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Biomedical subjects

Y Habuchi

Publications and source records attributed to Y Habuchi.

At least 55 records · Page 3Linked to original sources
PubMed1991

Block of Na+ channels by imipramine in guinea-pig cardiac ventricular cells.

The effects of imipramine on the Na+ current of guinea-pig ventricular myocytes were examined by the whole-cell clamp method. Imipramine inhibited the Na+ current with a dissociation constant value of 25 microM at a -130 mV holding potential. At 1 microM, imipramine caused a negative shift of the channel availability curve by 4.0 +/- 1.03 mV with its steepness unaffected. The inactivation time constants were not changed by 30 microM imipramine. Paired pulse experiments revealed that imipramine binds to the inactivated Na+ channels with time constants of 3.7 +/- 0.27 sec at -65 mV and 2.4 +/- 0.58 sec at -20 mV, and that it dissociates from the channels with time constants of 5.9 +/- 1.05 sec at -90 mV and 2.0 +/- 0.87 sec at -130 mV. From these paired pulse experiments, the dissociation constant for the interactions between imipramine and inactivated channels was calculated to be 0.67 microM, a value within its therapeutic plasma concentration. These slow interactions of imipramine with inactivated Na+ channels resulted in a slow onset of the frequency-dependent extrablock in the effects of imipramine on the Na+ current. Consequently, the imipramine-induced extrablock sufficient to terminate re-entrant tachyarrhythmias would not develop shortly after their initiation. Short depolarizations of 1- to 3-msec duration sustained appreciable extra blockage when a high concentration of 10 microM imipramine was used, or they were repeatedly applied at a high frequency. However, access of imipramine to the open channels seems to play a minor role in the drug-channel interactions.

Action Potentials↗
PubMed1991

[A case of central retinal vein occlusion accompanied by central retinal artery occlusion].

A 81-year-old woman developed central retinal vein occlusion (CRVO) in her left eye subsequent to central retinal artery occlusion (CRAO). She noticed sudden visual loss in the left eye. At initial examination, her left visual acuity was 0.03, and only a small visual field was preserved at temporal area. The left fundus showed findings of mild non-ischemic CRVO. In addition white clouded retina was recognized at the left posterior pole which indicated CRAO. FAG showed remarkably prolonged arterial circulation, but no retinal capillary obliteration. Then retinal hemorrhage increased rapidly and her left eye developed hemorrhagic retinopathy. Two weeks after initial examination, FAG showed extensive retinal capillary obliteration. In this case it was supposed that central retinal artery occlusion due to arteriosclerosis produced ischemic capillaropathy and venous thrombosis, after which restoration of arterial circulation caused hemorrhagic retinopathy.

Aged↗
PubMed1990

Anticholinergic action of quinidine sulfate in the rabbit atrioventricular node.

Anticholinergic action of quinidine sulfate was electrophysiologically studied by recording spontaneous action potentials and membrane current of the rabbit atrioventricular node. In the presence of 0.1 mumol/l carbachol, the spontaneous activity of the atrioventricular nodal preparations was markedly inhibited, whereas subsequent addition of 1, 5 and 20 mumol/l quinidine restored automaticity in a concentration-dependent manner. In some preparations, quinidine at concentrations of 5 mumol/l and higher slowed the spontaneous activity by its direct membrane action even in the presence of carbachol. The dose-response curve for acetylcholine action on the spontaneous firing frequency showed that one molecule of acetylcholine bound to one muscarinic receptor of the atrioventricular node cell (Hill coefficient = 1.2). A parallel shift of this curve towards higher acetylcholine concentrations was observed at 0.03, 0.1 and 0.3 mumol/l but not at 1 and 3 mumol/l quinidine, suggesting a noncompetitive antagonism of quinidine against acetylcholine. Voltage clamp experiments revealed that 5 mumol/l quinidine reduced the slow inward current, hyperpolarization-activated inward current, and delayed rectifying K+ current, through its membrane actions. Quinidine at this concentration almost completely suppressed the acetylcholine-activated K+ current, which showed a relaxation phenomenon. Hence, the direct blockage of the acetylcholine-activated K+ current by quinidine was considered responsible for the anticholinergic action of this drug. We conclude that quinidine is a non-specific ionic channel blocker that inhibits all the membrane currents in the atrioventricular node including the acetylcholine-activated K+ current.

Action Potentials↗
PubMed1990

Electrophysiologic actions of aprindine in rabbit atrioventricular node.

