Effects of amiodarone and bepridil on ventricular depolarization and repolarization.
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Amiodarone↗
Biomedical subjects
T Osaka
Publications and source records attributed to T Osaka.
Intraperitoneal administration of recombinant human interleukin-1 beta inhibits osmotic thirst in the rat.
Decrease in water intake after intraperitoneal injection of interleukin-1 beta (IL-1 beta) was studied in the rat. Administration of IL-1 beta at a dose of 20 micrograms/kg attenuated osmotic thirst induced by intraperitoneal injection of hypertonic saline, but did not affect hypovolemic thirst induced by subcutaneous injection of either polyethylene glycol or angiotensin II. Interleukin-1 beta also decreased spontaneous intake of water but not that of 1.8% saline. The results suggest that the decrease in water intake by IL-1 beta is caused, at least in part, by suppression of osmotic thirst but not by general suppression of behavior. The effects of IL-1 beta were not secondary responses accompanied by feeding behavior, since food supply was removed during the experiments. Pretreatment with indomethacin blocked the decrease in water intake by IL-1 beta, suggesting the involvement of production of prostaglandins.
Angiotensin II↗
Structural study of cell wall mannan of a Candida albicans (serotype A) strain.
The structure of the mannan of Candida albicans NIH A-207 strain (serotype A) was investigated by adopting mild acetolysis followed by enzymolysis with an Arthrobacter GJM-1 exo-alpha-mannosidase. The resultant oligosaccharides, from pentaose to octaose (where manp = D-mannopyranose), were identified as manp beta (1----2)manp alpha (1----2)manp alpha (1----2)manp alpha (1----2)manp, manp beta (1----2)manp beta (1----2)manp alpha (1----2)manp alpha (1----2)- manp alpha (1----2)manp, manp beta (1----2)manp beta (1----2)manp beta (1----2)manp alpha (1----2)manp alpha (1----2)manp alpha (1----2)manp and manp beta (1----2)manp beta (1----2)manp beta (1----2)manp beta (1----2)manp alpha (1----2)manp alpha (1----2)manp alpha (1----2)manp, respectively. Analyses of alpha-linked oligosaccharides obtained by acetolysis under conventional conditions gave the same oligosaccharides, from biose to heptaose, as those obtained from the mannans of C. albicans NIH B-792 (serotype B) and J-1012 (serotype A, formerly serotype C).
Candida albicans↗
Excitation of hypothalamic paraventricular neurons by stimulation of the raphe nuclei.
Extracellular recordings were made from 467 anti-dromically identified neurosecretory neurons and 148 non-neurosecretory neurons in the paraventricular nucleus of the hypothalamus of hemispherectomized cats under pentobarbital anesthesia. Stimulation of the dorsal, median, and pontine raphe nuclei excited 31%, 26%, and 12% of neurosecretory neurons tested, respectively, and inhibited 9%, 7%, and 8%. The excitatory responses in 13 of 14 neurons tested were blocked by either of two intravenously administered 5-HT2 antagonists, cyproheptadine or methysergide. The 5-HT1A antagonist, (-)pindolol, partially blocked the excitatory responses elicited by raphe stimulation in three of five neurons tested. The inhibitory responses to raphe stimulation were not affected by application of these antagonists. More non-neurosecretory neurons than neurosecretory neurons were excited in response to raphe stimulation and these excitatory responses were also blocked by these antagonists. We conclude that most electrically stimulated synaptic inputs from the midbrain raphe nuclei to the hypothalamic paraventricular nucleus are excitatory and are mainly mediated by 5-HT2 receptors.
Animals↗
Inhibitory inputs to the subfornical organ from the AV3V: involvement of GABA.
Action potentials were recorded extracellularly from single neurons in the subfornical organ (SFO) of the pentobarbital-anesthetized cat following stimulation of the regions surrounding the anteroventral third ventricle (AV3V). Of 328 SFO neurons studied, 103 were antidromically activated, showing direct projections from the SFO to the AV3V. However, the major effects of stimulations of the AV3V on SFO neurons were orthodromic inhibition; almost 30% of SFO neurons were inhibited by various sites in the AV3V, while a smaller proportion of cells were excited. Local application of bicuculline, an antagonist for GABA, attenuated the inhibitory responses induced by stimulation of the AV3V in seven out of eight neurons tested. Application of GABA inhibited 16 out of 24 neurons, while that of bicuculline alone excited 11 out of 26 neurons, suggesting the tonic inhibitory action of GABA on some SFO neurons. On the other hand, application of kynurenic acid, a nonspecific antagonist for the excitatory amino acids, did not affect the excitatory responses induced by stimulation of the AV3V, but kynurenic acid itself inhibited 6 out of 18 neurons tested. Application of glutamate excited most SFO neurons. This suggests that the excitatory amino acids may be the transmitter(s) of interneurons in the SFO but may not mediate the excitation from the AV3V.
