The role of hypertension and antihypertensive drugs in cardiovascular complications was evaluated in 380 elderly people living in the Tokyo Metropolitan Gerontology Center. The subjects were classified into four groups according to the presence or absence of hypertension and their antihypertensive treatment, and followed up prospectively for 5 years from 1979 to 1984. The average age of each group was 74 to 76 years. Cerebrovascular disease was observed in 19.3% of male hypertensive and 10.1% of male normotensives (p=0.078). The drug treated group revealed no cerebral hemorrhage and less cerebral infarction. This tendency was not observed in females. Ischemic heart disease was prevalent in the drug treated group (10.9% vs 4.5%, p=0.023) irrespective of blood pressure level. Risk factors such as body mass index, skinfold thickness, serum cholesterol, albumin, creatinine, blood urea nitrogen and uric acid at entry were elevated in the drug treated group. Diuretics were used in 92% of the drug treated group; in 53% as monotherapy and in 39% as combination therapy with other antihypertensive agents. The metabolic effect of diuretics may increase the incidence of ischemic heart disease in the elderly. We might conclude that hypertension in the aged accelerates cerebrovascular complications, and that antihypertensive treatment is effective even in this group. However, the wide use of diuretics could increase the incidence of ischemic heart disease. Careful selection of antihypertensive drugs as well as dose adjustment are needed in the treatment of elderly hypertensive.

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It has been reported that a patient with a trial fibrillation (AF) is in the hypercoagulable state and that this state results in a high incidence of systemic thromboembolisms. In this paper, we have investigated plasma fibrinopeptide a (FPA) levels and the effects of subcutaneous administration of heparin on these levels in patients with AF. Forty-five patients with hypertension (HT) or mitral stenosis (MS) were classified into four groups according to whether they had AF complications; i.e. HT with normal sinus rhythm (NSR), HT with AF, MS with NSR and MS with AF. Patients with AF demonstrated significantly higher plasma FPA levels and lower plasma antithrombin III (AT III) activities than those with NSR. When low dose heparin was administered to patients with AF, plasma FPA levels were decreased to the near normal range, accompanied by an increase in heparin-AT III complex activity and heparin concentration 0.5-1.0 h after injection. These levels were maintained for 5 h. From these results it was concluded that patients with AF were in the hypercoagulable state and that the measurement of plasma FPA levels provided a possibility to detect the underlying activation of blood coagulation.

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To assess the effect of hemodialysis on cardiac function, a change of preload due to water removal was considered. In order to keep the preload constant during hemodialysis extracorporeal ultrafiltration was induced before hemodialysis (step 1), and then hemodialysis without water removal was achieved (step 2). Cardiac performance in 8 patients was evaluated before and at the end of each step using pulsed doppler echocardiography. Step 1: Ultrafiltration was 1350 ± 410 ml and hematocrit increased significantly. Left ventricular end-diastolic dimension (LVDd) decreased from 40.3 ± 4.2 (mean ± standard deviation) mm to 36.1 ± 4.6 mm (p > 0.005) and aortic peak flow velocity (PFV) also decreased from 59.9 ± 16.0 cm/s to 49.0 ± 11.0 cm/s (p > 0.005). Step 2: In contrast, after hemodialysis without water removal, the mean velocity of circumferential fiber shortening (mVcf) increased from 1.36 ± 0.26 circ/s to 1.86 ± 3.6 circ/s (p > 0.005). PFV and average acceleration (Aa) increased from 49.0 ± 11.0 cm/s to 63.8 11.4 cm/s (p 0.001) and from 750 220 cm/s/s to 1270 280 cm/s/s (p > 0.001), respectively. During this step, serum potassium and osmolality decreased significantly. In conclusion, hemodialysis improves cardiac function under constant preload condition and this is due to the direct effects of hemodialysis by the correction of electrolytes and osmolar components such as uremic toxin.

