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T Shirayama

Publications and source records attributed to T Shirayama.

At least 37 records · Page 2Linked to original sources
PubMed1993

Carbachol-induced sodium current in guinea pig ventricular myocytes is not regulated by guanine nucleotides.

Muscarinic (M2) receptor occupancy by carbachol induces a tetrodotoxin- and pertussis toxin-resistant Na+ current which underlies its positive inotropic effect in guinea pig ventricular cells. We tested the effect of activating [GTP gamma S, Gpp(NH)p] and inactivating (GDP beta S) guanine nucleotides on this carbachol-induced current because guanine nucleotide binding proteins are reported to transduce the effect of muscarinic agonist. A whole-cell voltage clamp method was used. The carbachol (300 microM)-induced current was not significantly changed at any membrane voltage in the absence and the presence of 10 microM GTP gamma S, 100 microM Gpp(NH)p or 500 microM GDP beta S in the patch pipette (inward current amplitude at -80 mV: -21 +/- 1.5 pA, control; -22 +/- 1.3 pA, GTP gamma S; -20, -16 pA, Gpp(NH)p; -20 +/- 2.3 pA, GDP beta S; n = 31, 11, 2 and 14, respectively). The current amplitude was not affected by prolonged dialysis (120 min) of the cell with Gpp(NH)p and/or by the presence of greater concentrations of guanine nucleotides. On the other hand, 10 microM GTP gamma S directly activated the muscarinic K+ channel current within 60 sec after patch rupture in atrial myocytes; either GTP gamma S or GDP beta S (500 microM) occluded activation of this current by carbachol. When isoproterenol had increased L-type Ca++ current in ventricular myocytes, carbachol-induced inhibition of this current was suppressed when GTP gamma S (10 microM) was present in the pipette solution. Therefore, myocytes were dialyzed with effective concentrations of guanine nucleotides.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Slow kinetic property of mexiletine in guinea pig atrium.

We studied the onset and offset of use-dependent block (UDB) of maximum rate of rise of action potential (Vmax) with 3 x 10(-5)M mexilietine in guinea pig left atrium. A large decrease of Vmax was observed between the first and the second excitation when the preparations were stimulated at 4Hz after two minutes of rest period. UDB after the second excitation developed slowly to reach steady state within 30 sec. These two onset rates were 1.016 +/- 0.055 and 0.070 +/- 0.009/action potential. Recovery process was also fitted with two exponential equations. The time constant of the fast recovery was 528 +/- 23 msec. and the slow one was 3099 +/- 435 msec. The relative contribution of the slow component was 38.3 +/- 2.6% in the onset and 29.7 +/- 3.1% in the recovery. In spite of elevated maximum diastolic potential at 4 Hz stimulation, the relationship between resting membrane potential and Vmax disclosed voltage-dependent block of Vmax was no more than 5%. It is concluded that mexiletine has a slow kinetic component as well as a fast one. When atrial muscle is depolarized, Vmax decreases further. Therefore, mexiletine may be more effective against the atrial arrhythmias than predicted previously.

Action Potentials↗
PubMed1992

[Electrophysiologic effects of flecainide on guinea pig atrium].

We investigated the effects of flecainide on guinea pig atrial muscle. Using Langendorff's method, the whole heart of a guinea pig was perfused with Tyrode's solution containing acetylcholine (3 x 10(-7) M). Then, with right atrial extrastimulus and high frequency pacing method, the following values were measured before and after administration of flecainide (10(-7)-10(-5) M). A) Effective refractory period (ERP); the longest coupling interval which failed to produce right atrial activity at premature stimulus. B) Interatrial conduction time (ACT); After right atrial stimuli by trains at PCL 200 ms for 5 min the interval from the stimulation to the first deflection of the left atrial activity. C) Atrial fibrillation threshold (AFT); the minimal amount of current required to induce atrial fibrillation lasting for more than 30 sec by 50 Hz high frequency stimulation. Flecainide lengthened ERP (> or = 3 x 10(-5) M) and ACT (> or = 10(-7) M). Flecainide (10(-5) M) significantly increased AFT which correlated well with ERP (r = 0.81, p < 0.002) and ACT (r = 0.84, p < 0.002). In conclusion these effects of flecainide on guinea pig atrium might explain in part the clinical effectiveness of the drug on paroxysmal atrial fibrillation.