Aprindine hydrochloride is a potent antiarrhythmic agent against various atrial and ventricular tachyarrhythmias. To elucidate its pharmacological actions in the atrioventricular node, electrophysiologic experiments were conducted by applying microelectrode and voltage clamp methods to small preparations of the rabbit atrioventricular node. At a concentration 1 mumol/l, aprindine decreased the spontaneous firing frequency, maximal rate of depolarization, action potential amplitude, and take-off potential (P less than 0.05, n = 7). The spontaneous and rate-controlled action potential durations at 50 and 100% repolarization were prolonged by aprindine. Voltage-clamp experiments using the double microelectrode method revealed that aprindine blocked the slow inward current (Isi) in a voltage-dependent manner with a dissociation constant of 10 mumol/l and Hill coefficient of 0.8. The steady-state inactivation curve for Isi was shifted toward more negative potentials by 2.5 +/- 0.9 mV (P less than 0.05, n = 5) without a significant change in the slope factor. This finding suggests that aprindine has a higher affinity for inactivated slow inward (or Ca2+) channels than for resting channels. Aprindine caused use-dependent block of Isi, a result consistent with the drug's slow dissociation from inactivated Ca2+ channels. The delayed rectifying K+ current (IK) tail obtained on repolarization from +10 mV to -60 mV was significantly decreased from 15.4 +/- 2.4 to 6.8 +/- 1.4 nA (P less than 0.01, n = 6) and the deactivation time constant significantly increased by 20.7% (P less than 0.01, n = 6). The steady-state activation curve for IK was shifted in the hyperpolarized direction by 6.9 +/- 2.9 mV, suggesting a potent voltage-dependent block of this current by aprindine. The hyperpolarization-activated inward current (Ih) was decreased from 14.4 +/- 5.4 to 12.0 +/- 5.5 nA (P less than 0.05, n = 5). The transient outward and inward currents induced by 1 mumol/l acetylstrophanthidin were almost completely suppressed after the addition of 1 mumol/l aprindine. These results suggest that aprindine exerts a negative chronotropic action both by slowing deactivation of IK and by reducing Isi and Ih, and delays atrioventricular nodal conduction by reducing Isi and IK. These blocking actions of aprindine together with its inhibition of the transient outward and inward currents may explain its antiarrhythmic effects on the atrioventricular node.

Action Potentials↗
PubMed1990

Recovery of the slow inward current from Ca2(+)-mediated and voltage-dependent inactivation in the rabbit sinoatrial node.

The process of recovery from inactivation of the slow inward current (isi) in the rabbit sinoatrial (S-A) node was evaluated by voltage clamp experiments using double microelectrode method. Double pulse experiments were carried out on preparations loaded with Cs+ using nystatin. The rate of the rapid isi inactivation depended on the amplitude of isi rather than the membrane potential. After a 50 ms depolarizing prepulse isi rapidly recovered from inactivation at -40 mV with a time constant of 84 +/- 25 ms, whereas after a longer prepulse, an additional slow recovery phase with a time constant of 1 to 2 s was observed. The amount of isi during the fast recovery phase following a 300 ms prepulse to -20 mV was smaller than that following a prepulse to +20 mV, as predicted by a Ca2(+)-mediated inactivation mechanism. Conversely, a prepulse to +20 mV caused a greater inactivation in the slow recovery phase, suggesting a voltage-dependent mechanism. The inactivation curve obtained during the fast recovery phase using 50 ms prepulses was U-shaped, indicating a predominant role of the Ca2(+)-mediated mechanism, whereas that obtained during the slow recovery phase resembled previously reported voltage-dependent steady state inactivation (f infinity) curve. These results indicate that the fast and slow phases of recovery represent the removal of Ca2(+)-mediated and voltage-dependent isi inactivation, respectively. The presence of Ca2(+)-mediated inactivation via steady state Ca2+ inflows was also suggested.

Animals↗
PubMed1989

Thyroid carcinoma in solitary hot thyroid lesions on Tc-99m sodium pertechnetate scans.

Sixteen patients with nonsuppressible solitary hot thyroid lesions (SHTL) identified on T3 suppression images using Tc-99m sodium pertechnetate were studied over a period of 5 years. Of the 16 patients, 7 (44%) had papillary adenocarcinoma (PAC) and 9 (56%) had follicular adenoma (FA). Of the 7 patients with PAC, 3 were toxic and 4 nontoxic. Of the 9 patients with FA, 2 were toxic and 7 nontoxic. The Tl-201 chloride thyroid scans were useful in locating SHTL and revealing extranodular thyroid tissue. The echography was sensitive to visualization of the nodule structures. However, there were no significant differences between the clinical findings, radionuclide images, and echograms between for PAC and FA. All patients with PAC were treated by partial thyroidectomy and there were neither regional nor distant metastasis in any of them. In conclusion, our study provided the following extremely interesting result: SHTL in the present series have a higher incidence of malignancy than previously reported autonomously functioning thyroid lesions (AFTL). Histological examination is necessary for the diagnosis and management of SHTL and surgical treatment should be considered.

