Simultaneous hemodynamic and radiocardiographic measurements were performed on 10 patients with mitral stenosis and pulmonary congestion for evaluating the acute effects of dobutamine (DB, 5 μg/kg/min), isosorbide dinitrate (ISD, 10 mg sublingually) or a combination of the two. DB alone produced a significant increase of the cardiac index (CI) from 2.9 ±0.1 to 3.7 ± 0.2 L/min/m² (p <0.01), but a modest increase in pulmonary artery diastolic pressure (PADP) and in pulmonary blood volume by approximately 15%, respectively. ISD alone caused a decline in PADP from 26 ± 2 to 18 ± 1 mmHg (p < 0.001), in right heart volume from 300 ± 36 to 215 ±18 ml/m² (p < 0.05) and in left heart volume from 321 ± 28 to 248 ± 20 ml/m² (p<0.05), but no change in the CI. Combined administration of the two agents resulted in favorable alterations in both hemodynamic variables : PADP decreased from 26 ± 2 to 20 ±1 mmHg (p < 0.01) and the CI increased from 2.9 ± 0.1 to 3.3 ± 0.1 L/min/m² (p < 0.05). Thus, DB alone had a tendensy to aggravate pulmonary venous congestion in our patients, while ISD is effective in reducing the congestive manifestations of heart failure due to its venodilating effects but less beneficial in increasing the CI. The combined therapy of DB and ISD appears to be extremely effective in restoring an adequate cardiac output and in relieving the symptoms of pulmonary vascular congestion in the presence of mitral stenosis.

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Although some studies suggest the involvement of a complement activation in the development of acute myocardial infarction, there has been little convincing evidence of the change of the complement in patients suffering from myocardial infarction. In 11 patients with acute myocardial infarction the serial changes of the total hemolytic complement titer (CH50), C3, C4, total serum protein and C3 conversion were investigated up to 120 hours after its attack. The level of CH50 and C4 increased consistently in the acute phase of myocardial infarction, but C3 did not show any change and total serum protein declined after 96 hours. β₁ A globulin, the split product of C3, could not be detected in the blood stream. These results suggest that the infarcted or ischemic myocardium would activate complements, and C3 might be consumed continuously by the infarcted or ischemic myocardium. Such consumption of complements should stimulate the production of complement and would give rise of an increase in C4 and CH50. It is suggested that activated complement might play a significant role in the development of myocardial infarction.

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The molecular weight (MW) of active renin (AR) and inactive renin (IR) was investigated in individual plasma samples from 15 essential hypertensive and 5 normal subjects. The patients with essential hypertension were classified into 3 subgroups : low plasma renin activity (PRA), normal PRA and high PRA. The MW of AR and IR was estimated by Sephadex G-100 gel filtration. IR in the eluates was activated with trypsin. Plasma renin activity and renin activity in eluates were measured by radioimmunoassay of angiotensin I. At least 3 sizes of AR (MW : 48, 000, 53, 000 and 57, 000) and 2 sizes of IR (MW : 53, 000 and 57, 000) were discovered, and the MW of AR was less than or equal to the MW of IR. The larger AR was predominant in the low PRA group and the smaller one in the high PRA group. This was also true for IR. This relation was also observed in the 2 types (high renin and low renin) of pooled plasma. In high renin pooled plasma the MW of AR and IR was about 48, 000 and 54, 000, respectively, while both were about 56, 000 in low renin pooled plasma. It appears that the larger type of AR and IR remains in the circulation in the suppressed renin state, and that the smaller type of renins enters into the circulation when the secretion of renins is enhanced.

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To identify the risk factors of borderline hypertension in the development of established hypertension, the relationship between the changes in blood pressure over 10 years and the clinical features in the initial year was investigated in a Japanese urban population. The occurrence of cardiovascular complications in cases with borderline hypertension were also studied. The prevalence of borderline hypertension in the initial year was 18.2%. On the basis of the blood pressure changes over 10 years, these subjects could be classified into the following 5 groups : (I) those with developing established hypertension, 19.0% ; (II) those with fluctuating between hypertension and borderline hypertension, 27.4% ; (III) those with remaining with borderline hypertension, 19.6%; (IV) those with fluctuating between borderline hypertension and normotension, 22.9% ; (V) those with improving to normotension, 11.2%. The later development of established hypertension was found in only 2.4% of normotensives in the initial year. Obesity and glucose intolerance were more frequently observed in group I (38.2% and 29.4%, respectively) than in the other groups. Diastolic blood pressures in the initial year were significantly higher in groups I and II than in III, IV and V. As for the occurrence of cardiovascular complications during the observation period, electrocardiographic abnormalities and hypertensive and/or arteriosclerotic retinopathy were not infrequently observed even in borderline hypertensives. Therefore, in subjects with borderline hypertension, continuous medical management, including correction of obesity as well as glucose intolerance, is necessary to prevent the development of established hypertension and subsequent cardiovascular complications.

