Some 227 patients who showed a 50% or greater narrowing of at least one major coronary artery in the first study underwent recatheterization at a mean interval of 35.6 months. Coronary arterial lesions and the degree of narrowing [i.e., normal (absent), 25%, 50%, 75%, 90%, 99% and complete occlusion (100%)] were classified in accordance with the AHA reporting system. When the lesions in the second study showed a change of equal or more than 2 in the above 7 stages in comparison with the first study, either progression or regression was determined. Of the 227 patients, progression occurred in 73 (32%) and regression was found in 7 (3%). In the aggravated group in symptom, progression was noted in 58%, and even in the stabilized group, progression was observed in 22%. As a result of the second study, 15 (21%) out of 73 patients showing progression underwent surgical treatment, and more than half of these cases (9/15) were constituted by the stabilized group. During the above following-up periods, myocardial infarction occurred subsequently in 14 (19%) out of 73 patients showing progression. Up to the present time, sudden deaths occurred in 8 patients, and 5 out of 8 patients were also of the stabilized group. The authors wish to emphasize from these findings the necessity of aggressively pursuing restudy even in stabilized cases showing symptoms of ischemic disease.

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The relationship of continuous ambulatory intra-arterial blood pressure over a 24-hour period and awake resting hemodynamic parameters measured by echocardiography was studied in 21 patients with essential hypertension (WHO stage I II) 1) Left ventricular wall thickness at end-diastole correlated strongly with average SBP and weakly with average DBP during both waking and sleeping periods. 2) Variability of blood pressure taken during waking and sleeping periods was not significantly correlated with any hemodynamic parameters measured by echocardiography. 3) Variability of SBP during sleep had a significant correlation with age; however the fall of blood pressure during sleep had no significant correlation with age. 4) Fall of blood pressure during sleep was significantly correlated to resting awake TPR. In patients with essential hypertension, the above results demonstrate that subjects with thicker left ventricular wall have higher average continuous blood pressure over 24-hours and suggest that there is a tendency for greater falls in blood pressure during sleep to occur in subjects with higher TPR and that older subjects have greater variabilities of SBP during sleep.

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The feasibility of using overnight urine as an alternative to 24-hr urine was examined on measures of dietary intake of sodium (Na), potassium (K) and protein as well as the sulfur amino acids, which are contained mainly in animal protein. It was also of interest whether urinary excretions of taurine (Tau : final metabolite of sulfur amino acids, contained mainly in animal protein) and excretions of 3-methylhistidine (3-MHis : the product of breakdown of skeletal muscle protein, quantitatively excreted into urine) were appropriate in assessing the dietary intake of animal protein and total protein, respectively. Overnight urine specimens were collected from 16 subjects (19 to 60 years old) with normotension or borderline hypertension without complications. Creatinine (Cr) ratios to Na, K, urea nitrogen (UN) and inorganic sulfate (SO₄) derived from overnight urine and from 24-hr urine specimens showed significant correlations . Similar correlations were also found for the Na/K and SO₄/UN rations between overnight and 24-hr urine specimens. Concentrations of Tau and 3-MHis ( mmol per g Cr) of overnight urine specimens were strong correlated with 24-hr urinary excretions of Tau and 3-MHis (μmol per day), respectively. Furthermore, significant correlations were found between 24-hr urinary excretions of UN and 3-MHis and between those of SO₄ and Tau. These results indicate that an overnight urine specimens are available for assessing dietary intakes of Na and K, as well as protein and sulfur amino acids in field studies.

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To determine whether abnormal Q wave in lead I or aVL may be of use to estimate the size of an extensive anterior myocardial infarction, electrocardiographic and left ventriculographic findings were analyzed in 45 patients with old extensive anterior infarction. All 45 patients had a significant narrowing in the proximal segment of left anterior descending coronary artery (LAD) and severe asynergy in anterolateral segment. The patients were divided into two groups ; Group II of 10 cases with remarkable extension of the anterolateral infarction into the inferoapical segment due to occlusion of very long LAD supplying the anterior half of posterior inter-ventricular groove. There were no statistical differences in the extent of anterolateral asynergy, number of abnormal Q waves in precordial leads and left ventricular ejection fraction between the two groups. While abnormal Q wave in lead I or aVL was present in 28 cases (80%) of Group I, it was observed in only 3 cases (30%) of Group II (p < 0.01). Thus, we can't rule out extensive anterior myocardial infarction even if abnormal Q waves are absent in lead I or aVL, in which abnormal Q waves may be cancelled by loss of electromotive force of inferoapical segment due to extension of the anterior infarction over the apex in cases with extraordinarily long LAD.

