The purpose of this study was to clarify the factors influencing the clinical course and prognosis in variant angina. Also, the mechanism of acute myocardial infarction in variant angina is reviewed. The subjects were 110 patients with variant angina who, after the initial visit or admission, were observed for a period of at least 2 months, the average observation period being 68±49 months (range: 2 months-16 years). The incidence of acute myocardial infarction was 21.8% of these patients and 87.5% of the infarctions occurred within 1 month of the initial visit or admission. In variant angina, the average rate over 1 year was 2.2%; however, in classical angina the rate was 3.7% and in postinfarction angina 5.0%. The mortality rate was 5.5%, with death in the majority of cases occurring within 1 month, as in myocardial infarction. When treatment was stopped, spontaneous remission occurred in at least 26 of the 110 cases (23.6%). Beyond 3 months, the remission continued in 19 of these 26 cases. Seven cases had acute myocardial infarction in spite of the suppression of anginal attacks with administration of calcium antagonists. Apparently coronary spasm is the cause of anginal attacks, and the cause of acute myocardial infarction in patients with variant angina appears to be coronary thrombus formation.

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In a series of 1, 000 consecutive autopsy cases, we evaluated the clinical utility of thallium-201 (T1-201) myocardial scintigraphy and electrocardiography (ECG) in 101 patients who had been studied while alive. Fifty-five cases had myocardial infarctions (MI) at autopsy. The T1-201 scintigram and ECG in diagnosis of MI showed sensitivities of 68% and 60%, specificities of 87% and 83%, and diagnostic accuracies of 76% and 70%, respectively. The sensitivity of the T1-201 scintigram was 70% in anterior MI, 80% in postero-inferior MI, 25% in lateral and subendocardial infarction. The sensitivity was 88% for large massive MI, but was low in scattered (50%) or middle-sized MI (17%). The diagnostic limit of the resolution of T1-201 scintigrams was 4.5cm in long diameter. All 8 cases with MI of less than 4cm could not be diagnosed with the technique. There were 48 cases of large MI (more than 5cm), but 8 cases could not be diagnosed by scintigraphy because of non-transmural or scattered MI. A comparison of the T1-201 scintigram and ECG showed that 27 cases out of 60 cases were diagnosed by both methods, 14 only by the T1-201 scintigram, 9 only by ECG and 10 by neither method.

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Ambulatory electrocardiographic monitoring was performed in 18 children with a congenital complete heart block (CCHB). They had no cardiac structural anomalies. These patients could be divided into 3 groups according to the pattern of fluctuations in beat-to-beat ventricular rates. Type 1 patients showed rapid and transient fluctuations and demonstrated a high correlation between atrial and ventricular rates. Type 3 patients showed a constant ventricular rate and little variation through the 24 hour period and there was no appreciable correlation between atrial and ventricular rates. Twelve of 18 patients had additional arrhythmias. A few sporadic ventricular premature contractions (VPCs) were found in 9 patients, and bigeminy of VPCs or ventricular tachycardias were seen in 2 patients during exercise. Frequent and sudden prolongation of RR intervals was found during sleep in 3 patients. The longest intervals of ventricular asystoles were 7.2, 3.2 and 3.2sec, respectively. The mechanism of this phenomenon appeared to be not only an exit block, but also arrest or a lack of automaticity of a subsidiary pacemaker. One of these patients developed frequent Stokes-Adams attacks. Type 3 patients with sudden prolongation of RR intervals and/or frequent ventricular arrhythmias should be under careful observation. Ambulatory electrocardiographic monitoring is recommended for children with CCHB for evaluation of potential risk factors for Stokes-Adams attacks.

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Electron microscopic cytochemical studies of the basement membranes of myocardial cells and capillaries were performed in 13 patients with tetralogy of Fallot who were divided into 2 groups. Group 1 included 7 patients in the early stage of the disease, ranging in age from 7 months to 5 years. Group 2 consisted of 6 patients in the far advanced stage of the disease, ranging in age from 30 to 46 years. The operatively excised infundibular muscles of the right ventricle were prepared for conventional electron microscopy and electron microscopic cytochemistry. The anionic sites in the basement membranes were characterized by cationic polyethyleneimine.
The basement membrane ultrastructures of the myocardial cells and capillaries in the early stage of tetralogy of Fallot showed no apparent alterations with regular distribution of anionic sites, particularly in the external lamina of the basement membranes. In contrast, irregular thickening, wide splitting and lamination of the basement membranes of myocardial cells and capillaries, always associated with derangement and focal loss of anionic sites in the membranes were consistently observed in the far advanced stage of tetralogy of Fallot.
The aforementioned results suggest that altered surface membrane integrity of myocardial cells and capillaries resulting from pathologic changes of the basement membranes are an important pathogenetic mechanism responsible for progressive degeneration of infundibular muscle cells and myocardial dysfunction in the course of tetralogy of Fallot.

