Takio Shimamoto

Directional Difference of Conduction Velocity in the Cardiac Ventricular Syncytium Studied by Microelectrodes

In the theory of electrocardiography the direction of myocardial fibers has been almost ignored. In order to evaluate whether this is proper or not, directional difference of conduction velocity in the ventricular syncytium was examined by capillary microelectrodes. Conduction velocity in the direction of myocardial fibers was found to be usually several times larger than that vertical to them. This difference is significantly large and cannot be ignored even though rapidity of conduction through Purkinje fibers is considered. This statement became more applicable in various abnormal conditions. Thus it is concluded that the direction of myocardial fibers should be given more attention in discussion of propagation of excitation waves in the cardiac ventricle.

Atherosclerosis-inhibiting effect of an antibradykinin agent, pyridinolcarbamate

Abstract An antibradykinin and antilysylbradykinin agent, pyridinolcarbamate (2,6-bis-hydroxymethylpyridine- bis N- methylcarbamate), has a potent preventive effect on the edematous arterial reaction, and has been shown to possess an antiatherogenic property on the basis of the results obtained in the present series of experiments with 118 rabbits. The feeding of a high-cholesterol diet to the animals over a prolonged period of 13 to 15 weeks was employed to induce the experimental atherosclerosis, and the daily administration of pyridinolcarbamate in doses of 5 and 10 mg. per kilogram was shown to exert a powerful effect in preventing the apperance of atheromatous changes (p The antiatherogenic property of this compound is not related to an influence on the level of cholesterol in the blood; in fact, hypercholesterolemia is not depressed by the drug. The antiatherogenic property has been presumed to correlate possibly with the kinin-antagonistic effect of this compound.

Ventricular Fibrillation Studied by the Microelectrode Method

Capillary ultramicroelectrodes were inserted into ventricular muscle fibers of dogs in ventricular fibrillation and action potentials obtained were compared with deflections of unipolar direct lead, adjoining bipolar direct lead or other electrocardiograms taken simultaneously. In most stages of ventricular fibrillation neither synehronism nor any other regular time relationship could he found between them. Microelectrodes inserted at two points variously distant on various regions of the ventricular surface also failed to show any regular time relationship. Total incoordination of ventricular muscle fibers was thus supported.

Hypersecretion of estrogen in Takayasu's disease

Abstract The 24 hour urinary excretion of total estrogens was measured by the methods of Cohen, 17 Brown, 18 and Nishi 19 in 20 healthy women aged 18 to 45 (mean 31.8 ± 6.8) and in 20 patients with typical Takayasus disease aged 18 to 45 (mean 32.2 ± 7.8) during the follicular and luteal periods, respectively. A continuous high level of urinary excretion of total estrogens without normal biphasic rhythm was found in those with Takayasus disease. The 24 hour urinary excretion of total estrogens during the follicular period was 7.4 ± 0.8 μg per day in the control subjects and 13.7 ± 1.4 μg per day in the patients; the difference was statistically significant (p The continuous high level of urinary excretion of total estrogens found in this study has been discussed as one possible explanation of the characteristic localization of this morbid condition in the arterial system.

SCANNING AND TRANSMISSION ELECTRON MICROSCOPIC OBSERVATION OF ENDOTHELIAL CELLS IN THE NORMAL CONDITION AND IN INITIAL STAGES OF ATHEROSCLEROSIS

The fine structures of vascular endothelial surface with linear endothelial folds, were clearly shown by scanning and transmission electron microscopes in large arteries and veins of man and other mammals and the nuclear parts of endothelial cells were shown in the gullies in scanning electron microscopical observation.

EXPERIMENTAL STUDY ON ATHEROSCLEROSIS –AN ATTEMPT AT ITS PREVENTION AND TREATMENT

Electron microscopical analysis of endothelial linings of the aortic lumen and of the vasa vasorum was made in man, rhesus monkey, dog, rabbit, rat, chicken and pigeon with reference to permeability of the arterial wall, because cholesterol and other substances accumulating in atheromatous lesions have been known to be transported mainly by infiltration into the lesions from the blood stream across the endothelial lining. Porous capillaries were found in vasa vasorum of man, rabbit and pigeon and a well developed vacuole system in the endothelial cells of man and chicken. For the present experiment of atherosclerosis the rabbit has been chosen.

Hyperreactive Arterial Endothelial Cells in Atherogenesis and Cyclic AMP Phosphodiesterase Inhibitor in Prevention and Treatment of Atherosclerotic Disorders