Animals↗
Developmental changes in the beta-adrenergic modulation of calcium currents in rabbit ventricular cells.
We studied the developmental changes in the beta-adrenergic modulation of L-type calcium current (ICa) in enzymatically isolated adult (AD) and newborn (NB, 1-4-day-old) rabbit ventricular cells using the whole-cell patch-clamp method. ICa was measured as the peak inward current at a test potential of +15 mV by applying a 180-450-msec pulse from a holding potential of -40 mV with Cs(+)-rich pipettes and a K(+)-free bath solution at room temperature. In control, ICa density (obtained by normalizing ICa to the cell capacitance) was significantly higher in AD cells (5.5 +/- 0.2 [mean +/- SEM] pA/pF, n = 65) than in NB cells (2.6 +/- 0.1 pA/pF, n = 60). Isoproterenol (ISO, 1 nM-30 microM) increased ICa in a dose-dependent manner for both groups. The maximal effect (Emax) of ISO, expressed as percent increase in ICa over control levels, and the concentration for one half of the maximal effect (EC50) were 203% and 51 nM, respectively, for AD cells and 111% and 81 nM, respectively, for NB cells. The effect of ISO (1 microM) on ICa was decreased as the test potential was increased from -10 to +40 mV. However, the ratio of the percent increase in ICa for AD versus NB cells was almost constant (2.09-2.45) at each test potential. Dose-response curves of forskolin (FOR, 0.3-50 microM) gave Emax and EC50 of 268% and 0.74 microM, respectively, for AD cells and 380% and 1.15 microM, respectively, for NB cells. After stimulating ICa by 10 microM ISO, the addition of 10 microM FOR produced a further increase in ICa of only 12 +/- 2% in AD cells (n = 4) but a further increase of 140 +/- 41% in NB cells (n = 6). FOR (10 microM) did not produce any increase in ICa for AD and NB cells after stimulating ICa by intracellular application of 200 microM cAMP. ICa density stimulated by 10 microM ISO (17.8 +/- 1.1 pA/pF, n = 7), 10 microM FOR (21.0 +/- 1.3 pA/pF, n = 8), or 200 microM cAMP (18.0 +/- 1.3 pA/pF, n = 5) was equivalent in AD cells, whereas ICa density stimulated by 10 microM ISO (5.8 +/- 0.6 pA/pF, n = 9) was significantly lower than that stimulated by either 10 microM FOR (13.8 +/- 1.5 pA/pF, n = 7) or 200 microM cAMP (13.4 +/- 0.7 pA/pF, n = 7) in NB cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Action Potentials↗
Spurious elevation of serum high-density lipoprotein cholesterol in patients with cholestatic liver diseases.
Strikingly discrepant values were obtained by two commercial precipitating reagents for serum HDL cholesterol determination in three patients with cholestatic liver diseases (two patients with primary biliary cirrhosis and one patient with chronic hepatitis). An abnormal alpha 2-migrating lipoprotein (slow alpha-lipoprotein) was observed in agarose gel electrophoresis for each serum. The slow alpha-lipoprotein was partly recovered in the supernatant by precipitation with polyethylene glycol, and was completely precipitated with a polyanion-containing reagent, which well explains the discrepancy. The slow alpha-lipoprotein isolated from one of the cases is notable for (1) having an intermediate particle size between normal LDL and normal HDL, (2) containing apo E as the major apolipoprotein, and (3) being enriched with cholesterol (esterified and free) and phospholipid. Cholesterol accumulation was also found in another HDL subclass, alpha 1-migrating HDL. A severe impediment in the clearance of cholesterol-loaded HDL particles from plasma was implied. Electrophoresis of serum lipoproteins and/or the measurement of serum apo E concentrations are necessary to avoid an erroneous estimation of HDL cholesterol in patients with hepatobiliary diseases.
Adult↗
Cellular mechanisms of delayed recovery of excitability in ventricular tissue.