Adenocarcinoma, Papillary↗
PubMed1989

Time- and voltage-dependent block of the delayed K+ current by quinidine in rabbit sinoatrial and atrioventricular nodes.

The modes in which quinidine blocks the delayed K+ current (IK) of rabbit sinoatrial and atrioventricular nodes were investigated by voltage clamp experiments using small preparations. Depolarizing pulses were applied from a holding potential of -50 mV and resultant IK current was evaluated. At a concentration of 2 x 10(-6) M, quinidine blocked 52 +/- 5% of IK with a 1000-msec test pulse of 0 mV, whereas it inhibited the slow inward current by only 5 to 10%. IK inhibition was enhanced with increasingly larger depolarizations. The activation curve obtained with the use of 1000-msec test pulses shifted toward hyperpolarization by 3.0 mV and its slope factor increased from 7.3 to 8.8, suggesting a voltage-dependent mechanism for IK blockage. Short and small depolarizing pulses from the holding potential of -50 mV hardly affected II. The activation of IK in the presence of quinidine did not show any delay. These results indicated a low affinity of quinidine to the closed (deactivated) channels. The deactivation time constant of IK was significantly prolonged from 120 to 145 msec at -50 mV. By applying the modulated receptor model to the K+ current, the tail current in the presence of quinidine was well reconstructed when the time constant of drug-channel interactions was 300 msec at -50 mV and 2000 msec at -30 mV. It is suggested that the unblocking of quinidine slows the decay of the IK tail current.

Animals↗
PubMed1988

The development of a solitary toxic thyroid nodule following Graves' disease.

A 52-year-old woman developed a toxic, solitary, autonomously functioning thyroid nodule four years after antithyroid drug treatment for Graves' disease. When she was initially seen, a thyroid scan showed the homogeneous enlargement of both lobes with increased uptake. Graves' disease was diagnosed and the patient was treated with methimazole. Thyroid function was well-controlled with medication for 18 months, after which the patient stopped taking the drug for three years. Four years after Graves' disease was diagnosed, the patient again showed symptoms of hyperthyroidism. The etiology was a toxic, autonomously functioning nodule.

Female↗
PubMed1988

Ionic basis of depressed automaticity and conduction by acetylcholine in rabbit AV node.

To investigate the ionic mechanisms underlying the negative chrono- and dromotropic effects of acetylcholine (ACh) on the atrioventricular (AV) node, experiments were carried out in rabbit AV node preparations with the use of double-microelectrode techniques. In current-clamp experiments (n = 6), 10(-6) M ACh hyperpolarized the resting membrane from -42.3 to -58.2 mV, decreased the specific membrane resistance from 2.54 to 1.27 k omega.cm2, decreased the space constant from 556 to 384 microns, and reduced the membrane time constant from 23.0 to 12.4 ms. Under voltage-clamp conditions, 10(-6) M ACh decreased the slow inward current by 11% and activated an ACh-sensitive outward K+ current (IACh). IACh possessed an inward rectifying property and exhibited a relaxation phenomenon with a time constant of 60-100 ms at a membrane potential of 0 to -80 mV. Its reversal potential varied with a slope factor of 56 mV per 10-fold increase in external K+ concentration. These results suggest that 1) IACh is selective for K+, 2) IACh inhibits phase 4 and phase 0 depolarizations and reduces the space constant for electronic current spread in the AV node, and 3) the negative chrono- and dromotropic actions caused by IACh may be augmented by the ACh-induced reduction in the slow inward current.

Acetylcholine↗
PubMed1988

Pulmonary hypertension in a patient with rheumatoid arthritis.

A 53-year-old woman who had suffered from severe rheumatoid arthritis developed pulmonary hypertension. Her small arteries in the lung showed plexogenic arteriopathy with fibrous intimal hyperplasia. There was also vasculitis of the small arteries in other organs and mural thrombosis in the pulmonary stem and abdominal aorta. The plexogenic arteriopathy which was responsible for pulmonary hypertension appears to be the result of vasculitis in association with rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed1988

Membrane actions of quinidine sulfate in the rabbit atrioventricular node studied by voltage clamp method.

