow channel blocker and a potent antiarrhythmic drug, on retrograde V-A conduction were investigated following diagnostic cardiac catheterization in 12 children premedicated with lytic cocktail. Surface EKG, intra-atrial and His bundle electrograms, as well as right ventricular pacing with use of extra stimulus technique were obtained before and after a single intravenous dose of verapamil (0.15mg/Kg, max 5mg). Verapamil prolonged the AH interval in 9/12 and abolished or prolonged the retrograde V-A conduction whenever present (abolition in 5/12 and prolongation in 1/12). The duration of retrograde V-A conduction exceeded the antegrade conduction time in all. It is concluded that verapamil abolishes retrograde V-A conduction whenever present and this phenomenon may further explain the antiarrhythmic effects of the drug on retrograde conduction dependent (reentrant) arrhythmias.

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Disopyramide has been successfully used to treat a variety of supraventricular and ventricular arrhythmias. The electrophysiologic effects of this drug were studied following diagnostic cardiac catheterization in 14 children aged 7 months to 14 years, suffering from congenital heart disease. Surface EKG, intra-atrial, and His bundle electrogram as well as right atrial pacing with the use of extrastimulus technique were obtained before and after a single intravenous dose of disopyramide (2mg/Kg, max 50mg). The drug significantly prolonged the HV interval, effective and functional refractory periods of the atrium and the AV node. The most consistent change was the prolongation of the atrial refractory periods. The electrophysiologic effects of this drug on the conduction system have been variable and this variability has been attributed to the degree of vagal tone. The findings in this age group are similar to adults with simultaneous cholinergic blockade. This might be due to the direct depressant effects of disopyramide on the atrial and AV nodal tissue, and point to the potential usefulness of this drug in the pediatric age group.

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We measured the digoxin concentration in both plasma and erythrocytes in 75 patients by radioimmunoassay during digoxin maintenance therapy. Mean plasma digoxin concentration was 0.90ng/ml and mean erythrocyte digoxin concentration was 1.44ng/ml in 75 patients. The ratio of digoxin concentration of erythrocyte to plasma during maintenance therapy was 2.24 in all patients, 1.63 in patients with therapeutic plasma digoxin levels, and 3.52 in patients with subtherapeutic plasma levels. There was a significant correlation between erythrocyte and plasma digoxin concentrations in therapeutic plasma levels (r=0.53, p<0.001).
Patients on maintenance digoxin therapy were classified into 6 groups according to plasma and erythrocyte digoxin concentrations; in group I, 7 patients with both low plasma and erythrocyte digoxin concentrations, were poorly controlled in respect to heart failure; in group II, 19 patients with low plasma and medium erythrocyte digoxin concentrations failed to show compliance; in group III also, 3 patients with therapeutic plasma and low erythrocyte digoxin levels showed poor compliance; in group IV, 41 patients with both medium plasma and erythrocyte digoxin levels, were well controlled in respect to heart failure and all were compliant. Careful observation was required to avoid digoxin intoxication in group V with therapeutic plasma and high erythrocyte digoxin concentrations, and in group VI with high plasma and high erythrocyte digoxin concentrations.

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Serum haptoglobin (Hp) was estimated in 76 cases of ischemic heart diseases (IHD) and 151 healthy individuals. A statistically significant rise in Hp level was observed in IHD cases. The rise was independent on the age and blood type of the cases but was more predominent in males as compared to females.
The increase in Hp level was noticed after the third day of coronary attack and peak level was obtained between the 7th to 9th day. Hp level was closely related to the degree of myocardial damage. No rise was seen in cases of angina whereas maximum rise was noticed in patients with multiple infarcts.
Hp phenotype pattern in IHD cases was not different from that of control cases.

