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Biomedical subjects

I Kodama

Publications and source records attributed to I Kodama.

At least 181 records · Page 10Linked to original sources
PubMed1989

Inhibitory effects of TYB 3823, a new antiarrhythmic agent, on mechanical responses in the vascular smooth muscles.

1. TYB 3823 (3 x 10(-5) M to 10(-3) M) but not lidocaine (10(-4) M) inhibited the contractile response to norepinephrine in rabbit aorta in a competitive manner. On the other hand, TYB 3823 had no effect on contractile responses to histamine, 5-hydroxytryptamine, high KCl and Ca2+. 2. In rabbit aorta, TYB 3823 (10(-5) M and 10(-4) M) but not lidocaine (10(-4) M) also antagonized the ouabain-induced contraction and this action was less potent than that of phentolamine (10(-6) M). 3. In rabbit coronary arteries precontracted with KCl (40 mM), either TYB 3823 or lidocaine inhibited the isoproterenol-induced relaxation to the same levels. Propranolol at 10(-8) M shifted the relaxation curve for isoproterenol to the right and at 10(-6) M it almost completely prevented the relaxation. Further, the effect of a combined treatment with propranolol (10(-8) M) and TYB 3823 (3 x 10(-5) M) was not different from that of a single treatment with propranolol (10(-8) M). 4. In rabbit iliac arteries, TYB 3823 (3 x 10(-5) M and 10(-4) M) but not lidocaine (10(-4) M) suppressed the contractile response to caffeine in a Ca2+-free medium with EGTA and nifedipine. Nitroglycerin (10(-4) M) also inhibited the response but this action was less potent than that of TYB 3823. The combined treatment of the tissue with TYB 3823 and nitroglycerin (both 10(-4) M) further inhibited the responses to caffeine as compared to a single treatment with each drug. 5. These results suggested that TYB 3823 may interfere with the responses due to the mobilization of intracellular Ca2+ activated by caffeine and also has both alpha- and beta-adrenoceptor blocking actions on the vascular smooth muscles.

Animals↗
PubMed1989

Electrophysiological effects of FK664, a new cardiotonic agent, on preparations from guinea pig ventricle and from rabbit sino-atrial node.

Effects of the cardiotonic agent FK664, 6-(3, 4-dimethoxy-phenyl)-1-ethyl-4-mesitylimino-3-methyl-3,4-dihydro-2 (1H)-pyrimidone, on isolated guinea pig ventricular muscles and rabbit sinus node pacemaker cells were studied using micro-electrode techniques. In ventricular muscles driven at 0.5-1.0 Hz, FK664 above 3 mumol.litre-1 caused an increase in contractile force and a shortening of time to peak tension. This positive inotropic effect of FK664 was accompanied by a slight elevation of the early plateau phase of the action potential, while other action potential variables were unaffected. The change in contractile force induced by FK664 was abolished in a low Ca2+ medium (0.12 mmol.litre-1) or by treatment with ryanodine (2 mumol.litre-1), whereas it was relatively well preserved in the preparations pretreated with nefedipine (1 mumol.litre-1). The slow action potentials induced by isoprenaline (0.3 mumol.litre-1) in high K+ medium (30 mmol.litre-1) and the slow inward current measured by single sucrose gap voltage clamp at a holding potential of -40 mV were unaffected by FK664. In sinus node pacemaker cells, FK664 (1-10 mumol.litre-1) caused a dose dependent acceleration of phase 4 depolarisation and a shortening of spontaneous firing cycle length. This positive chronotropic effect of FK664 was markedly inhibited in a low Ca2+ medium (0.3 mmol.litre-1). These findings suggest that FK664 has positive inotropic and chronotropic effects on the heart, due to an enhancement of transsarcolemmal calcium influx through the low threshold, dihydropyridine insensitive Ca2+ channel population.

Action Potentials↗
PubMed1989

Effects of propafenone on electrical and mechanical activities of single ventricular myocytes isolated from guinea-pig hearts.