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The difference between normotensive rats (WKY) and spontaneously hypertensive rats (SHR) in functional and metabolic responses to ischemia was studied. Systolic arterial blood pressure of SHR (171.2 ± 2.9 mmHg) was significantly higher than that of WKY (135.3 ± 1.2 mmHg), and the left ventricular mass of SHR was larger than that of WKY. Hearts isolated from either WKY or SHR were perfused by the working heart technique. Ischemia was induced by lowering the afterload pressure of the working heart. Ischemia produced cardiac arrest, and decreased the tissue levels of adenosine triphosphate and creatine phosphate in both WKY and SHR. Recovery of mechanical function of the heart during reperfusion following ischemia in SHR was better than that in WKY, while recovery of the high-energy phosphates level in SHR was less prominent than in WKY. It is postulated that hypertension has a deleterious effect on myocardial energy metabolism in ischemic heart, even when cardiac mechanical function is maintained.

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An autopsied patient who showed typical dilated cardiomyopathy (DCM)-like features and was pathologically diagnosed with hypertrophic cardiomyopathy (HCM) is presented. The patient, a 60-year-old male at the time of death, died of intractable congestive heart failure. At autopsy the heart weighted 570g and showed marked left ventricular (LV) dilatation with a thin wall (ventricular septum/free wall of the LV=7mm/8mm). There was no evidence of significant stenosis in the extramural coronary arteries. Massive fibrosis was found in the middle and outer thirds of the ventricular septum and anterior wall of the LV (48% in the ventricular septum and 9% in the free wall of the LV). As myocytes were not present in the area with massive fibrosis, percent area of disarray was calculated excluding the area of massive fibrosis and found to be 30% in the ventricular septum. Based on the marked increase in the percent area of disarray, this case was diagnosed as HCM. The patient's 37-year-old son showed asymmetric septal hypertrophy on echocardiography (ventricular septum/posterior wall of the LV = 15mm / 11mm), marked LV hypertrophy on electrocardiography, and diffuse and marked disarray by endomyocardial biopsy. There were also LV dilatation (LV diastolic dimension =51 mm) and hypokinesis of the LV ; as a result, a diagnosis of HCM with features of DCM was made.

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Clinical studies were carried out during digoxin maintenance therapy to clarify three questions concerning digitalis therapy : optimal time for blood sample collection for serum digoxin concentration (SDC), the overlapping range of SDC levels in which some patients may be intoxicated while others are not, and both resistance and sensitivity of atrial fibrillation (AF) to digitalis. The SDC curve after a single dose of digoxin or β-methyldigoxin shows the appropriate sampling time to be at least 12 hours after the administration. The optimal time is 24 hours. The overlapping SDC range was 1.7-2.7 ng/ml. There were significant differences in CTR and ventricular rates in AF between intoxicated and non-intoxicated groups. This suggests that susceptibility to digitalis increases with the severity of underlying heart disease. Precipitating factors such as CTR should be taken into consideration, if the SDC is in the overlapping level. Digitalis resistance occurs in 6.7% of 105 patients with AF, and more frequently in hypertensive heart disease than others. Digitalis sensitivity occurs more often in the elderly and in patients with dilated cardiomyopathy. But it is not necessary to attain higher therapeutic levels for AF than for sinus rhythm. Clearly optimal digitalis therapy for AF can be best accomplished when precise clinical findings, SDC and EKG recordings are carefully monitored and used to correct treatment.

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Effects of a new selective β1 partial agonist, ICI 118, 587, on cardiac function were assessed in clinical settings. In 7 patients, responses to multistage treadmill exercise were studied before and after an acute intravenous injection of the drug. The heart rate and blood pressure were not altered by ICI 118, 587 at rest but increases in both parameters in response to exercise were significantly reduced. Neither oxygen consumption nor plasma norepinephrine level was modified by the drug both at rest and during exercise. The long term effects of ICI 118, 587 were assessed in 6 patients with mild to moderate cardiac failure consequent upon ischemic heart disease. After chronic administration of the drug exercise duration was increased. The symptom-limited maximal oxygen consumption increased by 16%, associated with prolongation of the exercise tolerance. In those patients who also had symptoms of angina pectoris, exercise levels which caused angina during the control study were tolerated without symptoms after ICI 118, 587. Twelve patients with nocturnal bradycardia resulting from atrial fibrillation or sick sinus syndrome were treated with ICI 118, 587. Monitoring of heart rate by 24-hour Holter ECG showed that ICI 118, 587 increased minimal heart rate during sleep. Being a β1-adrenoceptor partial agonist, it has both agonist and antagonist properties. Thus, ICI 118, 587 buffers the heart from an excessively low sympathetic tone which may occur during sleep and from an excessively high tone during exercise. It appears to be of benefit in the treatment of mild to moderate cardiac failure consequent upon ischemic heart disease. It also improves oxygen demand-supply imbalance without inducing further myocardial depression of inappropriate bradycardia at rest. ICI 118, 587 may therefore be described as a cardiostabilizer.