The effects of quinidine (0.01-20 micrograms/ml) on spontaneous action potentials and membrane current systems of the rabbit atrioventricular node were studied. At therapeutic concentrations, this drug decreased the action potential amplitude, the maximal diastolic potential, the threshold potential as well as the maximal rate of depolarization and showed a negative chronotropic action. Quinidine, at 5 micrograms/ml, decreased the peak slow inward current by 30.2%, increased its time constant of inactivation by 27.3%, shifted the steady-state inactivation curve toward more negative membrane potentials by 2.8 mV and decreased its fully activated current. Quinidine exerted not only resting but also use-dependent blocking actions on the slow inward current. The depression of the action potential upstroke can thus be explained by the reduction in this current. The outward K+ tail current was decreased by 65.4% and its deactivation time constant was increased by 19.0%. These effects may have contributed to the prolongation of the action potential duration, the reduction in the maximal diastolic potential and the slowing of diastolic depolarization. Quinidine shifted the steady-state activation curve for this K+ current toward hyperpolarization by as much as 7.8 mV. It decreased the hyperpolarization-activated inward current by 16.3% and increased its activation time constant by 10.1%, but this current appeared to play a small role in reducing the rate of diastolic depolarization. These observations indicate that, depending upon dose, quinidine has the potential to decrease all of the time- and voltage-dependent ionic currents in atrioventricular nodal cells.

Action Potentials↗
PubMed1987

Electrophysiologic effects of nicorandil, a new antianginal agent, on action potentials and membrane currents of rabbit atrioventricular node.

Electrophysiologic effects of nicorandil, a newly developed coronary vasodilator, on the atrioventricular (AV) node were studied using space-clamped small preparations of the rabbit AV node. At the concentrations of 10(-6), 10(-5) and 10(-4) mol/l, this drug did not cause significant changes in the action potential characteristics including the spontaneous firing frequency, overshoot, maximum diastolic potential, maximum rate of depolarization and action potential duration. When the resting membrane potential of the AV node was obtained by a superfusion with verapamil and then nicorandil was added to the perfusate, no hyperpolarization was observed. This was in sharp contrast to the reported hyperpolarizing action of this drug on the atrial muscle, Purkinje fibres and vascular smooth muscle where the resting potential is much more negative. On the other hand, voltage clamp experiments using double microelectrode techniques revealed that 10(-5) to 10(-4) mol/l nicorandil increased the steady-state outward current at potentials positive to -40 mV and the steady-state inward current at potentials negative to -40 mV. Such a nicorandil-sensitive component of the steady-state current had an average reversal potential of -41.8 mV (n = 5). This component was considered to reflect changes in the time-independent background current, although, at more negative potential levels, it may partially reflect an increase in the hyperpolarization activated inward current (ih). Nicorandil, at the concentrations of 10(-5) and 10(-4) mol/l, increased the slow inward current (isi) by 10.8% (n = 5, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1987

Three-dimensional vectorcardiography (3-D VCG) by computer graphics in old myocardial infarction.

By using computer graphics we rotated the vector loop and three coordinate axes to find the viewpoint where the infarctional changes are maximally exposed and demonstrated the advantage of the "3-D VCG" over the conventional VCG by defining the quantitative "MI index." The orthogonal electrocardiogram recorded by the Frank lead system was digitally measured and processed by a microcomputer. The loops and axes were rotated about the X axis (X-rot) and the Y axis (Y-rot). The spatial vector loop and orthogonal coordinates can be presented as viewed from any spheric direction. Eight quadrants were illustrated with four colors and red circles. The subjects consisted of 30 patients with old anterior myocardial infarction (MI) and 15 patients with old inferior MI. We measured the area of "Bite" in anterior MI and superior displacement in inferior MI. The MI index was defined and averaged in 361 directions. In anterior MI, the maximum mean index was obtained when X-rot is +90 degrees and Y-rot -40 degrees, viewed from upward and leftward, whereas in inferior MI it was obtained when X-rot is -50 degrees and Y-rot -80 degrees, viewed from downward and leftward. These values were significantly higher than those in conventional VCG projections, substantiating superior diagnostic sensitivity of 3-D VCG.

Adult↗
PubMed1986

A follow-up study using iodine-131 metaiodobenzylguanidine imaging in a patient with neuroblastoma.

A new radiopharmaceutical, I-131 metaiodobenzylguanidine (I-131 MIBG) was used to determine the location and to follow-up tumors in a 13-month-old girl with neuroblastoma. I-131 MIBG imaging revealed both a primary abdominal tumor and a distant metastatic orbital tumor. Follow-up study with I-131 MIBG imaging demonstrated significant resolution of tumors after external radiotherapy and chemotherapy. I-131 MIBG imaging is a simple, safe, and specific method of determining the location of tumors and also is clinically useful in the evaluation and management of patients with neuroblastoma.

3-Iodobenzylguanidine↗