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Prostacyclin (PGI₂) is produced in the vessel wall and acts as a vasodilator hormone. Measurement of plasma 6-keto-PGF_1α is considered to be an index of PGI₂ production. In the present study the effects of aging on the plasma 6-keto-PGF_1α levels were studied in 64 normotensive and 48 essential hypertensive males. The subjects were divided into 3 groups, i.e., young (24-39 years), middle-aged (40-55 years) and elderly (over 56 years) groups. Plasma 6-keto-PGF_1α was measured by specific radioimmunoassay after silicic acid column chromatographic purification. The 6-keto-PGF_1α levels were lower in elderly normotensive males (10.3 ± 1.4 pg/ml, mean ± SE, n=12) than in normotensive young males (15.3± 2.3 n=30, p < 0.05). The plasma 6-keto-PGF_1α levels in hypertensive elderly males (10.6 ± 1.3 pg/ml, n=10) is lower than in hypertensive young males (19.8 ± 2.2, n=17, p<0.01). These results indicate that the plasma 6-keto-PGF_1α levels decreased with age in both normotensive and hypertensive groups. Thus, PGI₂ production may decrease with age.

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Thirteen beta-blocking agents with different pharmacological properties were administered orally to 161 outpatients with essential hypertension for 5 weeks to assess their hemodynamic effects. Cardioselective ones, such as atenolol, metoprolol and acebutolol, reduced mean blood pressure (MBP) and the cardiac index (CI) without any changes of the total peripheral resistance index (TPRI). In the total 44 patients treated with these drugs, a positive correlation (r=0.529, p < 0.005) was found between the decrease in MBP and that of TPRI, but the decrease in MBP did not correlate with that of CI. Effects of non-cardioselective ones were classified arbitrarily into the following 3 patterns : 1) reduction of CI of more than 0.50 L/min/m² and a slight increase of TPRI by more than 150 dyne·sec·cm^-5·m² (nadolol, propranolol, oxprenolol and penbutolol), 2)reduction TPRI by more than 150 dyne·sec·cm^-5·m² (pindolol, bunitrolol and labetalol) and 3) the intermediate hemodynamic responses between the two patterns described above (carteolol, bupranolol and bufetolol). In all these 3 groups, the decrease in MBP correlated with that of TPRI (O the first group, n=45, r=0.557, p < 0.005 ; the second, n=37, r=0.525, p < 0.005 ; the third, n=35, r=0.612, p<0.005), but did not correlate with the decrease of CI. These results suggest that the antihypertensive effects of beta-blocking agents mainly depend on the reduction of peripheral resistance, although their pharmacological properties are not uniform and their cardiodepressant effects are variable. Reduction of cardiac performance with these beta-blocking agents seemed to be a consequence of overall pharmacological actions including beta-receptor blockade, central effects and membrane stabilizing effects, and it may be antagonized by intrinsic sympathomimetic activity and the reduction in afterload for the heart. Vascular beta-receptor blocking action may play a part in decreasing the degree of reduction of the total peripheral resistance index, while their intrinsic sympathomimetic action on the vascular site may induce vasodilating effects.

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In 14 patients with the left-sided concealed Wolff-Parkinson-White syndrome, the effects of changing atrial pacing site on the echo zone were evaluated. In 12 patients, re-entrant tachycardia was induced by premature stimuli both in the coronary sinus (CS) and the high right atrium (HRA). In the remaining 2 patients, the tachycardia was induced by premature stimuli only in the CS. The lower limit of the echo zone was shifted to a longer coupling interval during CS pacing in 12 patients. The longer effective refractory period (ERP) of the CS was responsible for the shifting of the lower limit of the echo zone to a longer coupling interval. The upper limit of the echo zone was shifted to a longer coupling interval during CS pacing in 10 patients. The difference of atrial conduction times from the site of stimulation to the 2 conduction pathways ( the normal conduction pathway and the accessory pathway) is thought to be responsible for the shifting of the upper limit of the echo zone.

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A total of 135 patients with ventricular septal defect (VSD) under 15 years of age, without associated cardiac lesions, underwent surgical repair by 3 different approaches of trans-pulmonary arteriotomy (PA), right atriotomy (RA) and right ventriculotomy (RA) between 1977 and 1981. Six hospital deaths (4.4%) occurred among the 135 patients. Of 41 children with PA, 53 with RA and 41 with RV, one child (1.9%) and 4 children (9.9%) died, respectively. In the trans-PA approach, 8 of 40 children (20%) developed complete right bundle branch block (CRBBB), but there was no occurrence of left axis deviation (LAD), transient complete heart block (CHB) and arrhythmias postoperatively. In the RA approach, 11 of 52 children (21.2%) developed CRBBB and 2 (3.8%) had a combination of LAD and CRBBB. Four of 52 children (7.7%) had a combination of LAD, CRBBB and CHB, but CHB has been treated successfully with medication. Three patients (5.8%) developed arrhythmias, such as junctional rhythm. In the trans-RV approach, 11 of 37 children (29.7%) developed CRBBB and 4 of the 37 (10.8%) had the combination of LAD and CRBBB. Two patients (5.4%) had arrhythmias which disappeared one month after surgery. All incidences of conduction disturbances and arrhythmias after closure of VSD were significantly less in the trans-PA than in the trans-RA or in the trans-RV (p <0.01). However, in the present study, the development of conduction disturbances and postoperative arrhythmias after closure of VSD was not significantly different between the trans-RA and the trans-RV approach.