It is well established that ventricular tissue, under some conditions, exhibits the phenomenon of postrepolarization refractoriness (PRR) in which the tissue excitability is depressed after an action potential. We have done parallel experiments on rabbit papillary muscles and on isolated rabbit ventricular cells to explain the cellular basis of this phenomenon, using elevated extracellular K+ concentration ([K+]o) (8 mM) to depolarize the tissue and the isolated cells. For isolated cells, we could separately measure cellular excitability (the inverse of the cellular current threshold) and the cellular responsiveness (the ability of the cell to generate inward current after excitation has occurred). We present two hypotheses that could explain the magnitude and time course of tissue PRR in terms of either changes in cellular excitability or changes in cellular responsiveness. We show that, although small changes in cellular excitability do occur, the predominant cellular mechanism for tissue PRR is the time course of recovery of the cellular responsiveness.
Action Potentials↗
Developmental changes in calcium currents of rabbit ventricular cells.
We investigated the postnatal development of L-type Ca2+ current (ICa) in enzymatically isolated adult (AD) and newborn (NB) (1-3-day-old) rabbit ventricular cells using the whole-cell, patch-clamp method. ICa was recorded with Cs(+)-rich pipettes and a Na(+)- and K(+)-free bath solution at 36 degrees C to eliminate other currents. ICa density (obtained by normalizing ICa to the cell capacitance) was significantly higher in AD cells than in NB cells at potential levels between 0 and +50 mV with 1.8 mM Ca2+ as the charge carrier. There was no shift in the current-voltage relation between AD and NB cells. The maximum ICa density was 9.9 +/- 2.0 pA/pF at 14 +/- 5 mV in AD cells (n = 11) compared with 5.6 +/- 2.0 pA/pF at 13 +/- 5 mV in NB cells (n = 7) (mean +/- SD). Time to half inactivation (T 1/2) showed a nearly U-shaped relation to membrane potentials from -10 to +30 mV with the shortest T 1/2 at the potential giving the maximum ICa density in both groups. T 1/2 at 0 and +10 mV was slightly but significantly longer in NB cells (16.8 +/- 4.6 and 13.5 +/- 2.4 msec, respectively) than in AD cells (12.6 +/- 3.0 and 10.6 +/0 1.5 msec).(ABSTRACT TRUNCATED AT 250 WORDS)
Calcium Channels↗
Experimental model of effects on normal tissue of injury current from ischemic region.
An ischemic myocardial region contains cells with a depolarized resting membrane potential. This depolarization leads to an intercellular current flow between the ischemic region and the surrounding normal myocardial cells, which has been termed an "injury current." We have devised an experimental model system in which an isolated rabbit ventricular cell is electrically coupled to a model depolarized cell to evaluate the effects of this injury current on the electrical properties of a normal ventricular cell. We found that the action potential duration of the isolated cell could be reversibly altered by varying the coupling resistance such that the action potential duration was shortened by high values of coupling resistance but could be considerably prolonged by lower resistance coupling. We did not observe automaticity in the isolated cell as a consequence of coupling to the depolarized model. The changes in action potential duration were accompanied by alterations in the frequency at which the isolated cell could respond to repetitive stimuli. In addition, the depolarization of the isolated cell produced by the electrical coupling led to a significant increase in the cellular excitability. This last effect may be of particular importance in understanding the mechanisms for origination of arrhythmias in the border zone of myocardial ischemia.
Action Potentials↗
[% fat of Nepali children (ranging from 6 to 18 years old) having different living style].
A comparative study of % fat was carried out on Nepali children (Ranging from 6 to 18 years old) to clarify the cause of obesity attended with modernization. 126 males and 79 females who have a natural living style, in rural district (KV) and 166 males and 133 who have a living style affected by the rapid urbanization, in suburban district (BV) were selected as subjects. %Fat was estimated from skinfold thickness according to the method of Nagamine (1975). The results summarized as follows. 1) Mean %Fat of BV in each age were clearly higher than those of KV with coincidental age, especially in male subjects. 2) According to the previous reports (Yoshimizu et al., 1990; Ito et al., 1989), it's considered physical activities in the subjects of BV were lower than those of the subjects in KV. But we could not found the nutritional factors to explain the difference of % fat between BV and KV. From these results, it's considered the difference of % fat in both districts is due to the difference of their physical activities.
Adipose Tissue↗
[Solitary ostial coronary artery stenosis in women].