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The pathophysiology of left ventricular hypertrophy (LVH) in hypertensive patients is still an intriguing point. The lack of a close relationship between LVH and systolic or diastolic blood pressure at rest, previously observed by other investigators, was confirmed in our group of 45 patients with uncomplicated primary hypertension. The strength of correlation between echocardiographic left ventricular mass (LV Me) and blood pressure, expressed as incremental area (IA=total area under the curve-basal area), however, increased during bicycle exercise testing (r=0.33, p<0.05 for diastolic blood pressure; r=0.39, p<0.01 for systolic blood pressure; r=0.41, p<0.01 for mean arterial pressure). Other echocardiographic parameters of myocardial mass such as LVM index (LVMI) and septal thickness (ST) were also significantly correlated with blood pressure during exercise.
These results suggest either that blood pressure during exercise is a better index of the cardiac workload than resting blood pressure or that the pathogenesis of cardiac hypertrophy involves an enhanced reactivity to adrenergic drive, particularly stimulated during ergometric exercise.
Increased blood pressure alone, however, only partly accounts (about 20%) for the increase in myocardial mass in hypertensive patients; other factors, therefore, need to be further investigated for a better understanding of the pathophysiology of left ventricular hypertrophy.

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The validity of the captopril test for primary aldosteronism (PA) was tested in patients with surgically verified PA (n=12) or essential hypertension (EHT, n=20) with different levels of sodium intakes. The patients were scheduled on 7 days each of three regimes of the prepared diet containing 34, 120 and 340mEq of sodium chloride per day, and the captopril test was repeated in each period. For the test, captopril (50mg) was administered orally at 9:00A.M. after 1 hour of rest in a supine position, and venous blood samples were obtained before and 90min after drug administration. Plasma aldosterone concentration (PAC; ng/dl) and plasma renin activity (PRA; ng/ml/h) were measured by radioimmunoassay. Under the three different sodium intakes, a PAC/PRA ratio greater than 20 at 90min after captopril administration was sufficiently sensitive (0.95, 19/20) and specific (0.92, 55/60) to identify PA. Similarly, PA was associated with a PAC above 15ng/dl 90min after captopril. There were no complaints associated with the antihypertensive effects of the drug even when patients were sodium-restricted. These results confirmed that the captopril test is safe and useful for screening out-patients for PA, independent of individual differences in sodium intake.

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Acute hemodynamic changes induced by two beta-blocking agents, bunitrolol and propranolol, in patients with ischemic heart disease were studied.
Besides possessing negative chronotropic and inotropic effects which were demonstrated by decreased heart rate (HR), cardiac index (CI) and double product (DP) of the heart, propranolol significantly increased systemic vascular resistance (SVR, 12%, p<0.05) and the time constant of left ventricular (LV) isovolumic pressure fall (T, 10%, p<0.01). With bunitrolol, no significant changes were observed in indexes reflecting chronotropic and inotropic states of the heart, and CI and DP were essentially unchanged. Only LV systolic pressure (-5%, p<0.01), LV enddiastolic pressure (EDP, -17%, p<0.01) and T (-10%, p<0.05) decreased significantly. Systemic vascular resistance (SVR) decreased, though insignificantly.
Myocardial oxygen supply-demand balance in the resting state was not improved by propranolol as evidenced by the fact that CI decreased in proportion to the decline in DP. In contrast, ischemia at rest was apparently improved by bunitrolol because LV wall stress decreased due to the reduction in LV volume which was suggested by the decline in LV systolic pressure and LVEDP while CI remained constant. Improvement of the time constant T might be strong evidence of relief from ischemia.
Bunitrolol might be effective even in patients with overt heartfailure, especially that due to ischemic heart disease because of its lack of negative inotropic action and its ameliorating effect on ischemia at rest.