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Late potentials (LPs) were studied using the signal averaging technique in 80 patients with myocardial infarction (MI), idiopathic cardiomyopathy (CM) and idiopathic ventricular tachycardia (IVT). In MI, LP duration was 28.4 ± 12.6 ms in the sustained VT group (I; 8 cases); 18.6 ± 9.0 ms in the nonsustained VT group (II; 11 cases); and 14.4 ± 8.6 ± ms in the non-TV group (III; 21 cases); (p < 0.05 in I vs II, p < 0.01 in I vs III and not significant in II vs III). In CM, it was 33.7 ± 13.0 ms in group I (6 cases); 20.1 ± 5.9 ms in group II (12 cases); and 7.1 ±9.2 ms in group III (14 cases); (p < 0.01 in I vs II, I vs III and II vs III). The LP duration in IVT (8 cases); was 15.6 ± 10.4 ms, which was significantly shorter than that of group I in MI and CM (p < 0.05 vs MI and p < 0.01 vs CM). Late potential duration was also compared between a pacing-inducible VT group and a non-inducible VT group. The mean value of LP duration in the inducible VT group of MI was significantly longer than that in the non-inducible group (27.8 3.9 ms in 4 cases vs 17.3 2.5 ms in 4 cases, p < 0.05). However, there was no significant difference in LP duration between the inducible and non-inducible groups of CM (22.0 11.0 ms in 5 cases vs 22.2 13.6 ms in 5 cases). In IVT, it was 21.0 4.7 ms in 4 cases and 12.8 11.3 ms in 4 cases (n.s.). In conclusion, LP duration was closely related to sustained VT in MI and CM, but not in CM. It is therefore proposed that the pathophysiological significance of LPs is different in each underlying disease.

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The relation of plasma levels of atrial natriuretic peptide (ANP) to those of cyclic 3', 5'-guanosine monophosphate (cGMP) was studied in 43 patients with various heart diseases. Plasma levels of both ANP and cGMP were significantly (p < 0.001) elevated in 34 patients with chronic heart diseases, and a significant positive correlation was observed between the two variables (r = 0.706, 0 < 0.01). Clinical improvement of congestive heart failure resulted in a concomitant decrease in plasma ANP and cGMP levels in 6 patients. In 3 patients with paroxysmal atrial fibrillation, plasma levels of ANP and cGMP increased markedly during arrhythmia. These results indicate that increased circulating ANP may stimulate cGMP production in target cells, which in turn raises plasma levels of cGMP in humans.

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To determine whether low ejection fraction (EF) in mitral stenosis (MS) is the result of depressed contractility or is mediated by other factors, left ventricular (LV) function was analyzed by force-length and stress-shortening relationships. Thirty patients without heart disease served as normal controls (Group 1). Forty-three patients with MS were divided into 2 subgroups: Group 2 (n = 19) had EF within one standard deviation of the mean of Group 1, and Group 3 (n = 24) had EF (Group 2) was associated with low preload (end-diastolic stress) and low afterload (end-systolic stress), and preload and afterload were in the normal range in patients with low EF (Group 3). A significant negative correlation was observed in the whole group of patients with MS between EF and end-systolic stress (Y = -0.14X + 72.8, r = -0.61, p < 0.001), and a positive correlation between end-systolic stress and volume (Y = 1.39X + 65.4, r = 0.45, p < 0.01). These observations suggest that systolic shortening and end-systolic volume of the left ventricle are in part governed by afterload in this disease. It is concluded that low EF of MS is not mediated by reduced preload or inappropriately elevated afterload, and contractility of the ventricle is mildly depressed in MS.

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The study was carried out to ascertain the effects caused by thrombosis in the coronary venous system. The coronary sinus (CS) of 21 adult mongrel dogs was abruptly obstructed to produce acute CS thrombosis. These dogs were then tested for serial changes of ECG, coronary arterial blood flow (CBF), left ventricular pressure (LVP), serum enzymes originating from the injured myocardium and histological changes of myocardium. furthermore, the clinical application of a new coronary venography procedure was investigated. The results obtained in these experiments were as follows; (1) When the CS thrombosis was produced by the abrupt obstruction of the sinus, ECG patterns and serum enzymes originating from the myocardium showed changes similar to those of acute myocardial infarction. (2) The histological examinations showed that the changes in myocardial infarction were characteristically similar to those of hemorrhagic infarction. (3) Despite the complete obstruction of the coronary-venous system by thrombosis, the development of thrombosis or obstruction was not observed on the coronary-arterial side. This phenomenon is probably due to the recirculation of blood flow through the Thebesian vessels. (4) The experiment confirmed that the clear coronary venograms were easily obtained, without any risk, by the fixation of a balloon-tipped catheter inside the CS.