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This study was designed to investigate the central action of circulating angiotensin II on the regulation of blood pressure in sodium depleted states. The effects of intravertebral arterial infusion of angiotensin II and [Sar-¹, Ala-⁸] angiotensin II (saralasin) on plasma norepinephirne (NE) were studied in α-chloralose anesthetized dogs. Intravertebral arterial infusion of angiotensin II (10 ng/kg/min) increased mean arterial pressure (MAP), heart rate (HR) and plasma NE. Plasma NE was decreased by intravertebral arterial infusion of saralasin (0.40 ± 0.05 to 0.28 ± 0.04 ng/ml, p < 0.05) in normal dogs. The administration of furosemide produced significant increases in plasma NE ( 142.4 ± 23.7%, p < 0.01), plasma renin activity (PRA) (158.6 ± 26.3%, p < 0.01) and HR (32.3 ± 6.0 beats/min, p < 0.01). A slight rise in mean blood pressure (3.9 ± 1.2 mmHg, p < 0.05) was observed during the furosemide administration. Saralasin infused into the vertebral artery significantly suppressed the furosemide-induced increases in plasma NE, HR and PRA, and lowered mean arterial blood pressure. Intravenous infusion of the same dose of saralasin produced no changes in arterial blood pressure, HR and plasma NE. These results suggest that the central sympathetic potentiation induced by circulating angiotensin II may contribute to the regulation of blood pressure in sodium and volume depleted states produced by furosemide.

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We examined the activation patterns in the left ventricular epicardial surface of dog hearts using multielectrode grid during the beats initiating ventricular tachycardia 5 to 120 min after coronary artery occlusion. The grid was placed on the ischemic border zone ( the area was confirmed by ST-isopotential mapping) to record simultaneously 36 unipolar epicardial potentials. Under the control conditions almost radial spread of activation from the central stimulating electrode of the grid was observed. Activation during acute ischemia showed crowded isochrone lines in the ischemic area, especially during the premature beats with shorter coupling intervals. In 8 out of 15 episodes, where ventricular tachycardia was induced by a single premature stimulus, the conduction delay during premature beats culminated in the local conduction block accompanied by circus movement of activation. Subsequent initial beats of ventricular tachycardia also showed similar activation patterns indicating reentry of excitation. In the remaining 7 episodes however, we could not obtain such circus movement of activation under the grid. We also measured the effective refractory period at 5 sites under the grid. The results showed greater dispersion of the effective refractory period in the ischemic border zone throughout 5 to 120 min after coronary occlusion in the cases where ventricular tachycardia developed. These findings suggest that reentry of excitation, which is most probably caused by inhomogeneity of refractoriness in the ischemic border zone, may play an important role in the genesis of ventricular tachyarrhythmias during acute ischemia.

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Cyclic adenosine 3', 5'-monophosphate (cyclic AMP) and adenyl cyclase and phosphodiesterase activities were determined in the specialized myocardial tissue of the conduction system of bovine heart and then compared with those in the ordinary myocardial tissue. The conduction system was comprised of the atrioventricular node (A-V node), the His bundle and the right and the left bundle branches (RBB and LBB). The content of cyclic AMP was higher in the ordinary myocardial tissue than in the specialized myocardial tissue. In the specialized myocardial tissue, its content was highest in the A-V node and lower in the His bundle than in the LBB and the difference between activity as well as the content of cyclic AMP was higher in the ordinary myocardial tissue than in the specialized myocardial tissue. Its activity was higher in the A-V node than in the His bundle or the RBB, and the activities in the His bundle, the RBB and the LBB were similar. Phosphodiesterase activity was higher in the ordinary myocardial tissue than in the A-V node, and the activities in these 4 sections of the conduction system were similar.

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Experimental studies were carried out to compare the efficacy of various agents such as calcium antagonists, phosphodiesterase inhibitors, adrenocorticosteroids, coenzyme Q₁₀ (CoQ₁₀), insulin, beta-blocking agent and reduced glutathion (GSH) on the enhancement of myocardial protection. Eighty-five isolated rabbit hearts were subjected to 2 hours of cardioplegic arrest and maximum developed tension, heart rate, coronary blood flow and coronary arteriovenous oxygen difference following reperfusion were compared between groups pretreated with different agents. The greatest value of maximum developed tension was obtained in the verapamil-treated group (0.2-0.5 mg/kg), followed by dilazep (1 mg/kg), pentoxifylline (30 mg/kg) and CoQ₁₀ (10 mg/kg) treated groups. The time required for the recoveries of spontaneous beating (normal sinus rhythm) on reperfusion was shortest (44± 8 sec) in the group treated with a cardioplegic solution containing a low concentration of betamethasone (0.03-0.05 mg/ml), but the so-called stone hearts and cardiac arrhythmias were most frequently seen in this group. On the contrary, in the group pretreated with calcium antagonists, the time required for the restoration of sinus rhythm was much longer (88-180 sec). Hence, the shortest recovery time was not necessarily associated with a better recovery of myocardial function.

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