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Biomedical subjects

Y Kusama

Publications and source records attributed to Y Kusama.

At least 55 records · Page 3Linked to original sources
PubMed1992

Diabetes and susceptibility to reperfusion-induced ventricular arrhythmias.

Studies using chemically-induced models of diabetes have shown the diabetic myocardium to exhibit abnormalities in cellular ion transport, which may affect susceptibility to reperfusion-induced arrhythmias. We studied the incidence of reperfusion-induced ventricular tachycardia (VT) and fibrillation (VF) in isolated hearts from rats with streptozotocin-induced diabetes and from age-matched and weight-matched control rats (n = 12 per group). Following 5 min of regional ischaemia, reperfusion resulted in a similarly low incidence of arrhythmias in all three groups. Following 10 min of regional ischaemia, the incidence of VT was 92, 100 and 92%, and the incidence of VF was 75, 92 and 92% in diabetic, age-matched control and weight-matched control groups, respectively (NS). However, among those hearts which exhibited VF, the incidence of sustained (greater than or equal to 120 s) VF was 73 and 55% in age-matched and weight-matched control groups, respectively, and 0% in the diabetic group (P less than 0.05 vs both controls). The mean duration of VF in the diabetic group was reduced from 201 +/- 33 and 171 +/- 36 s in age-matched and weight-matched control groups, respectively, to 9 +/- 3 s (P less than 0.05). Thus, streptozotocin-induced diabetes in the rat does not result in an increased susceptibility to reperfusion-induced arrhythmias. To the contrary, hearts from diabetic rats are less susceptible to potentially lethal arrhythmias during reperfusion. Likely contributory factors to this phenomenon include (i) increased myocardial content of free radical scavenging enzymes, (ii) prolonged action potential duration, and (iii) reduced activity of sarcolemmal Na+/H+ and Na+/Ca2+ exchange processes, all of which have previously been reported in similar models of diabetes.

Animals↗
PubMed1992

Two cases of variant form angina pectoris associated with myocardial bridge--a possible relationship among coronary vasospasm, atherosclerosis and myocardial bridge.

Myocardial bridge (MB) is a congenital anomaly of the coronary artery and may occur in 5 to 12% of the human population. However, the mechanism of MB-induced myocardial ischemia is still speculative. We report 2 cases of variant form angina pectoris associated with MB in which myocardial ischemia seemed to be related to the interaction between coronary perfusion and MB. In case 1, electrocardiography during anginal attack at rest showed ST elevation in the inferior leads and MB was observed after percutaneous transluminal coronary angioplasty at the site of the right coronary artery lesion following successful dilatation. In case 2, MB of the left anterior descending coronary was located in the identical portion where coronary vasospasm was induced by intracoronary acetylcholine injection, although ischemia during the spontaneous anginal attack was limited to the inferior area of myocardium. These 2 cases suggest that MB can be, at least in some patients, one of the possible causes of the endothelial damage which seems to be related to coronary vasospasm; this was documented in both cases.

Angina Pectoris, Variant↗
PubMed1991

Pharmacological studies of arrhythmias induced by rose bengal photoactivation.

Singlet oxygen and superoxide production by rose bengal photoactivation leads to rapid electrophysiological changes and arrhythmias. To investigate which intermediate is causative and to probe possible mechanisms, hearts (n = at least 6/group) were perfused aerobically for 10 min without rose bengal followed by 5 min with rose bengal before illumination for 20 min. In controls, all or most hearts exhibited ventricular premature beats, ventricular tachycardia, and complete atrioventricular block. Most antioxidants tested had no protective effect; histidine, however, significantly delayed the onset of electrocardiographic (ECG) changes. In further studies, two antiarrhythmic agents (quinidine and verapamil) had no little protective effect, whereas R56865 significantly delayed the onset of ECG changes and reduced the incidence of arrhythmias. However, spectrophotometric and laser pulse radiolysis studies showed that this apparent protective effect might have resulted from an interaction between R56865 and the rose bengal molecule, leading to a reduction in singlet oxygen production. In conclusion, the electrophysiological changes induced by rose bengal photoactivation are likely to be due to singlet oxygen; antiarrhythmic drugs appear to be unable to protect against the injury unless there is some interaction with the photoactivation process.

Animals↗
PubMed1991

Reactive oxygen species modify the structure and function of the cardiac sarcoplasmic reticulum calcium-release channel.