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Two different conditions responsible for cardiac hypertrophy in the rat were investigated: the first one is isoproterenol-induced myocardial infarct, the second is exposure to hypoxia (0.42 atmospheres/24h) in hypobaric chamber. To demonstrate that in both experimental models stimulation of protein synthesis is an absolute requirement to induce cardiac hypertrophy, a variety of techniques were employed including: evaluation of dry heart weight value, concentration of radiothallium (²⁰¹Tl) in the heart and effects of inhibitors of protein synthesis (Puromycin). Experimental results have showed: (A) a significant increase (p<0.001 as compared to control group) of dry heart weight values both in isoproterenol-treated and hypoxic rats; (B) a significant increase over control group (p<0.001) in myocardial ²⁰¹Tl concentration in isoproterenoltreated rats; (C) total inhibition of cardiac hypertrophy in Puromycin treated group subjected to hypoxia.
Finally, on the basis of different mortality observed in infarcted (85.0%) or hypoxic (5.0%) rats treated with Puromycin (40mg/Kg body weight i.p.) a different role of cardiac hypertrophy in 2 experimental conditions is postulated: in the case of infarct-like lesions the cardiac hypertrophy has compensatory significance; under hypoxic stimulus is only due to increased cardiac work.

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Alterations of regional left ventricular myocardial function immediately after coronary artery branch ligation as related to the total left ventricular function were determined by utilizing left ventricular pressurewall thickness loop in 6 anesthetized open-chest dogs. End-diastolic wall thickness was decreased immediately from 11.54±0.50mm (standard error of the mean) of control to 10.99±0.50mm in 5 to 10min after ligation (p<0.05), while regional myocardial work calculated as the loop area, was also decreased from 27.5±6.1 to 19.3±5.8×10³dyn/cm (p<0.05), indicating that the local Frank-Starling curve at the myocardium was depressed during ischemia. At the site where the ligation did not have effect, end-diastolic wall thickness and the regional work did not change significantly. Analysis of the shape of the loop revealed that the myocardial shortening was incomplete during the systolic ejection phase, and that the myocardial relaxation occurred very early in the ventricular relaxation phase after ischemia without alterations in the isovolumic contraction phase. These findings are compatible with those reported on isolated cardiac muscle strips during anoxia. The left ventricular pressure-wall thickness loop is superior to the pressure-length loop in that the former can be applied easily for clinical purposes and that the former utilizes a more direct relationship of pressure to its generator than the latter. Thus, primary alterations of myocardial function during ischemia were clarified accurately by utilizing the present method in the left ventricle in situ.

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We determined the details of ventricular activation sequence during the onset of ventricular fibrillation in 6 dogs. Unipolar electrograms were simultaneously recorded from 192 ventricular epicardial sites evenly spaced in a 3 by 3cm square area surrounding 2 central sites to which stimuli for inducing fibrillation were delivered. In 5 dogs, 2 to 10msec duration pulses with amplitudes of 150 to 220v were used to induce fibrillation, and in 1 dog, 3 successive premature stimuli of 3v intensity were used to induce fibrillation. In 2 dogs the pattern of activation at the onset of fibrillation was compatible with local reentrant paths near the stimulus site. Fibrillation was induced with a single high intensity pulse in both of these dogs. In the other 4 dogs, the pattern of activation at the onset of fibrillation was highly suggestive of reentrant paths distant from the stimulating electrodes. In 3 of these dogs fibrillation was induced by a single high intensity pulse and in the other it was induced by 3 repetitive stimuli. Activation patterns resembling supraventricular activation occurred prior to fibrillation in the latter animal.
The data demonstrate 2 distinct modes of onset of electrically induced ventricular fibrillation. The findings support local reentry in the region of the stimulus site as the mode of onset of fibrillation in some animals and possible reentry at sites distant from the stimulus site with participation of the specialized conduction system in other animals. The differences in mode of onset of electrically induced fibrillation may be responsible for instability of fibrillation threshold measurements in some animals. In addition the role of the specialized conduction system in the onset of fibrillation may be responsible for the effects of sympathetic and vagal stimulation on fibrillation threshold.

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A case of double-orifice mitral valve (duplication of the mitral valve) in an 18-month-old baby is presented. The valve showed significant regurgitation and was replaced with a No.20 Lillehei-Kaster mitral prosthesis. Patient is kept on dipyridamole (Persantin) 10mg/Kg and aspirin 50mg/Kg daily to avoid postoperative thromboembolic complications.
It is emphasized that valve replacement should be the treatment of choice in severe mitral regurgitation associated with double-orifice mitral valve.