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A new inotropic agent, denopamine (TA-064) was shown to have a strong positive inotropic effect. Its effect on cardiac hemodynamics and metabolism was evaluated by using wall stress and direct measurement of myocardial oxygen consumption. With plasma concentration of denopamine (21-29 ng/ml on average), attainable by one single oral dose (10 mg), the positive inotropic effect was evident by the significant increase in peak (+) dp/dt (+15% increase from control), and shortening velocity of the left ventricle (+39%), when heart rate or blood pressure was not altered significantly. End-diastolic stress and endsystolic stress of the left ventricle, defined as indices of preload and afterload, respectively, were reduced significantly. The reduction of preload (-51%) was the result of improved left ventricular filling, and the reduction of afterload (-23%) was due to the increased contractility. Neither coronary sinus blood flow nor aortocoronary AV O₂ defference was changed. Consequently, myocardial oxygen consumption remained unaltered. When the dose is chosen properly, denopamine is able to exert salutary effects in patients with severe heart failure.

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The hemodynamic effects of a newly developed inotropic agent, amrinone (AMN) were studied and compared with those of dopamine (DA) and dobutamine (DB) in forty patients with pump failure due to acute myocardial infarction. Hemodynamic measurements were taken using a Swan-Ganz thermodilution catheter before and 5, 10, 15, 30, 60, 90 and 120 minutes after intravenous injection of AMN (1-2 mg/kg) for 3 minutes in eight patients, and also before and during drip infusion (3-7 μg/kg/min) of DA in fifteen patients and DB in seventeen patients. AMN showed maximal increases in CI, SVI and SWI, and maximal lowering in CVP and SVR 5 minutes after intravenous injection, while maximal lowering in PCWP occurred 10 minutes after injection. These significant hemodynamic changes lasted for 60 minutes after injection. Comparing the maximal hemodynamic effects occurring 5 minutes after injection of AMN with those of DA and DB, it was found that AMN increased CI to almost the same degree as DA, and lowered CVP and PCWP much more compared to DB. These results suggest than AMN possesses a dominant vasodilating effect in addition to its inotropic effect, which would greatly benefit the treatment of refractory heart failure ; AMN are the characteristic cardiovascular hemodynamic effects of as if catecholamine and a vasodilator were combined.

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The effect of a new inotropic agent, OPC-8212 (2(1H)-quinolinone derivative), on myocardial oxygen consumption (MV^^·O₂) following intravenous administration (1 and 3 mg/kg/min) was studied in normal and ischemic failing hearts in open chest dogs. Ischemic failing heart was obtained by intracoronary injection of 15-μm microspheres and volume loading. OPC-8212 significantly increased LV mad dP/dt and decreased mean aortic pressure, whereas heart rate was not altered in both normal and failing hearts. Despite the remarkable positive inotropic effect, this agent did not increase MV^^·O₂ in the normal hearts and even decreased MV^^·O₂ in the ischemic failing hearts associated with a decrease in LV end-diastolic pressure and hence, LV chamber size. These results indicate that OPC-8212 does not increase myocardial oxygen demand, probably because the increase in MV^^·O₂ by positive inotropic effect is offset by a decrease in MV^^·O₂ due to a decrease in chamber size. Thus, OPC-8212 may be promising for the treatment of congestive heart failure with reduced coronary flow reserve.

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To assess the hemodynamic effects of digoxin (0.01 mg/kg) on congestive heart failure, we evaluated 19 patients with decreased contraction force of left ventricle (old myocardial infarction n=9, and dilated cardiomyopathy n=10, group 1) and 8 patients with mechanical impaired left ventricular filling (mitral stenosis n=8, group 2). In groups 1 and 2, heart rate and pulmonary capillary pressure significantly decreased (p < 0.05). In group 1. stroke volume increased, but not significantly. In group 2, stroke volume increased significantly (p < 0.05). There were no significant changes in blood pressure and systemic vascular resistance in either group. We divided group 1 into two groups (group 1A : cardiac index increased more than 15%, group 1B : cardiac index increased less than 15%). In group 1A, cardiac index and % fractional shortening before digoxin administration were lower than in group 1B (1.97 + 0.27 vs 2.80 + 0.481/min/m², p < 0.001, and 10.9 + 8.0 vs. 19.5 + 11.9%, p < 0.05, respectively). These data suggested that digoxin exerted a positive inotropic effect with decreased pulmonary capillary pressure, but cardiac index did not always increase in congestive heart failure.

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