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The purpose of the present study is to determine the role of Na⁺, K⁺-ATPase in adrenergic neurotransmission of hypertension. Isolated perfused mesenteric vasculatures were prepared from spontaneously hypertensive rats (SHR, Okamoto and Aoki, 7-10 weeks old) and age-matched normotensive Wistar Kyoto rats (WKY). The effects of ouabain, a Na⁺, K⁺-ATPase inhibitor, on the norepinephrine overflow from the sympathetic nerve endings were examined. Norepinephrine overflow from the nerve endings as well as pressor responses during electrical nerve stimulation were significantly greater in SHR than in WKY. Ouabain increased the norepinephrine overflow evoked by electrical nerve stimulation, even in the presence of an uptake-blocker of norepinephrine. Further, the facilitatory effect of ouabain on stimulation-induced norepinephrine overflow was more prominent in SHR than in WKY. These results suggested that ouabain-sensitive Na⁺, K⁺-ATP-ase on sympathetic nerve terminals could have an important role in the regulation of neurotransmitter release, and that its activity might be enhanced in SHR compared with WKY.

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The partial agonist activity of xamoterol was evaluated by measuring changes in heart rate (HR) in pithed rats. Xamoterol showed dose-dependent positive chronotropic effects in catecholamine-depleted pithed rats (HR: 199 ± 6 beats/min) and dose-dependent negative chronotropic effects in sympathetic nerve-stimulated pithed rats (HR: 325 ±16 beats/min). In contrast, isoproterenol exerted dose-dependent positive chronotropic effects in either condition (HR: 189 ± 7 and 332 ± 5 beats/ min) and propranolol exerted dose-dependent negative chronotropic effects in either condition (HR: 209 ± 5 and 344 ± 19 beats/min). When exogenous noradrenaline was continuously infused into catecholamine-depleted pithed rats, xamoterol showed doserelated positive chronotropic effects with noradrenaline at 0.5 μg/(kg min) (HR: 330 ± 5 beats/min). During continuous infusion of xamoterol [100 ng/(kg min)] into pithed rats, the control HR before stimulation was increased and the maximum increase produced by the sympathetic nerve stimuli at 0.25 to 4 Hz decreased. The maximum increase in HR brought about by xamoterol was about 71% of that induced by isoproterenol, and those by pindolol and practolol were about 40% and 21% respectively. It is concluded that xamoterol is a partial agonist with a strong agonist action.

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This study investigated the effects of a thromboxane synthetase inhibitor (OKY-046) and a cyclooxygenase inhibitor (ketoprofen) on hypoxic pulmonary vasoconstriction in conscious adult sheep in order to evaluate the physiological role of thromboxane and other cyclooxygenase products. In addition, we studied the effects of histamine H₁ (chlorpheniramine) and H₂ antagonists (cimetidine) on hypoxic pulmonary vascular tone. Hypoxia caused a 37% rise in pulmonary arterial pressure (p < 0.05) and a 36% increase in pulmonary vascular resistance (p < 0.05). Pretreatment with intravenous OKY-046 10 mg /kg or ketoprofen 2 mg/kg had no effect on normoxic pulmonary vascular tone and inhibited the increase in plasma TXB₂ concentration during hypoxia without affecting the pulmonary pressor response to hypoxia. Cimetidine produced an increase in hypoxic pulmonary pressor response to hypoxia. Cimetidine produced an increase in hypoxic pulmonary vascular tone when individual members of the group were compared, but there was no statistically significant difference when the group was compared to the control study. Chlorpheniramine had no effect on hypoxic pulmonary tone. These data suggest that hypoxic pulmonary vasconstriction is not mediated by release of TXA₂, that hypoxic vascular tone is not modulated by cyclooxygenase products, and that the histamine H₂ receptor may play a modulating role in hypoxic pulmonary vasconstriction in conscious adult sheep.