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It was demonstrated that the levels of brain CA were higher in SHR than NTR and that CA levels and turnover rates in SHR were changed during brain ischemia following BCL. Because of increase of DA in contrast to NA, brain ischemia in SHR may cause lowering activity of dopamine-β-hydroxylase rather than that of tyrosine hydroxylase. Futhermore, the fact that characteristic behaviors related to decreases of CA during ischemia, for example rolling, circling and jumping, occured after 3h of BCL and later in spite of increases of DA may probably reflect changes of DA receptors in SHR.
Those results may he summarized that there are some abnormalities of brain CA system, including receptors, in SHR.

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The common male SHRSP died of stroke in almost 100% and the female in 90% under specific pathogen-free system. However, the male SHRSP derived from non-stroke parents died of heart failure in 30-41%. The SHRSP died of possible heart failure, showed the increase of heart weight, cardiomegaly, particularly of left ventricle. The heart of SHRSP died of heart failure revealed yellow colour macroscopically and there fatty metamorphosis microscopically. The myocardium showed hypertrophy, fibrosis, fatty metamorphosis and disseminated infarction. The coronary artery in the myocardium showed moderate thickening of the media with occasional blood clot. The residual muscle cells in myocardium revealed atrophy, fragmentation and fatty metamorphosis.It may be concluded that the SHRSP derived from non-stroke parents shows possible heart failure in high frequency and reveales myocardial changes with fibrosis, infarction and fatty metamorphosis.

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A marked difference in ECG and VCG patterns of SHR and SHRSP from those of WKY was noted even at the prehypertensive stage, suggesting that this might be of hereditary alteration and possibly an index of the genetic predisposition of hypertension. However, since SHR patterns increase with aging, further study is needed to exclude the secondry effect of hypertension.

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On the basis of the obtained results an essential difference in the responsiveness to L-dopa between SHRSP and SHRSR is postulated. Such a specific difference in responsiveness to L-dopa might be useful to analyze the pathophysiological alteration of blood brain barrier (BBB) leading to stroke, and also have clinical implication for detecting the alteration of BBB which appears to be of predictive value of stroke. Furthermore, since the reduction of rCBF was proven to be a causative factor of cerebrovascular lesions in SHRSP, the improvement of rCBF by L-dopa, especially by its combination with decarboxylase inhibitor, which is being clinically applied for the treatment of Parkinson's disease, might be useful for preventing stroke in man. The present study confirmed the theoretical basis for the effectiveness of these chronic treatments for preventing stroke in SHRSP which had been reported by Yamori and Horie (JAP CIRCIL J 39: 616, 1975).

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In the present study, it became clear that β-blocker (propranorol) had effectively improved rCBF in adult SHRSP with sever hypertension in which rCBF was significantly lower than control WKY. Yamori and Horie's previous studies clarified the BP reduction in SHRSP with severe hypertension increased rCBF and prevented the development of cerebrovascular lesions (STROKE 8: 456, 1977). It is noteworthy that β-blocker, without reducing BP significantly in SHRSP with severe hypertension, increases rCBF significantly. Because of the high frequency of pulse rate over 400/min in conscious rats, blood flow in cerebral arteries near recurrent branchings is regarded as being nearly similar to steady flow. Since our previous hemorheological study demonstrated that pulsatile flow increased flow into recurrent branches and that the effect of pulsation was augmented with the increased pulse pressure (Niimi et al: JAP HEART J 20: 681, 1979), it is theoretically considered that β-blocker, which reduces heart rate without affecting BP and thereby increases pulse pressure, favourably increases the reduced blood flow into recurrent arteries especially under severe hypertension. The present experiment substantiated this hypothesis and suggested that β-blocker, even without reducing blood pressure markedly, would be useful for preventing cerebrovascular lesions caused by hypoxia due to reduced rCBF in the predilection sites of stroke fed by recurrent arteries.

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We compared the hypotensive effects of the water extracts of a number of Basidiomycetes drugs, and found that the extract of Fomes pinicola caused marked decrease of blood pressure of SHR and SHRSP when administrated intraveneously. Therefore, we purified the effective substance in the extract of Fomes pinicola by sequential fractionation on columns of DEAE cellulose and Sephadex G-75, and obtained an electrophoretically homogeneous fraction. Component analysis suggested that this substance is either a glycopeptide or a glycoprotein containing large proportions of galactose, mannose, and fucose.