1. The effects of propafenone on the transmembrane action potential and sarcomere shortening during twitch contraction were investigated in single ventricular myocytes isolated from guinea-pig hearts. 2. Propafenone at low concentrations (3-5 x 10(-7) M) slightly lengthened action potential duration (APD), but shortened it at higher concentrations. The shortening of APD was accompanied by an attenuation of sarcomere shortening during twitch contraction. 3. Propafenone (greater than 10(-6) M) caused a concentration-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential. In the presence of propafenone (3 x 10(-6) M), trains of stimuli led to an exponential decline in Vmax. A time constant for the recovery of Vmax from the use-dependent block was 4.8 s. 4. In myocytes treated with propafenone (3 x 10(-6) M), the Vmax of test action potentials preceded by the conditioning clamp pulses to 0 mV was progressively decreased by increasing the duration of single clamp pulse or by increasing the number of multiple brief clamp pulses. 5. These findings suggest that propafenone has use-dependent inhibitory action on the sodium channel by binding to the channel during both activated and inactivated states, and that the unbinding rate is comparable to that of Class-I antiarrhythmic drugs with intermediate kinetics. Propafenone may also have an inhibitory action on calcium and potassium channels.

Action Potentials↗
PubMed1989

Electrophysiological effects of OPC-88117, a new antiarrhythmic agent on papillary muscles and single ventricular myocytes isolated from guinea-pig hearts.

1. The effects of OPC-88117, a new antiarrhythmic agent, on transmembrane action potentials were examined in right ventricular papillary muscles and in single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, OPC-88117 above 3 x 10(-6) M caused a dose-dependent prolongation of action potential duration (APD). 3. OPC-88117 above 3 x 10(-5) M caused a significant decrease in the maximum upstroke velocity (Vmax) of the action potential without affecting the resting membrane potential. The inhibition of Vmax was enhanced at higher stimulation frequencies. 4. In the presence of OPC-88117, trains of stimuli at rates greater than or equal to 1.0 Hz led to a use-dependent inhibition of Vmax with rapid onset. The time constant for the recovery of Vmax from the use-dependent block was 456 ms. 5. The curves relating membrane potential and Vmax were shifted by OPC-88117 to the direction of more negative potentials (9 mV at 10(-4) M). 6. In single ventricular myocytes treated with OPC-88117 (1-3 x 10(-4) M), the Vmax of test action potentials preceded by conditioning clamp pulses to 0 mV was decreased progressively as the clamp pulse duration was prolonged. 7. These findings suggest that the primary electrophysiological effect of OPC-88117 on the cardiac muscle cell is prolongation of APD (Class III action) and that at high concentrations, it may also possess a lignocaine-like sodium channel inhibitory effect (Class I action).

Action Potentials↗
PubMed1989

Effects of OPC-88117, a new antiarrhythmic agent, on the electrophysiological properties of rabbit isolated hearts.

1. Effects of a new antiarrhythmic agent, OPC-88117, on the conduction properties and excitability of Langendorff-perfused rabbit hearts were compared with those of lignocaine. 2. OPC-88117 above 10(-5) M caused a significant prolongation of atrio-His bundle conduction time (A-H interval) as well as His bundle-ventricular conduction time (H-V interval). Lignocaine above 10(-5) M caused a similar prolongation of H-V interval with a minimum change of A-H interval. The conduction time from His bundle stimulus to the left ventricle (St-LV) at a low frequency (1 Hz) was also prolonged by these drugs around 10(-4) M. 3. OPC-88117 above 3 x 10(-6) M prolonged the effective and functional refractory periods of His bundle (ERPHB, FRPHB) as well as the effective refractory period of left ventricular muscle (ERPVM) in a dose-dependent manner. ERPHB, FRPHB and ERPVM were shortened by low concentrations of lignocaine (3 x 10(-6)-10(-5) M), but were prolonged by high concentrations (3 x 10(-5)-10(-4) M). 4. Lignocaine (3 x 10(-6)-10(-4) M) induced an upward displacement of the His bundle refractory curve, indicating a greater intraventricular conduction delay for premature excitation. In experiments with OPC-88117, such an upward displacement was observed only at 10(-4) M. 5. These results suggest that the primary electrophysiological effect of OPC-88117 is a lengthening of ventricular refractoriness, and that at high concentrations it may also exert lignocaine-like inhibition of ventricular conduction.