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Twenty-four hypertensive patients were divided into a group A with negative U waves (n=8, mean age, 50±11 years) and a group B without negative U waves (n=16, mean age, 49±11 years). Echocardiographic findings were compared with a group of 20 age-matched normotensive subjects without cardiovascular disease (mean age, 49±11 years). In addition, the effects of the antihypertensive agent tripamide were assessed in groups A and B. Although hemodynamic parameters such as left ventricular end-systolic and diastolic dimensions, stroke volume and cardiac output were elevated in group A, group B showed an increase in total peripheral resistance. Thus, group A was characterized by high cardiac output, while group B displayed increased peripheral resistance. Tripamide was administered to 14 patients. In group A (6 patients receiving tripamide), left ventricular end-systolic and end-diastolic dimensions were significantly reduced by tripamide along with stroke volume and cardiac output. However, in group B the only significant change in hemodynamic parameters after tripamide administration was a drop in total peripheral resistance. These findings suggest that both the hemodynamics of hypertensive patients and responses to tripamide vary with the presence of negative U waves.

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To investigate mechanisms for a reduced coronary vasodilatory capacity in patients with hypertrophic cardiomyopathy (HCM), maximum coronary blood flow and minimum coronary vascular resistance were measured by administering dipyridamole (0.56mg/kg) to 19 patients with non-obstructive HCM and to 7 control subjects. The maximum coronary blood flow was significantly lower (131±46 vs 192±41ml/100g•min, p<0.01, mean±SD) and the minimum coronary vascular resistance was significantly higher (0.64±0.23 vs 0.44±0.13mmHg/ml/100g•min, p<0.05) in HCM patients. There were no significant correlations between maximum coronary blood flow or minimum coronary vascular resistance and the baseline left ventricular end-diastolic pressure or the severity of systolic narrowing of the left anterior descending artery of the septal perforator. In contrast, the minimum coronary vascular resistance was correlated significantly with the left ventricular muscle mass (r=0.55, p<0.05), but its correlation to small coronary vessel disease could not be studied. In addition, HCM patients with a reduced exercise tolerance (<7 metabolic units) demonstrated a significantly lower maximum coronary blood flow and higher minimum coronary vascular resistance than control subjects.
These findings suggest that: (1) there is a group of HCM patients who have a reduced coronary vasodilatory capacity, (2) abnormal coronary vasculature is a possible underlining mechanism of HCM, either due to inadequate growth unassociated with left ventricular hypertrophy or as small coronary vessel disease, and (3) a reduced coronary vasodilatory capacity.

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In order to investigate the effect of a rise in aortic pressure on coronary flow reserve and also on the difference of its effect according to the methods used to raise aortic pressure, this experiment was performed.
Using 7 anesthetized dogs with heart rate held constant by a pacemaker, both the resting and the peak reactive hyperemic left circumflex coronary flow were measured following raising of the aortic pressure by either descending thoracic aorta constriction or methoxamine injection.
The resting and peak reactive hyperemic coronary flows both increased linearly following the rise in aortic pressure. The magnitude of the resting flow increment and the resting coronary vascular resistance following raising aortic pressure did not differ significantly between the two different methods. However, the magnitude of the peak hyperemic flow increment and the peak hyperemic coronary vascular resistance following raising aortic pressure were significantly smaller with methoxamine injection than with aortic constriction.
These data indicate that coronary flow reserve increases proportionally with a rise in aortic pressure. However, the magnitude of the increment of coronary flow reserve is smaller following an alpha-adrenoceptor-mediated rise in aortic pressure, because the maximal coronary vasodilation was reduced by alpha-stimulated coronary vasoconstriction.

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The neurohormonal contribution to high blood pressure was investigated in 9 conscious two-kidney, two-clip Goldblatt (2K2C) hypertensive dogs during evolution of the benign and malignant phases after application of bilateral renal clips (BRC). Serial measurements were taken of the plasma renin activity (PRA), plasma angiotensin I-immunoreactivity (Ang I-ir), plasma angiotensin II-ir (Ang II-ir), renin substrate (RS) catecholamines [epinephrine (Epi) and norepinephrine (NE)] and vasopressin (AVP). Immediately after BRC, the elevation of the blood pressure (86±3 to 110±3mmHg, p<0.01) was associated with an increase in heart rate (93±3 to 114±9 beats/min, p<0.01). These hemodynamic changes were accompanied by increases in PRA, Ang I-ir, Ang II-ir, Epi, NE and AVP. The renin angiotensin system was activated throughout the 3 week period following BRC, as indicated by increases in PRA, Ang I-ir and Ang II-ir. Catecholamines were elevated immediately after BRC, followed by a return toward the control values. AVP underwent a slight but not significant elevation after BRC, which was sustained during the 3 weeks.
Production of malignant hypertension was affected by occlusion of one of the adjustable renal clips 3 weeks after BRC. A marked elevation of the blood pressure was associated with significant increases in PRA, Ang I-ir, Ang II-ir, Epi, NE and AVP, compared with the pre-occlusion values.
In addition, pharmacologic experiments were performed in 6 of 9 dogs. Administration of angiotensin I converting enzyme inhibitor (SQ 14225) reduced the blood pressure both in the benign and malignant phases of 2K2C renovascular hypertension, and a ganglionic blocking agent (hexamethonium) also decreased the blood pressure. However, a specific, vascular acting AVP antagonist failed to reduce the blood pressure significantly.
From this study, it seems likely that severe renal ischemia caused by renal clipping caused the activation of the renin-angiotensin and the sympathetic nervous system and elevation of serum vasopressin. However, there are no apparent differences between the benign and malignant phases of renovascular hypertension, except for the marked elevation of neurohormone levels in malignant hypertension.