Restoration of blood flow to the ischemic myocardium prevents continuing cell necrosis, but reperfusion may cause irreversible damage to potentially salvable tissue, possibly through the generation of toxic reactive oxygen species. Intracellular calcium overload, secondary to membrane lipid peroxidation, has been proposed as a general pathogenic mechanism. However, using the photosensitisation of rose bengal to generate singlet oxygen and superoxide radicals, we demonstrate a direct effect of reactive oxygen species on the cardiac sarcoplasmic reticulum calcium-release channel. Exposure of heavy sarcoplasmic reticulum vesicles to reactive oxygen species in vitro resulted in the progressive loss of specific [3H]ryanodine binding and the degradation of high molecular weight proteins identified by polyacrylamide gel electrophoresis. The gating of single channels incorporated into artificial planar phospholipid bilayers was modified during the exposure to reactive oxygen species: an initial increase in open probability being followed by irreversible loss of channel function. Degradation by reactive oxygen species of specific proteins, such as the calcium-release channel, may contribute to in vivo reperfusion injury.

Animals↗
PubMed1990

Singlet oxygen and myocardial injury: ultrastructural, cytochemical and electrocardiographic consequences of photoactivation of rose bengal.

Photoactivation of rose bengal leads to the generation of reactive oxygen intermediates (predominantly singlet oxygen with some superoxide anion) which are potentially injurious to biological systems. Isolated rat hearts were perfused aerobically at 37 degrees C with bicarbonate buffer for 10 min without rose bengal and for 10 min with rose bengal (500 nM). During the last 5 min of perfusion with rose bengal, hearts were globally illuminated (5500 lux) with light (530 to 590 nm) and electrocardiographic changes were detected within 2.7 +/- 0.3 s (approximately 15 beats) of the onset of illumination. All hearts developed ventricular premature beats, ventricular tachycardia and complete atrioventricular block after 20.2 +/- 6.6, 68.0 +/- 29.7 and 184.3 +/- 20.9 s, respectively. Photoactivation by rose bengal also resulted in severe ultrastructural damage including intracellular clarifications, swelling of mitochondria with disruption and clumping of cristae and the development of contraction band necrosis. Extensive degranulation of mast cells was also observed. These changes were most evident in myocytes adjacent to large epicardial blood vessels. Cytochemical studies demonstrated that there was a loss of the calcium which is normally localized at the inner sarcolemmal surface, and the appearance of intramitochondrial calcium precipitates. In control hearts (no illumination and/or no rose bengal), arrhythmias did not develop and tissue morphology and calcium distribution remained normal. In additional studies, rose bengal-perfused hearts were illuminated regionally for 10 min over an area (approximately 6 mm2) of the left ventricle. Extensive tissue injury and calcium overload developed in the area of maximum illumination.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

Photoactivation of porphyrins: studies of reactive oxygen intermediates and arrhythmogenesis in the aerobic rat heart.

STUDY OBJECTIVE: In situ production of reactive oxygen intermediates (singlet oxygen and superoxide) during the photoactivation of rose bengal can induce arrhythmias in the aerobically perfused rat heart. The present study was undertaken (1) to assess whether these effects occur with other photosensitizers; (2) to identify the injurious intermediates; (3) to probe the site of action of these phenomena. DESIGN - The study involved the use of meso-tetra-(4-sulphonatophenyl)-porphine (TPPS), a porphyrin which, in contrast to rose bengal, promotes the production of singlet oxygen alone when illuminated. After 10 min of TPPS free perfusion, rat hearts (n = 6 per group) were perfused aerobically with TPPS (1, 5, 10 or 50 mumol.litre-1) for 25 min; during the last 20 min, the hearts were illuminated (3600 lux). In additional studies, TPPS (50 mumol.litre-1) was washed out before illumination. EXPERIMENTAL MATERIAL: Hearts from 30 male Wistar rats, weighing 220-280 g, were excised and perfused retrogradely. MEASUREMENTS AND MAIN RESULTS: Cardiac function was unaffected with TPPS alone. Upon illumination, electrocardiographic changes (increase in QT interval and/or T wave changes) and arrhythmias developed in a dose dependent manner. At the highest dose, electrocardiographic changes occurred within 7.0(SEM 0.4) s; all hearts exhibited ventricular premature beats and complete atrioventricular block; 67% developed ventricular tachycardia and 17% ventricular fibrillation. During illumination, hearts also exhibited a dose and time dependent decrease in coronary flow. In additional studies, despite the absence of TPPS in the perfusate, all hearts exhibited complete atrioventricular block, 67% developed ventricular premature beats and 33% ventricular tachycardia; none exhibited ventricular fibrillation. CONCLUSIONS: The results suggest that singlet oxygen, as opposed to superoxide, is responsible for the injury which occurs at tissue surfaces to which photosensitizer is bound.