Animals↗
PubMed1989

Surgical management of residual gastric cancer.

From 1966 to 1985, 2130 patients with gastric cancer were admitted to our surgical department. Among these cancers, gastric cancer following partial gastrectomy for benign gastroduodenal lesion were present in 22 (1%) patients. The original pathology was gastric ulcers in 64% (14 patients), duodenal ulcers in 23% (5 patients), combined gastric and duodenal ulcers in 9% (2 patients), and leiomyoma of the gastric cardia in 4% (1 patient). Fourteen patients were reconstructed by Billroth II, 7 by Billroth I, and one had an esophagogastrostomy after a proximal gastrectomy. The cancer in 19 (86%) patients was resected and 3 (14%) could not be resected. Only 2 (9%) were early cancer, 20 (89%) were advanced cancer including 11 (50%) with Borrmann type 3. A higher proportion of positive lymphnode metastasis was observed for residual gastric cancer (84%) than for primary gastric cancer (49%). The overall 5-year survival rate was 32%, with a 5-year survival rate of 45% for those who underwent curative resection.

Aged↗
PubMed1989

Electrophysiologic effects of TYB-3823, a new antiarrhythmic agent, on isolated guinea pig ventricular muscles.

The effects of a newly synthesized antiarrhythmic agent, TYB-3823 on the transmembrane action potential were examined in isolated papillary muscles of guinea pig. TYB-3823 (3 x 10(-6)-3 x 10(-5)M) caused a dose-dependent decrease in the maximum upstroke velocity (Vmax) and a shortening of action potential duration (APD). In the presence of TYB-3823, trains of stimuli at rates greater than or equal to 0.2 Hz led to an exponential decline in Vmax. This use-dependent block was enhanced at higher stimulation frequency. The time constant for the recovery of Vmax from the use-dependent block was 12.6-13.4 s. The curves relating membrane potential and Vmax were shifted by TYB-3823 (3 x 10(-5)M) to the direction of more negative potentials (5.7 mV). In preparations treated with TYB-3823 (10(-5)-3 x 10(-5) M), the Vmax of test action potentials preceded by conditioning clamp pulses to 0 mV was progressively decreased by increasing the duration of a single clamp pulse or by increasing the number of multiple brief clamp pulses. These findings suggest that TYB-3823 has use- and voltage-dependent inhibitory action on the fast sodium channel by binding to the channel during its activated and inactivated states, and that the unbinding rate of the drug from the channel is very slow. Such characteristics of sodium channel block in combination with APD shortening effect would provide unique antiarrhythmic activities of this substance.

Action Potentials↗
PubMed1988

Rapid methylation of genomic DNA in proliferating T-cells from bovine thymocytes.

Two subpopulations of bovine calf thymus cells were separated by buoyant density centrifugation. The low-density cells (L-cells) showed high response to T-cell mitogens, while the high density cells (H-cells) did not. The DNA-metabolizing enzyme activities were elevated 10-fold in L-cells in comparison with those in H-cells. L-cells contained a DNA-replicating complex, DNA replitase, while H-cells did not. These observations suggested that L-cells were proliferating, mature T-cells and H-cells were dying intrathymic cells. A DNA methyltransferase was associated with DNA replitase in L-cells. In order to determine whether replitase-associated DNA methyltransferase functions at replicating regions, the methylation pattern of genomic DNA of L-cells was compared with that of H-cells. No significant difference was found in the extent of CpG dinucleotide methylation, and in the location of mC in the satellite I DNA sequence as identified by Southern hybridization and direct sequencing. Thus the majority of methylation patterns of genomic DNA did not change during T-cell development in the thymus. The results indicated that the methylation patterns were rapidly maintained in proliferating T-cells. Although methods employed in the present study might not be sensitive enough to detect transient hemimethylation, it is suggested that the rapid methylation might be catalyzed, albeit not completely, by a DNA methyltransferase associated with the DNA replitase complex.

Animals↗
PubMed1988

Frequency and voltage dependent effects of AN-132, a new class I anti-arrhythmic agent, on Vmax of action potential upstroke in guinea pig ventricular muscles.