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We compared the hypotensive effects of fractions with molecular weights of 500 to 1, 000 obtained from hot water extracts from twelve kinds of citrus peel. Intravenous administration of fractions from mandarine orange, lemon, grapefruit, yuzu, orange, iyokan, narutokan and sudachi showed marked falls of blood pressure in SHR and SHRSP. Furthermore, we fractionated the fraction from lemon peel by HPLC, and isolated a compound which is considered to be a fravonoid.

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We attempted isolation of the hypotensive substance contained in hot water extracts of chlorella raw cells. When chlorella extracts were fractionated by gel filtration, fraction E showed a depressive effect. Blood pressure of SHR and SHRSP showed falls of about 60mmHg at 1 hour after intravenous administration and of 30 to 40mmHg at 2 hours after intragastric administration. Fraction E was subsequently purified by passage through a column of Sephadex G-10, and then crystallized from ethanol. Both the crystalline compound and the mother liquor showed hypotensive effects, but the effect of the latter was more potent. The crystalline compound was identified as adenosine by means of chemical and physical methods, and the mother liquor was considered to be a mixture of adenosine and an unknown compound containing glycine. As a result, the hypotensive effect of fraction E on SHR and SHRSP may be ascribable to adenosine or to an oligopeptide with a molecular weight of approximately 200.

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Various kinds of experimental diets were administered to male SHRSP and their effects were examined. Although the experiment is under observation, the following results were obtained. In the casein or fish meal diet groups, whether in 12% or 24% crude protein, strokes were prevented. Meanwhile, in the fish meal diet groups with soybean cake or gluten, which contained 15-22% crude protein, gain in body weight, the level of blood pressure and the incidence of strokes seemed to be approximately the same degree as the control.

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Although it can be seen from above observations that (1) in male SHRSP, there were increasing activities of AT III with age reaching a peak on the age of high incidence of stroke, and (2) in female SHRSP, those of AT III were significantly higher compared with those of female WKY aged 3 to 9 months old,
there were no marked difference in levels between male SHRSP and WKY. This leads us to conclude that there may be a certain correlation between higher values of AT III activity and the occurrence of stroke in its developmental course, but this high level of AT III may not be one of major factors for the stroke.
In addition, in female both SHRSP and WKY, higher levels of AT III would be due to the chronic effect of estrogen.

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There was a closer relationship between the heart weight and the liver weight than between the heart weight and the brain weight in old SHRSP. However, in SHRSP heart weight to liver weight ratios were still greater than those in WK, indicating the cardiac hypertrophy is a more dominant characteristics in hypertensive state. Hypertrophied hearts of more than 2.2g in weight, all with cerebral stroke, corresponded also to the heaviest group of the liver in old SHRSP. Pathological examinations of the liver showed that the characteristic pathological finding in old SHRSP was the fibrous thickning of the wall of central vein ("central sclerosis") and a tendency toward fibrosis of the liver. Laboratory tests of 'very old' SHRSP showed increase in (a)BUN, (b)GOT and LDH and (c)GPT, which corresponded to (a)hypertensive renal vascular lesions (arterionecrosis, glomerular fibrosis and arteriosclerosis), (b)myocardial lesions (infarction and extensive perivascular fibrosis) and (s)liver damage due to congestion.
These experimental studies indicate that cardiac hypertrophy in old SHR is closely related with the congestion of the liver which is also hemodynamically over-loaded in long-standing hypertensive state.

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The thymuses of young SHR rats before developing hypertension had reduced numbers of immature T-lymphocytes which were detected by the rosette formation test with guinea pig erythrocytes, whereas the thymuses of other eight rat strains tested contained about 60% rosetting cells. The number of rosetting cells progressively decreased with age. The blastogenic responses to PHA of the SHR rat lymphocytes was depressed to less than one fifth when compared to those of other rat strains including W/Mk rats, the original colony of the SHR rats. Other cell-mediated immune responses, including delayed hypersensitivity, allograft rejections, and a cooperation of T- and B-lymphocytes to produce humoral antibody formation were significantly depressed when compared to those of other rat strains.

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