The hyperreactive arterial endothelial cells have been introduced in this paper. They are characterized by their ability to transport particles too large for the small holes of the internal elastic lamina locating underneath the endothelial cells, such as carbon particles with the similar size of LDL, floating beta-lipoprotein, Lp(a) and especially of VLDL, into the subendothelial space from the blood stream by their abnormally strong contracting and phagocytosis-like activity. Large particles such as carbon particles with a size of 200 to 700 angstrom are too large to penetrate further through holes of the internal elastic lamina from the subendothelial space to muscular layers of the arterial wall, resulting in stagnating for a long time in the subendothelial space, thus showing the atherogenic property of the hyperreactive arterial endothelial cells. Such endothelial cells appear spotty and streaky in the localized endothelial lining of predominantly susceptible parts to atherosclerosis in susceptible animal species such as rabbit, chicken, and rhesus monkey especially densely in their atheromatous lesions, but do not generally appear in non-susceptible animals to atherosclerosis like rate and dog. They are extremely few in infant rabbit, but increase by age.They appear in hypertensive rat, showing a characteristic distribution even in small groups of arteriessuch as the circle of Willis. Cyclic AMP, and especially dibutyryl cyclic AMP, exhibited an inhibitory effect on the hyperreactivity of those cells. Cyclic AMP phosphodiesterase inhibitors, EG467 and eg626, exhibited a powerful inhibitory effect on the contracting and phagocytosis-like activity of those cells, as in the case of pyridinolcarbamate, which enhances enzymes to produce ATP and inhibits slightly cyclic AMP phosphodiesterase, although its inhibitory effect on cyclic AMP phosphodiesterase is weaker than that of EF467 and EG626. The usefulness of the inhibitors on cyclic AMP phospodiesterase of arterial endothelial cells and platelets and on that of brain, such as EG467 AND EG626, has been suggested in the treatment of atherosclerotic disorders, especially of cerebral atherosclerosis. Some of the hitherto desperate mental disability of the aged seem to be a promising target for treatment with cyclic AMP phosphodiesterase inhibitors.

Microassay of cyclic nucleotides in vessel wall: I. Cyclic AMP

Abstract The levels of cyclic adenosine 3′,5′-monophosphate (cyclic AMP) in the aortic intima and media of man and other species were measured microbiochemically by Lowrys quantitative histochemical technique and Gilmans competitive protein binding assay. Rather high levels of cAMP were found in the intima of all species examined as compared with that in the media. The role of cAMP in intima is discussed in relation to atherogenesis.

Release of a Thromboplastic Substance from Arterial Walls by Epinephrine

Aortic preparations of 70 rabbits including the vasa vasorum were perfused in vitro by oxygenated saline under a pressure of 100 mm Hg. The main branches of the aorta were ligated and the perfusate, which irrigates the aortic lumen, but not the vasa vasorum, was sampled every minute. The samples were assayed for thromboplastic activity by means of the calcium clotting time. The calcium clotting time was shortened significantly in samples taken one, two, and three minutes after injection of 0.005 μg epinephrine. The response was present in perfusing with Tyrodes solution as well as with 0.9% NaCl but was absent if oxygen was withheld from the solution. Larger dose of epinephrine (0.05 μg) caused an initial shortening of the calcium clotting time, followed by a prolongation in two out of five cases. Still larger doses (0.5 μg) or much smaller ones (0.0005 μg) were without effect. In the aortas of rabbits which were pretreated by 5 mg/kg of nialamide two hours before removing the aorta, the previously mentioned effect of epinephrine was prevented. However, direct perfusion of the aortic preparation by a nialamide mixture in vitro did not prevent the release of thromboplastic active substance by epinephrine. Norepinephrine in doses of 0.005, 0.05, and 0.5 μg was found to be ineffective. These observations may explain the effects of epinephrine on the clotting time of blood originally described by Cannon and Gray.5

HYPERREACTIVE ARTERIAL ENDOTHELIAL CELLS: A CLUE FOR THE TREATMENT OF ATHEROSCLEROSIS

Arterial endothelial cells, which are capable of phagocytizing carbon particles of the same size as beta- and pre-beta-lipoprotein, were found only in endothelial cells of arterial segments susceptible to atheromatous changes in susceptible animal species, and the distribution closely corresponded to the susceptibility. The distribution of such endothelial cells is dense in large arteries, in the openings to their branches, especially in downstream portions, of rabbits, hens, and cocks; however, the distribution is relatively scanty in arteries of rhesus monkeys and is very scanty in dogs. Carbon particles were also rare in the suckling rabbit and tended to increase with age. They were not found in Wistar rats but were found in spontaneously hypertensive rats, which showed a characteristically diffuse distribution, even in relatively small arteries. The carbon particles, phagocytized, were released to the subendothelial space but were difficult to pass through the internal elastic lamina and tended to stagnate there for more than one month. The authors therefore call these cells hyperreactive endothelial cells. Various vasoactive substances, such as angiotensin II, histamine, and serotonin, significantly enhanced the phagocytic activities of arotic endothelial cells in rabbits; epinephrine and norepinephrine also slightly enhanced these activities. Various smooth muscle relaxants, such as ATP, pyridinol carbamate (ATP synthesis-enhancing substance), cycli-AMP, dibutyryl cycli-AMP, phthalazinol (cyclic-AMP phosphodiesterase inhibitor), iproveratril (calcium entry-inhibiting substance), colchicine, and vinblastine, with their different modes of action, commonly inhibited phagocytic activities, a finding that suggests a significant role for contractile protein in the permeability problem of atherogenesis. The atheromatous lesions of cholesterol-fed rabbits exhibited a striking increase in hyperreactive endothelial cells, accompanied by a marked rise in the activity of low-Km cyclic-AMP phosphodiesterase activity in atheromatous lesions and adjacent muscular layers, especially in rabbits with rapidly progressing atheroma.