The in vitro electrophysiological properties of a newly synthesised antiarrhythmic agent, AN-132, were evaluated by recording transmembrane action potentials from guinea pig papillary muscles. AN-132 (10-100 mumol.litre-1) caused a dose dependent decrease in the maximum upstroke velocity (Vmax) of the action potential without affecting the resting potential. In the presence of AN-132, trains of stimuli at rates greater than or equal to 0.1 Hz led to an exponential decline in Vmax. This use dependent block was enhanced at higher stimulation frequency. The time constant for the recovery of Vmax from the use dependent block was 39.5-41.2 s. The curves relating membrane potential and Vmax were shifted by AN-132 (100 mumol.litre-1) in the direction of more negative potentials (6.1 mV). In preparations treated with AN-132 (30 and 100 mumol.litre-1), the Vmax of test action potentials preceded by conditioning clamp pulses to 0 mV was progressively decreased with an increasing number of pulses. A single prolonged clamp pulse to 0 mV reduced Vmax much less than multiple brief clamp pulses. These findings suggest than AN-132 has use dependent inhibitory action on the fast sodium channel by binding to the channel mainly during its activated state and that the unbinding rate of the drug during diastole is very slow. This use dependency and its greater inhibition of Vmax in depolarised muscles through the increase in tonic block may play a major role in preventing ventricular arrhythmias.

Action Potentials↗
PubMed1988

Electrophysiological effects of KT-362, a new antiarrhythmic agent with vasodilating action, on isolated guinea pig ventricular muscle.

The effects of KT-362, a newly synthesized vasodilating and antiarrhythmic agent, on transmembrane action potentials were examined in isolated papillary muscles of guinea pig. KT-362 (3 x 10(-6) to 3 x 10(-5) M) caused a dose-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential without affecting the resting potential. In the presence of KT-362, trains of stimuli at rates greater than or equal to 0.2 Hz led to an exponential decline in Vmax. This use-dependent block was enhanced at higher stimulation frequency. The time constant for the recovery of Vmax from the use-dependent block was 2.8-2.9 s. The curves relating membrane potential and Vmax were shifted by KT-362 (10(-5) M) in the direction of more negative potentials (8.6 mV). In papillary muscles treated with KT-362 (10(-5) M), the Vmax of test action potential preceded by conditioning clamp pulses to 0 mV was progressively decreased with increasing number of pulses, while it was little affected by the duration of each clamp pulse within the range from 10 to 700 ms. These findings suggest that KT-362 has quinidine-like use-dependent inhibitory action on the fast sodium channel of cardiac muscles by the binding to the channel mainly during its activated state. At high concentrations (greater than or equal to 3 x 10(-5) M), KT-362 also suppressed the slow action potential in K+ depolarized papillary muscles.

Action Potentials↗
PubMed1988

Effects of bepridil on ventricular depolarization and repolarization of rabbit isolated hearts with particular reference to its possible proarrhythmic properties.

1. Effects of bepridil on ventricular depolarization and repolarization sequences were examined in rabbit Langendorff-perfused hearts. 2. In distant bipolar electrograms (DBEs), bepridil, 10(-6) M, caused a significant prolongation of QT intervals. At 10(-5) M, the QT prolongation was further enhanced, and a significant prolongation of QRS duration was also observed. Polymorphous ventricular tachycardia was frequently induced by a single premature stimulus at the higher concentration. 3. In epicardial electrograms recorded through modified bipolar electrodes, bepridil, 10(-6) M, prolonged the interval from the peak negative deflection of the QRS complex to the apex of the T wave (Q-aT), which corresponded to the intracellular action potential duration at 90% repolarization (APD90). The Q-aT prolongation was larger in the base than in the apex, resulting in a marked distortion and dispersion of repolarization. The epicardial activation sequence was unaffected. 4. At 10(-5) M bepridil, the dispersion of repolarization was much more enhanced by activation delay in the epicardial surface. 5. These findings suggest that bepridil causes regionally different lengthening of APD in ventricular muscle leading to an increase in temporal dispersion of repolarization, and that this dispersion may be inducive for re-entrant arrhythmias when accompanied by slow conduction at toxic doses.