Animals↗
PubMed1990

Exacerbation of reperfusion arrhythmias by sudden oxidant stress.

A burst of free oxygen radical production has been demonstrated during the early moments of reperfusion, coincident with the onset of reperfusion arrhythmias, which can be attenuated by antioxidants. We have investigated whether a sudden burst of oxidant stress, superimposed on that occurring during reperfusion, can exacerbate reperfusion arrhythmias. Rat hearts (n = 12/group) were subjected to 12 minutes of aerobic perfusion; during the last 2 minutes, rose bengal (1 mumol/l) was added to the perfusion fluid. Then, regional ischemia was induced, and rose bengal-free perfusion was restored. After 5 minutes of ischemia, reperfusion was initiated for 5 minutes, and during the first 30 seconds of reperfusion, hearts were uniformly illuminated (8,500 lux) with green light (530-590 nm). The photoactivation of rose bengal trapped in the tissue, producing singlet oxygen and superoxide, resulted in an exacerbation of reperfusion arrhythmias. Thus, 92% of hearts developed ventricular premature beats, 83% ventricular tachycardia, and 33% ventricular fibrillation. In contrast, hearts with regional ischemia and reperfusion in the absence of rose bengal and/or illumination did not develop ventricular fibrillation; only one heart exhibited ventricular tachycardia, and the incidence of ventricular premature beats was lower (42-50%). Furthermore, the burst of oxidant stress shortened the time to onset of ventricular premature beats from 21.7 +/- 5.6 to 9.9 +/- 2.1 seconds. Additional studies revealed that rose bengal photoactivation without reperfusion was less arrhythmogenic compared with the combination of reperfusion plus photoactivation. These results demonstrate that a sudden burst of oxidant stress during the early moments of reperfusion can exacerbate the vulnerability to reperfusion arrhythmias.

Animals↗
PubMed1990

Angiographic response to a vasodilating drug, nicorandil, in patients with coronary artery disease.

To investigate the usefulness of nicorandil as an antianginal drug, we compared the coronary vasodilatory response in nonstenotic coronary artery segments and the hemodynamic response in 26 coronary artery disease patients. Both responses were studied prior to sublingual administration of 10 mg of this drug and 10, 30 and 60 min afterward. The plasma nicorandil concentration was determined up to 120 min after administration. The mean coronary dilating ratio of nicorandil was 117% 30 min after administration (p less than 0.01) and showed a good correlation to the plasma nicorandil concentration. The mean maximum dilating ratio of each patient was 125%. There was no difference between individual coronary arteries or between proximal and distal segments in terms of the coronary artery dilating ratio. The plasma nicorandil concentration required for 120% dilation of the coronary arteries was 26 ng/ml, 89 ng/ml and 142 ng/ml for those cases with variant angina, exertional angina and postinfarction angina, respectively. Hemodynamic changes due to administration of this drug included a decrease in blood pressure, and a reduction in total peripheral resistance, rate-pressure product, pulmonary capillary pressure and stroke-work index. These results indicate that the antianginal effects of nicorandil are derived from its coronary vasodilatory action and an inhibitory effect on myocardial oxygen consumption.

Administration, Sublingual↗
PubMed1990

[Evaluation of diffuse lung uptake of 201Tl in bronchopulmonary diseases].

201Tl scintigraphy was performed in various bronchopulmonary diseases. Applying semiquantitative and visual assessments of grade of 201Tl was observed in various broncho-pulmonary diseases with multiple or numerous abnormal shadows in the lung fields, and obvious lung uptake was also shown even in some cases with few or no abnormal shadows. Positive results of moderate and marked lung uptake of 201Tl more than 60.0% were obtained in diffuse interstitial pneumonia, hypersensitivity pneumonitis, silicosis, the disseminated type of pulmonary tuberculosis and primary lung cancer. The ratio of radioactivity of the lung (maximum) to the upper mediastinum was 1.04 +/- 0.24 in healthy controls, and more than 2.0 in diffuse interstitial pneumonia, hypersensitivity pneumonitis and silicosis. The ratio of radioactivity of the right lung to the administered dose of 201Tl was 1.5 +/- 0.9% in healthy controls, and more than 3.0% in diffuse interstitial pneumonia, silicosis, the disseminated type of pulmonary tuberculosis and primary lung cancer. Lung uptake of 201Tl was diffuse, homogeneous and marked in diffuse interstitial pneumonia and hypersensitivity pneumonitis, while it was scattered and slight in chronic obstructive lung diseases. 201Tl scintigraphy seems to be useful for detecting interstitial disorders of the lung including edema, inflammatory and granulomatous changes, especially in cases with slightly abnormal or normal chest X-ray films.