Animals↗
PubMed1991

Prolonged atrial activity due to delayed conduction in the atrium of patients with paroxysmal atrial fibrillation.

We investigated the relationship between the duration of electrical atrial activity and intra-atrial conduction time to determine whether the prolonged atrial activity was due to delayed conduction in the human atrium. The study included 15 patients with paroxysmal atrial fibrillation (PAF) and 15 control patients. The duration of atrial electrical activity was measured by selecting a minimum electrographic amplitude of 50 microV. In patients with PAF, the duration of atrial activity was prolonged in proportion to the delay of interatrial conduction time from the high right atrium to the coronary sinus as the coupling interval of premature extrastimuli was decreased. Both the fragmented atrial activity zone and the interatrial conduction delay zone were wider in patients with PAF than in control patients. It is concluded that assessment of the duration of atrial activity with a minimum amplitude of 50 microV is useful in evaluating human atrial vulnerability since it reflects the atrial conduction delay in patients with PAF.

Adolescent↗
PubMed1991

Inositol trisphosphate promotes Na-Ca exchange current by releasing calcium from sarcoplasmic reticulum in cardiac myocytes.

An early inward tail current evoked by membrane depolarization (from -80 to -40 mV) sufficient to activate sodium but not calcium current was studied in single voltage-clamped ventricular myocytes isolated from guinea pig hearts. Like forward-mode Na-Ca exchange, this early inward tail current required [Na+]o and [Ca2+]i and is thought to follow earlier reverse-mode Na-Ca exchange that triggers Ca2+ release from sarcoplasmic reticulum. The dependence of the early inward tail current on [Ca2+]i was supported by the ability of small (+10 mV) and large (+80 mV) voltage jumps from -40 mV to decrease and increase, respectively, the size of early inward tail currents evoked by subsequent voltage steps from -80 to -40 mV. As expected, tetrodotoxin selectively inhibited the early inward tail current but not the late inward tail current that followed voltage jumps to +40 mV test potentials. Although tetrodotoxin also blocked the fast Na+ current, replacement of extracellular Na+ by Li+ sustained the fast Na+ current. However, Li+, which does not support Na-Ca exchange, reversibly suppressed both the early and late inward tail currents. Inhibitors (ryanodine and caffeine) and promoters (intracellularly dialyzed inositol 1,4,5-trisphosphate) of sarcoplasmic reticulum Ca2+ release decreased and increased, respectively, the magnitude of the early inward tail current. The results substantiate the hypothesis that Ca2+ release from the sarcoplasmic reticulum participates in early Na-Ca exchange current and demonstrate that inositol 1,4,5-trisphosphate, by releasing Ca2+ from the sarcoplasmic reticulum, can promote Na-Ca exchange across the plasma membrane.

Animals↗
PubMed1991

Electrophysiological effects of sodium channel blockers on guinea pig left atrium.

The electrophysiological effects of five sodium channel blockers (mexiletine, lidocaine, disopyramide, aprindine and flecainide) on the guinea pig left atrium were investigated by recording the action potential and its maximum rate of rise (Vmax). The onset and offset kinetics of use-dependent block of Vmax were analyzed. Lidocaine, aprindine and flecainide were classified clearly as fast, intermediate and slow, respectively. Mexiletine and disopyramide had two components in onset and offset of use-dependent block. Mexiletine showed fast and intermediate kinetics, whereas disopyramide showed intermediate and slow kinetics. Action potential duration at 90% repolarization (APD) was prolonged by disopyramide and mexiletine. The other drugs did not change the action potential duration. Effective refractory period was prolonged by all drugs with relative potency in the following order: disopyramide greater than mexiletine greater than lidocaine greater than aprindine = flecainide. In conclusion, the modes of actions of sodium channel blockers on the atrium were disclosed to be different from those on the ventricle. The pharmacological therapy for atrial arrhythmias should be based on the electrophysiological effects of the drugs on the atrium, not on the ventricle.

Action Potentials↗
PubMed1991

[Electrophysiological effect of verapamil on human atrium].