Among 6,200 patients undergoing coronary arteriography using the Sones technique at the Juntendo University Hospital and the Juntendo Urayasu Hospital from 1975 to 1988, 121 patients (1.95%, 111 males and 10 females) were found to have significant (> or = 50%) stenosis in their left main trunks (LMT). Patients with systemic inflammatory disease such as syphilis or Takayasu's arteriitis, aortic valvular disease, or a history of mediastinal irradiation were excluded from this study. Stenotic lesions of the LMT were categorized into 7 types according to their locations and appearances. 1. The most common type was stenosis localized just before the branching from the left circumflex artery (42 patients or 34.7%). 2. Although the incidence of left coronary ostial stenosis was not very high (13 patients, 10.7%) as a whole, that for the female patients was the highest (30.8%) of the 7 types. Nine patients showed atherosclerotic irregularities with or without significant stenosis in the distal coronary arterial trees. Four patients, including 3 women, were diagnosed as "primary solitary ostial stenosis" of which the cause is unknown. All of the 3 women were premenopausal, and their clinical profiles were as follows: Case 1 (45-year-old): She was hospitalized because of anterior chest pain during exertion or at rest. Her electrocardiogram (ECG) showed severe ischemic ST-T changes. Coronary cineangiography disclosed a 95% stenosis in the left coronary ostium, and the distal portion of the coronary artery was normal. She had not experienced angina after her coronary artery bypass operation. Case 2 (45-year-old): She was hospitalized because of exertional chest pain.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
[An operative case of solitary interruption of the aortic arch in adult].
A 43-year-old lady was hospitalized due to easy fatiguability in the legs during exercise, and for evaluation of an abnormal shadow in the chest X-ray, and hypertension. Her blood pressure was 200/80 mmHg in the right arm, 140/70 mmHg in the left, and 110/70 mmHg in both lower extremities. Systolic vascular bruit radiating to her neck and back was audible in the Erb's area. DSA and aortogram disclosed extremely dilated vessels around the origin of the left common carotid artery. The left subclavian artery was opacified retrogradely as a subclavian blood steal via the left vertebral artery, and mild stenosis was seen at its origin. There was no evidence of associated congenital anomaly such as VSD, PDA, or ASD. The final diagnosis, solitary interruption of the aortic arch (S-IAA, type B), was made by MRI. The patient had an extra-anatomical bypass operation by using Cooley woven dacron graft from the ascending to the abdominal aorta. The result was good. S-IAA is a very rare congenital anomaly. As far as we know, only 21 patients with S-IAA including this case have been reported. A physician should be aware that a patient with S-IAA tends to have a difference of blood pressure not only between the upper and lower extremities but also between both arms, and pressure in the right arm is usually higher than that in the left. These are good signs to suspect S-IAA. And they also can be helpful to differentiate S-IAA from coarctation of the aorta.
Angiography, Digital Subtraction↗
Osmotic responses of rat paraventricular neurons by pressure ejection method.
Extracellular recordings were made from 44 spontaneously active neurosecretory and 43 unidentified neurons in the paraventricular nucleus (PVN) of the hypothalamus in urethane-anesthetized rats. Physiologically hypertonic (+30 mOsm/kg, NaCl or mannitol) and hypotonic (-30 mOsm/kg) solutions were applied by pressure through multibarrel micropipettes to the immediate vicinity of neurons. Of 44 neurosecretory neurons tested, 31 (70%) were unaffected by locally applied osmotic stimulation, and the remaining 13 were excited. Of these 31 osmotically unresponsive neurosecretory neurons, 21 were further tested with very strong hypertonic (+260 mOsm/kg, NaCl) solution, and only 7 were affected. Of 43 unidentified neurons, 28 (65%) were unaffected by osmotic stimulation, and 12 were excited. Accordingly, only parts (30%) of both the neurosecretory and unidentified neurons in the PVN were found to be osmosensitive. We concluded that some neurons in the rat PVN are osmosensitive and osmosensitivity is not specific to neurosecretory neurons in the PVN.
Action Potentials↗
Cellular mechanism of the functional refractory period in ventricular muscle.