Aged↗
PubMed1990

[Clinical significance of 201Tl lung uptake in heart diseases].

In order to evaluate the clinical significance of 201Tl lung uptake, 201Tl myocardial scintigraphy was performed in 675 cases with various cardiac diseases. The lung uptake ratio of 201Tl (L/T) was calculated by ratio of the total radioactivity of the unilateral lung to the injected dose of 201Tl in 69 cases. Using both 201Tl scintigraphy and cardiac pool scintigraphy with 99mTc-human serum albumin, images of 201Tl of the intravascular space and extravascular space were obtained in 14 cases. The image of 201Tl of the extravascular space was almost the same as the original 201Tl image as regards the pattern of 201Tl-distribution, and the lung uptake ratio of the former was 95.7 +/- 2.8% of that of the latter. The mean values of L/T of the right and left lung were 1.5 +/- 0.9%, 1.2 +/- 0.6% in the healthy lungs, 2.8 +/- 1.4% and 1.4 +/- 0.7% in heart diseases without left heart failure, and 4.4 +/- 1.8% and 2.6 +/- 1.2% in those with left heart failure, respectively. Increased lung uptake ratio of 201Tl, which was related to post-capillary pulmonary hypertension, prolonged pulmonary circulation time and findings of left heart failure, was observed more frequently in mitral valvular diseases (72.2%) and dilated cardiomyopathies (60.0%). Increased lung uptake of 201Tl was associated with normal or increased pulmonary perfusion in many cases or areas, but with pulmonary hypoperfusion in some cases with post-capillary pulmonary hypertension, in whom both increased lung uptake of 201Tl and pulmonary hypoperfusion were shown in the lower lung fields.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Output↗
PubMed1989

Growth and morphogenesis of mouse prostate epithelial cells in collagen gel matrix culture.

Epithelial cells were isolated from the ventral prostate gland of the mouse after prolonged incubation in a mixture of collagenase, Dispase and hyaluronidase followed by extensive pipetting. The isolated epithelial cells were then embedded in collagen gels. After cultivation in Dulbecco's modified Eagle's medium supplemented with fetal bovine serum, epidermal growth factor, 5 alpha-dihydrotestosterone and cortisol, stimulation of growth and branching morphogenesis of the epithelial cells were observed. Under these culture conditions, growth of contaminating fibroblastic cells was rarely seen. These observations suggest that hormones including androgen directly stimulate the growth and morphogenesis of mouse prostate epithelial cells in culture.

Androgens↗
PubMed1989

Singlet oxygen-induced arrhythmias. Dose- and light-response studies for photoactivation of rose bengal in the rat heart.

In a study of aerobically perfused rat hearts, the in situ photoactivation (530-590 nm) of rose bengal (a process that leads to the production of singlet oxygen and superoxide) has been shown to lead to the rapid development of electrocardiographic abnormalities and arrhythmias. With rose bengal concentrations of 1,000, 500, 250, 100, and 50 nmol/l (n = 6/group), photoactivation (3,600 lx) led to electrocardiographic changes (inversion of the T wave, Q-T prolongation, or both) after 3.8 +/- 0.9, 4.5 +/- 0.7, 11.8 +/- 2.1, 24.8 +/- 3.9, and 65.3 +/- 6.0 seconds), respectively; ventricular premature beats occurred in 100% of hearts after 0.5 +/- 0.2, 1.1 +/- 0.3, 2.2 +/- 0.7, 4.4 +/- 0.8, and 6.6 +/- 1.2 minutes, respectively. Ventricular tachycardia occurred in 83%, 83%, 83%, 67%, and 50% of hearts after 2.1 +/- 0.2, 2.1 +/- 0.4, 2.8 +/- 0.7, 5.7 +/- 2.0, and 11.2 +/- 1.9 minutes, respectively, and complete atrioventricular block in 100%, 100%, 100%, 100%, and 67% of hearts after 3.8 +/- 0.7, 6.5 +/- 1.0, 5.5 +/- 0.9, 13.8 +/- 1.0, and 14.1 +/- 0.9 minutes, respectively. With a fixed concentration (250 nmol/l) of rose bengal, similar light-response relations were observed. Photoactivation of rose bengal had no effect on heart rate but caused a transient (0-4 minutes) vasodilation followed by a progressive vasoconstriction. In further studies in which rose bengal was washed out for 10 minutes before photoactivation, several arrhythmias still developed, indicating that rose bengal binds strongly to tissue and acts as a cellular level rather than in the vascular compartment. To assess the reversibility of rose bengal-induced effects, hearts (n = 6/group) were perfused with rose bengal (250 nmol/l) for 1, 2, 4, 6, and 20 minutes followed by perfusion in the dark for 19, 18, 16, 14, and 0 minutes, respectively. During dark perfusion, the incidence of arrhythmias declined and any decrease in coronary flow was reversed. However, analysis of contents of adenosine triphosphate, creatine phosphate, lactate, and creatine kinase leakage indicated the occurrence of severe injury that did not abate on termination of photoactivation. Finally, although many arrhythmias developed before the onset of vasoconstriction, the reduction in flow with consequent ischemia was shown to exacerbate vulnerability to arrhythmias. In conclusion, short-lived reactive oxygen intermediates such as singlet oxygen and superoxide, which are produced during the photoactivation of rose bengal, can cause rapid and major damage to the heart and its function.