To investigate the effect of verapamil on atrial vulnerability, the following measurements were performed before and after the intravenous administration of verapamil (0.15 mg/kg) in 10 subjects with paroxysmal atrial fibrillation (Paf), and 10 subjects without Paf (non-Paf). During the sinus rhythm, 1) intra-/interatrial conduction time (Intra-/Inter- ACT); the initial deflection of high right atrium (HRA) to that of His bundel/coronary sinus were measured. After 8 consecutive HRA stimuli (A1), premature stimulus (A2) was introduced by shortening the coupling interval (A1A2) and we measured 2) conduction delay zone (CDZ); the zone of A1A2 with the prolongation of Inter-ACT, 3) % maximum atrial fragmentation (%MAF); % maximum value of the ratio of HRA activity width at A2 (Awt) against that at A1 (Awc), 4) fragmented atrial activity zone (FAZ); the zone of A1A2 with % value of Awt/Awc more than 150%,5) repetitive atrial response (RAR); more than 2 atrial activities which occur in response to A2. (6) right atrial effective refractory period (RAERP). Verapamil significantly shortened CDZ and %MFA, slightly lengthened RAERP, and had RAR disappear in Paf, while it did not effect any indices significantly in non-Paf. We concluded that verapamil could reduce atrial vulnerability in Paf due to blocking of atrial conduction delay mediated by slow response fibers.

Adolescent↗
PubMed1990

Effect of diltiazem on spontaneous cyclic Ca2+ release from sarcoplasmic reticulum.

We used saponin-treated skinned fibers isolated from papillary muscles of the right ventricle of guinea pigs to compare the effects of diltiazem on the spontaneous cyclic Ca2+ release from the sarcoplasmic reticulum (SR) of cardiac muscle with the effects of caffeine. Both diltiazem and caffeine increased the frequency of cyclic contractions in EGTA (ethyleneglycol-bis-(beta-aminoethylether) N,N,N',N'-tetra-acetate)-free solution and induced an incomplete, concentration-dependent relaxation of the muscle. The results suggest that the spectrum of the pharmacological effects of diltiazem on the SR is similar to that for caffeine, that is diltiazem accelerates the spontaneous Ca2+ release from the SR and suppresses Ca2+ reuptake by the SR, and that diltiazem as well as caffeine may act on the SR in vivo in a specific condition.

Animals↗
PubMed1990

The effects of an extra-stimulation on post-extra-systolic potentiation in papillary muscle of rats.

The mechanism of post-extrasystolic potentiation (PESP) is unclear. It has previously been suggested that changes in both the calcium release from the sarcoplasmic reticulum (SR) and the transsarcolemmal calcium influx are factors in the development of PESP in guinea-pigs. This experiment investigated the effects of a resting interval and a coupling interval on PESP in rat papillary muscles, which have a well-developed SR. An extra-stimulation was induced at various coupling intervals and a variety of post-extrasystolic intervals were set. The PESP was not dependent on the coupling interval. The post-extrasystolic interval at which the maximal % PESP was obtained was about 90 sec, and post-extrasystolic interval-% potentiation of the PESP relationship curve consisted of an ascending limb and a descending limb. Caffeine eliminated the PESP in a concentration-dependent manner. These findings suggest that SR calcium release plays an important role in the mechanism of PESP in rats. This is consistent with results from guinea-pigs, and implies that the calcium capacity and/or retention of the SR may characterize the post-extrasystolic interval-% PESP relationship in muscle from different species.

Action Potentials↗
PubMed1990

[Electrophysiological effects of flecainide acetate on guinea-pig left atrial cells].

Using conventional glass microelectrode technique, electrophysiological effects of flecainide acetate on guinea-pig left atrial muscle fibers were examined. Resting membrane potential was not affected by flecainide at any concentrations tested (10(-7) M-3 X 10(-5) M), although overshoot potential was significantly decreased at the concentration over 3 X 10(-6) M. Effective refractory period significantly increased at 10(-5) M. The reduction of Vmax was about 25% and 50% by 3 X 10(-6) M and 10(-5) M, respectively at 1 Hz. At 3 X 10(-6) M, Vmax decreased by about 10%, 15%, 22%, 33%, and 34% at 0.2, 0.5, 1, 2, and 3 Hz respectively. Flecainide, decreased Vmax of atrial muscle fibers in a dose and frequency dependent manner. It is suggested that flecainide might be effective in the treatment of atrial tachyarrhythmias.

Action Potentials↗
PubMed1990

[Elucidation of reversibility in myocardial injury during hypoxia and reoxygenation in papillary muscles of rats].