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The effect of pretreatment with heparin on coronary thrombolysis by plasminogen pro-activator was studied in 20 dogs with a 1-h old clot in the left anterior descending coronary artery. The clot was induced by placement of a copper coil and thrombolysis was confirmed angiographically. Intravenous administration of plasminogen pro-activator at a rate of 5 μg/kg/min (group 1; n = 5) and 20 μg/kg/min (group 2; n = 5) after pretreatment with heparin (300 IU/kg) induced thrombolysis in 31 ± 4 min and 14 ± 2 min, respectively. When plasminogen pro-activator was administrated intravenously at a rate of 20 μg/kg/min without heparin pretreatment (group 3; n = 5), the infusion interval for successful thrombolysis was prolonged to 45 ± 6 min, which was significantly longer than that in groups 1 and 2 (p < 0.001). In these three treatment groups, thrombolysis was not associated with severe alteration in plasma hemostatic factors (fibrinogen and alpha₂-antiplasmin). An evaluation of plasma urokinase activities using a chromogenic substrate S-2444 did not showed that heparin increased the plasma urokinase activities. By increasing the dose of plasminogen pro-activities. By increasing the dose of plasminogen pro-activator to 80 g/kg/min, successful reperfusion was rapidly obtained in 25 5 min without heparin pretreatment (group 4; n = 5); this was significantly faster than the results seen in group 3 (p <0.001). An analysis of urokinase activities showed that plasminogen pro-activator was fully converted to urokinase, which induced complete depletion of fibrinogen and alpha₂-antiplasmin. These results suggest that heparin can enhance coronary thrombolysis in dogs and the mechanism of the enhancement is not related to the plasma urokinase activities. In addition, heparin may reduce the risk of the depletion of plasma fibrinogen by lowering the doses of plasminogen pro-activator necessary for reperfusion.

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A 54-year-old man presented with continual angina pectoris at rest, associated with an anomalous coronary artery. He also had an aneurysm at the submitral region of the left ventricular postero-lateral wall, without evidence or prior myocardial infarction, which showed hypokinetic inward motion during systole. We assume that this was a rare case of left ventricular aneurysm without prior myocardial infarction, the etiology which might related to the anomalous coronary artery.

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A large right ventricular aneurysm was detected by an echocardiographic examination in a 50-year-old woman presenting with weakness, collapse and hypotension. At surgery, another smaller aneurysm, arising from the anterior infundibulum of the right ventricle, was found in addition to the large one. Both were resected. Histological studies on the resected specimen revealed that much of the myocardium was replaced by adipose tissue. As far as we know this is the first reported case in Japan in which two congenital aneurysms arose from the right ventricle as a result of muscular defect.

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We describe two cases of left atrial myxoma, demonstrating an unusual tumor vascularity as revealed by coronary angiograms. Both cases had suffered typical episodes of transient ischemic attack (TIA). Coronary angiography revealed tumor blood supply from coronary arteries in both cases, and also a leakage of contrast medium from the surface of the tumor blood vessels to the left atrium in one case. In the medical literature available in English reviewed so far, no report of such a leakage has been reported. Selective coronary arteriography can be a useful diagnostic method of delineating left atrial myxoma and its blood supply.

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Immunological identification of lymphocyte subsets in a patient with myocarditis revealed an increase in myocardial OKT 11 (pan T), OKT 4 (inducer/helper T) and OKT 8 (suppressor/cytotoxic T) subsets associated with a transient decrease in the percentage of circulating OKT 3 (pan T) and OKT 4 (inducer/helper T) subsets. This decrease may be explained by the accumulation of these subsets in the diseased myocardium. Specific antigenic markers on lymphocytes at the site of myocardial differ from those on corresponding peripheral lymphocytes. This observation may highlight the immuno-pathogenetic mechanisms involved in the development of myocarditis.

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