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This study was designed to investigate the role of calmodulin in adrencrgic neurotransmission of resistance vessels. The effects of various calmodulin antagonists (trifluoperazine, W-7, calmidazolium, chlorpromazine, fluphenazine) on the vascular responsiveness and norepinephrine overflow from adrenergic nerve endings were examined in perfused rat mesenteric vasculature preparations. Pressor responses to electrical nerve stimulation or exogenous norepinephrine were inhibited dose-dependently by each calmodulin antagonist. Norepinephrine overflow from the sympathetic nerve endings during electrical nerve stimulation was also suppressed by calmodulin antagonists. These results indicate that calmodulin antagonists affected both pre- and post-synaptic sites of adrenergic neurotransmission, suggesting that calmodulin is involved both in neurosecretion and vascular smooth muscle contractions in peripheral resistance vessels.

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The effects of the calcium antagonist, nicardipine, on blood pressure and renal hemodynamics were examined in rabbits with norepinephrine- and angiotensin II-induced elevation of blood pressure. With norepinephrine-infusion, the mean arterial pressure increased from 84±4 to 118±4mmHg accompanied by decreases in heart rate (10%) and renal blood flow (45%). In contrast to the changes in renal blood flow with norepinephrine-infusion, renal blood flow following angiotensin II-induced elevation of blood pressure was decreased by more than 60% at the same degree of elevation of mean arterial pressure. Both intravenous and intrarenal administration of nicardipine (1μg/kg) reduced the mean arterial pressure and restored the decreased heart rate and renal blood flow in both norepinephrine- and angiotensin II-infused animals. Intrarenal injection of nicardipine decreased the elevated mean arterial pressure of angiotensin II-induced hypertension more than did intravenous injection (16±2 vs. 11±3mmHg, p<0.05). Renal nerve denervation did not lead to any significant effects on the mean arterial pressure, heart rate and renal blood flow following intravenous or intrarenal injection of nicardipine in norepinephrine-infused animals. On the other hand, in angiotensin II-induced elevation of blood pressure, the potentiated hypotensive effect of intrarenal injection of nicardipine was lost in renally denervated animals.
In conclusion, the calcium antagonist, nicardipine, was shown to reduce the acutely elevated blood pressure caused by norepinephrine or angiotensin II. In angiotensin II-induced elevation of blood pressure, the renal vasculature may play a more important role in both pressor and depressor aspects in the regulation of blood pressure as compared to its role in norepinephrine-induced hypertension.

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A 20-year-old woman whose echocardiograms showed a rare evolution from hypertrophic cardiomyopathy (initially with obstruction and 4 years later without obstruction) to dilated cardiomyopathy over an 8-year observation period is described.

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A 45-year-old female without coronary risk factors showed a 20kg decrease in body weight, hyperhydrosis, palpitations and dyspnea on exertion for 2 months, and nocturnal dyspnea for 1 month before admission. She did not notice chest pain indicative myocardial infarction or fever suggestive myocarditis. Graves' disease was confirmed by exophthalmos and elevated titers of T₃ and T₄ thyroid hormones. Cardiac catheterization studies demonstrated no significant coronary artery disease but showed akinesis of the anteroseptal and apical walls which suggested myocardial infarction.
Thyroid hormone may directly influence myocardial oxygen supply and demand and, by some unknown mechanism, cause a critical imbalance in coronary circulation resulting in myocardial infarction.

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Premature atherosclerosis with a particular predilection to the coronary arteries is a well-known complication of homozygous familial hypercholesterolemia. However, well documented involvement of the aortic root and valve with aortic stenosis has not been recognized frequently antemortem. Clinical, echocardiographic, hemodynamic and angiographic features of a case with valvular and supravalvular aortic stenosis secondary to homozygous familial hypercholesterolemia are described. Surgical relief of the left ventricular outflow obstruction was not attempted because of the patient's refusal.

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