We reported the calcium release of sarcoplasmic reticulum (SR) is the major source of activator calcium to postrest contraction (PRC), and that the transsarcolemmal calcium influx is (the major source of activator calcium) to regular contraction in rats. In this study we investigated the combined effects of hypoxia and glucose elimination on PRC and regular contraction. In other words, using papillary muscles of rats, to elucidate the characteristics of reversible or irreversible myocardial injury after ischemia, we investigated the effects of hypoxia on both SR and sarcolemmal functions. After 90 min hypoxia (the first hypoxia-90 min), regular contraction was significantly more reduced than PRC (p less than 0.001; n = 16). With 90 min of reoxygenation, the recovery from hypoxic injury of PRC was better than recovery from injury of regular contraction (p less than 0.01; n = 16). After either 30 min hypoxia (the second hypoxia-30 min) or 60 min hypoxia (the second hypoxia-60 min), regular contraction was also more reduced than PRC, respectively (p less than 0.001; n = 8). However, the recovery from both the second hypoxic injury-30 min and the second hypoxic injury-60 min of PRC was not significantly different from that of regular contraction, respectively (NS; n = 8). Percentages of diastolic tension, which were normalized by baseline regular contraction, increased during hypoxia and decreased incompletely after reoxygenation. After the first reoxygenation of 90 min, 1 microM noradrenaline significantly augmented the magnitude of regular contraction (p less than 0.05; n = 5).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1990

[Different sensitivity of sinus node and atrioventricular node to adenosine triphosphate].

We showed that higher concentration of adenosine 5'-triphosphate (ATP) was required to prolong the spontaneous cycle length of the sinus node (SN) than that required to prolong the spontaneous cycle length of the atrioventricular node (AVN). Spontaneously beating preparations of SN and AVN of rabbit (n = 8) were superfused with Tyrode solution containing 10(-8)-10(-3)M ATP, and action potential was recorded. The negative chronotropic action of ATP was dependent on the concentration. The required concentration of ATP to prolong spontaneous cycle length significantly (p less than 0.01) was 10(-5)M in SN and 10(-6)M in AVN, respectively. At concentrations higher than 10(-6)M, the degree of prolongation was greater in AVN than in SN (p less than 0.01). 10(-7)M dipyridamole enhanced this effect of ATP, while 10(-4)M theophylline reduced it. Action potential duration of 50% repolarization was not changed significantly in either SN or AVN at concentrations up to 10(-3)M. Maximum diastolic potential (MDP) was hyperpolarized from 10(-8)M to 10(-4) M. Hyperpolarization of MDP induced by ATP was greater in AVN than in SN but it was not statistically significant. MDP was depolarized by 10(-3) M ATP in both SN and AVN. The maximum velocity of depolarization was slightly larger in both SN and AVN as the concentration of ATP was increased in the perfusate. However, it was not statistically significant. 10(-3) M ATP decreased the maximum velocity of depolarization.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1989

Effect of paced cycle length on sinus node effective refractory period before and after autonomic blockade in patients with sick sinus syndrome.

Effect of basic paced cycle length on sinus node effective refractory period was studied in 22 patients with sick sinus syndrome. Sinus node effective refractory period was measured using three different paced cycle lengths before and after pharmacologic autonomic blockade. Sinus node effective refractory period could be measured at one cycle length, at least, in 59% of the patients before blockade, however, it could be measured at two or more cycle lengths in only 18% of patients because of the chaotic response of sinus node against premature stimuli. It could be measured after pharmacologic autonomic blockade in 68% of the patients at two or more paced cycle lengths. On the other hand, the rest of the patients showed no measurable sinus node effective refractory period at any cycle length, for their sinus node effective refractory periods were shorter than their right atrial effective refractory periods. The comparison of sinus node effective refractory period at different paced cycle lengths was unsuccessful before pharmacologic autonomic blockade, while the refractory period was significantly prolonged as cycle length was shortened after blockade. We concluded that (1) sinus node effective refractory period in humans is prolonged as paced cycle length decreases, (2) the autonomic reflex is the major disturbing factor in measuring sinus node effective refractory period, and pharmacologic autonomic blockade can be usefully employed to eliminate a chaotic sinus nodal response, (3) when sinus node effective refractory period is shorter than right atrial effective refractory period, a shorter paced cycle length should be used for definite measurement of the former.