A premature action potential elicited in ventricular muscle during the functional refractory period of a preceding action potential requires an increased stimulus intensity for successful propagation. We measured the cellular basis for these relative decreases in tissue excitability during the recovery phase by performing parallel experiments on rabbit left papillary muscle and isolated rabbit ventricular cells in addition to conducting theoretical studies with numerical simulations of action potential initiation. For each experimental preparation, the pacing protocol consisted of a train of 10 stimuli (S1) at an S1-S1 interval of 500 msec with a premature stimulus (S2) of variable S1-S2 intervals following the tenth S1 action potential. The stimulus threshold for initiation of an S2 action potential (I2) was then measured as a function of the time of occurrence of the S2 stimulus relative to the time of 95% repolarization of the tenth S1 action potential (stimulus delay [SD] time). In the tissue preparation, the I2 increased sharply for SD times less than 0 msec to a value that was 100% above the S1 stimulus threshold for SD time = -5 +/- 2.4 msec (n = 8). Similar experiments on the isolated ventricular cell showed no increases in I2 as a function of SD time but rather significant decreases in both the action potential amplitude (APA) and the maximum rate of rise of the action potential upstroke (Vmax) of the S2 action potential. The APA and Vmax for the S2 action potential were decreased to 50% of the S1 action potential values for SD time = -5.2 +/- 2.1 msec and SD time = 0.3 +/- 1.6 msec, respectively (n = 8). Both parameters reached 100% recovery by SD time = 10 msec. These results and our numerical simulations are consistent with the hypothesis that the decreases in tissue excitability that occur with premature stimulation have a cellular mechanism as a result of a decrease in cellular responsiveness (APA, Vmax) rather than an intrinsic decrease in cellular excitability.
Action Potentials↗
[A comparative study of % fat and living style on nepalese].
Measurements of %Fat, nutrient intake and maximal aerobic power (MAP) were carried out on Nepalese to clarify the cause of obesity attended with modernization. One hundred thirty-two males (KV) who have a natural living style, 20-84 years of age, in rural district and 237 males who have a living style affected by the rapid urbanization, in surburban district were selected as subjects. The subjects of surburban district were divided into two groups. One of them included 147 farmers (BF) who engage in not mechanized farming, 20-73 years of age. Another group included 90 students and wage laborers (BNF) who go to and from Kathmandu (the capital of Nepal), 20-57 years of age. %Fat was estimated from skinfold thickness according to the method of Nagamine (1975). The survey for the nutrient intake was carried out by the 24-hour recall method to obtain the individual food consumption using the food models. Measurement of MAP was made indirectly by the modified of Margaria et al (1965). The main results are summarized as follows. 1) Mean %Fat and the appearance rates of obesity in each age group showed high values in following order: BNF greater than BF greater than KV. 2) Mean caloric intake in KV was higher than those in BF and in BNF an almost all age groups and no significant difference was found between BF and BNF in all age groups. 3) No significant differences in mean fat intake and in mean animal fat intake among all groups were found in almost all age groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Variations with age and serum cholesterol level in the topographic distribution of macroscopic aortic atherosclerotic lesions as assessed by image analysis methods.
The topographic distribution of macroscopic atherosclerotic lesions in the aorta was studied by image analysis of aortas taken at autopsy from 155 males aged 10 to 54 yr. In both the thoracic and abdominal aorta, fatty streaks (FS) appear before raised lesions (RL) affecting preferential areas located longitudinally along the intercostal ostia, at the aorta bifurcation, and surrounding the points of origin of branches of the abdominal aorta. Later RL appear in the same areas of the aortic intima affected by FS at younger ages. As for the effect of serum total cholesterol (TC) in the progression of atherosclerosis, the prevalent involvement areas by FS and RL were similarly distributed as indicated by our analyses. However, areas showing frequent occurrence of FS and RL in each aortic segment were distributed more extensively at identical areas in the higher serum TC groups than in the lower TC level group. Thus, it can be concluded that FS are the precursor lesions of RL in the aorta and that the serum TC promotes the progression of atherosclerosis.
Adolescent↗
[A case of acute myocardial infarction due to coronary embolism from left atrial thrombus with atrial fibrillation].
A 55-year-old man, who has been on follow-up observation with chronic atrial fibrillation, came in with a sudden onset of chest pain on July 31, 1986. He was diagnosed as having acute myocardial infarction indicated by abnormal ECG, elevated serum enzyme and characteristic signs of echocardiography. Emergency coronary angiography was performed 2 hours after the onset of chest pain, and it was reported as showing total obstruction of the distal left anterior descending artery. Percutaneous transluminal coronary recanalization using 1,200,000 units of urokinase was unsuccessful. The repeated angiography performed 40 days later, showed normal coronary arteriogram, but left ventriculogram revealed akinesis of the apical segment. Furthermore, left atrium opacified in the levophase of pulmonary arteriogram indicated left atrial thrombus. The cause of the myocardial infarction was considered to be coronary embolism from the left atrial thrombus with atrial fibrillation. It must be the first report documented by coronary angiography, of coronary thrombo-embolism due to chronic atrial fibrillation without any underlying disease.
Angioplasty, Balloon, Coronary↗