Animals↗
PubMed1989

Rapid electrophysiological changes leading to arrhythmias in the aerobic rat heart. Photosensitization studies with rose bengal-derived reactive oxygen intermediates.

The objective of this study was to determine whether reactive oxygen intermediates (e.g., singlet oxygen and the superoxide radical) can rapidly induce electrophysiological disturbances leading to the genesis of arrhythmias, even in the absence of ischemia and reperfusion. Rat hearts (n = 6 per group) were perfused aerobically at 37 degrees C for 10 minutes without rose bengal and for 5 minutes with rose bengal (250 nmol/l), during which time no changes in coronary flow or heart rate were observed. Hearts were then uniformly illuminated for 20 minutes with green light (530-590 nm) from 200 fiber optic cables. With light and without rose bengal, or vice versa, all hearts remained stable. However, in the illuminated rose bengal group, electrophysiological changes (inversion of the terminal portion of the T wave and an increase in Q-T interval) were observed within 11.8 +/- 2.1 seconds (i.e., less than 60 beats). All hearts exhibited ventricular premature beats (within 2.2 +/- 0.7 minutes) and ventricular tachycardia (within 2.8 +/- 0.7 minutes) before the occurrence of complete atrioventricular block (within 5.5 +/- 0.9 minutes). During the illumination period, coronary flow progressively fell in the rose bengal-perfused hearts from 11.6 +/- 0.5 ml/min to 2.0 +/- 0.4 ml/min (p less than 0.05 when compared with any control group). When a similar progressive reduction in coronary flow was mimicked (with or without rose bengal), no arrhythmias occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

Aerobiosis↗
PubMed1989

Characteristics of symptomatic and asymptomatic myocardial ischemia during ambulatory electrocardiographic monitoring in patients with angina pectoris.

The purpose of the present study was to clarify the characteristics of myocardial ischemic attacks in patients with exertional angina (EA, 56 cases), exertional and rest angina (ERA, 28 cases), rest angina (RA, 4 cases), and variant angina (VA, 39 cases). The Holter electrocardiographic findings were compared among the four types of angina pectoris. The frequency of symptomatic ischemic attacks in descending order was 46.0% in EA, 29.0% in ERA, 28.1% in RA, and 21.6% in VA, while the frequency of asymptomatic ischemic attacks was in the reverse order. The maximal heart rates during symptomatic ischemic attacks were in descending order, EA, ERA, RA, and VA. The maximal heart rate during ischemic attacks was significantly lower in patients with spontaneous angina than in those with exercise-induced ischemia for all types of angina (p less than 0.05, respectively). Further, the difference in maximal heart rate during ischemic attacks between the ambulatory electrocardiogram and exercise test was greater in patients with RA and VA than in those with EA. Therefore, this suggests that increased coronary vascular tone is a cause of spontaneous ischemic attacks in each type of angina pectoris.

Aged↗
PubMed1988

A case of progressive muscular dystrophy with numerous arterioluminal vessels.

A 48-year-old man had histologically demonstrated cardiac involvement associated with progressive muscular dystrophy. On coronary arteriography, numerous vascular communications between the coronary arteries and the left ventricular chamber were found. These vascular communications are considered to be the arterioluminal vessels. This is the first report of a case of progressive muscular dystrophy with numerous arterioluminal vessels.

Coronary Angiography↗