Adolescent↗
PubMed1989

[Evaluation of right ventricular systolic and diastolic properties using 81mKr scintigraphy with continuous infusion].

To evaluate right ventricular (RV) systolic and diastolic properties in patients with various heart diseases, RV volume curves obtained from 81mKr scintigraphy with continuous infusion were analyzed. The data were acquired in right anterior oblique position for five minutes, and from RV time activity curve and its first derivative curve, ejection fraction and peak ejection rate as systolic indices, and peak filling rate, time to peak filling and 1/3 mean normalized diastolic filling rate as diastolic indices were calculated. Ejection fraction in patients with dilated cardiomyopathy was lower than that in controls, but there was no difference in systolic indices among controls and patients with the other heart diseases. However, diastolic indices in patients with hypertrophic cardiomyopathy, patients with hypertensive heart disease, patients with dilated cardiomyopathy, patients with inferior myocardial infarction, and some patients with anteroseptal myocardial infarction were lower than those in controls. In conclusion, analysis of RV time activity curve by 81mKr scintigraphy with continuous infusion provides RV systolic and diastolic indices, which may permit evaluation of RV systolic and diastolic properties in various heart diseases.

Female↗
PubMed1989

[Effect of mexiletine on human atrial vulnerability].

The effect of mexiletine on human atrial vulnerability was investigated in 14 subjects (8 with paroxysmal atrial fibrillation, 2 with paroxysmal atrial tachycardia, 2 with ventricular tachycardia, 1 with sick sinus syndrome and 1 with Wolff-Parkinson-White syndrome). During the electrophysiologic study, after 8 consecutive stimuli (A1) were delivered through the electrode catheter positioned at high right atrium, premature stimulus (A2) was introduced, and following measurements were made; 1) Aw: atrial activity width of A1, 2) maximum atrial fragmentation (MAF): the longest atrial activity width of A2, which was expressed by the relative value against Aw, 3) fragmented atrial activity zone (FAZ): the zone of the coupling interval (A1A2) with the prolongation of the atrial activity width at A2 more than 150% against Aw, 4) conduction delay zone (CDZ): the zone of A1A2 with the prolongation more than 20 msec of the intraatrial conduction time at A2 from high right atrium to coronary sinus or low right atrium against the intraatrial conduction time at A1, and 5) right atrial effective refractory period (RAERP). These measurements were repeated after the intravenous administration of mexiletine (2 mg/kg/10 min). 3 cases (case 12, 13 and 14), whose FAZ and CDZ were 0 msec, were excluded from the following evaluation. Mexiletine showed little effect on Aw and RAERP, but significantly shortened MAF and FAZ (p less than 0.001 and p less than 0.05, respectively). CDZ were also reduced in 3 cases and remained unchanged in 6 cases, though no statistical difference of CDZ was recognized between before and after the administration of mexiletine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Swallowing-induced arrhythmia.

Deglutition tachyarrhythmia, first reported in 1926 by Sakai and Mori, is a rare clinical entity. Vagal reflex has been supposed to be responsible for the induction of the arrhythmia. We have recently studied a patient with swallowing-induced premature atrial contractions. Atropine sulfate and catecholamine infusion increased the frequency of the arrhythmia, while beta blockade suppressed it. It is suggested that the mechanism of the swallowing-induced arrhythmia might be related to a sympathetic reflex. As far as we know, there have been few reports in which the sympathetic reflex was proposed to be responsible for the arrhythmia.

Adult↗
PubMed1988

A case of left ventricular aneurysm of uncertain etiology presenting as ventricular tachycardia.

A case of a 59-year-old Asian male with several episodes of syncope and palpitation is reported. Electrophysiologic study disclosed that sustained ventricular tachycardia was induced by programmed electrical stimulation at the right ventricular apex. The electrogram in the left ventricular aneurysm showed delayed activities and the fastest depolarization. Entrainment was observed by faster pacing. Left ventriculography showed a large aneurysm and normal coronary arteries. Congenital left ventricular aneurysm is the most likely clinical diagnosis given the lack of past history of chest pain, myocarditis, cardiomyopathy, etc. Congenital aneurysm which presents as ventricular tachycardia is very rare, and has never been reported in an Asian. Medical management has thus far been successful.

Bundle-Branch Block↗