Animals↗
PubMed1988

Inhibitory effects of nitroglycerin on contractile responses to methoxamine and clonidine in isolated rabbit renal and femoral arteries.

The inhibitory effect of nitroglycerin (NG) on contractile responses to methoxamine (MO) and clonidine (CL) was investigated in isolated rabbit renal and femoral arteries. NG (10(-7)-10(-5) mol/l) inhibited the responses to MO and CL in a noncompetitive manner and its inhibitory effect on CL-responses was much greater than that on the MO-responses. In the presence of phenoxybenzamine, however, NG (10(-5) mol/l) markedly inhibited the residual response to MO. Contractile responses to KCl or added Ca2+ in a Ca2+-free medium containing KCl were slightly inhibited by NG. In the presence of nifedipine, NG (10(-5) mol/l) markedly inhibited residual responses to CL but it only slightly inhibited the response to MO. In a Ca2+-free medium with EGTA, MO (10(-5) mol/l) or CL (10(-5) mol/l) induced a phasic contraction. NG had a greater inhibitory effect on the response to CL than MO. In a Ca2+-free medium with EGTA, nifedipine and MO (10(-5) mol/l) or CL (10(-5) mol/l), Ca2+ induced a tonic contraction. NG inhibited the Ca2+-response in the presence of CL, but it had little or no effect on the Ca2+-response in the presence of MO. These results suggest that in rabbit renal and femoral arteries, the potent inhibitory effect of NG on the responses to CL as compared to MO may be due to differences in the amount of receptor reserves that exist for both the agonists. In addition, the inhibition of voltage-dependent Ca2+ channels may not play a major role in the vasoinhibitory action of NG. Further, NG inhibits contractile responses due to mobilization of intracellular Ca2+ much more than the responses due to receptor-activated, nifedipine-insensitive Ca2+-movement.

Animals↗
PubMed1988

Diverse characteristics in potential waveform of His-Purkinje system--experimental and simulation studies.

Reflection to the body surface of the single beat-potentials of the His-Purkinje system (HPS) was analysed by a single beat recording of the epicardial HPS potentials from the Langendorff perfused canine heart and by the reconstruction of HPS potentials on the basis of the cable concept. Unipolar epicardial HPS potentials from 8 leads distributed equidistantly over the basal region of the ventricles were amplified by a high gain (120 dB) amplifiers with an active bandpass filter (40-2400 kHz). The waveform of these HPS potentials differed in each lead. The largest (42 +/- 8 microV, mean +/- SE, n = 5) of these HPS potentials, which was obtained from the anterior free wall of the right ventricle, was composed of two peaks: the initial slow- and positive-peak and the late sharp- and negative-peak. The former peak appeared 12 +/- 3 msec (mean +/- SE, n = 5) ahead of the spike of the His-bundle electrogram (HBE) recorded from the close bipolar electrodes which were attached intracavitally along the membrane portion of the His-bundle. The latter appeared in coincidence with the spike of HBE. The extracellular potentials generated by HPS excitation were calculated by assuming that the excitation proceeds along the three dimensionally reconstructed HPS. The simulated waveform was in agreement with those of the epicardial HPS potentials. Thus, the HPS potentials on the body surface may inscribe a diverse waveform as a reflection of the complexed architecture of the whole HPS.

Action Potentials↗
PubMed1988

Block of cardiac sodium channels by antiarrhythmic drugs.

The effects of seven Class-I antiarrhythmic drugs on the maximum upstroke velocity (Vmax) of action potential were examined in isolated guinea pig ventricular muscles in order to characterize their use- and state-dependent sodium channel blocking action. From the onset and offset kinetics of the use-dependent Vmax inhibition during stimulation trains, the seven drugs were subdivided into two groups; fast drugs (lidocaine, mexiletine, and tocainide), and slow drugs (quinidine, aprindine, disopyramide and flecainide). In experiments to assess the state-dependent sodium channel block, a conditioning clamp pulse to 0 mV was applied by using the single sucrose-gap voltage-clamp technique, and the Vmax of test action potential 100 msec after the clamp pulse was measured. The decrease in Vmax by 10 msec clamp pulse was defined as the activated channel block (ACB), and the decrease in Vmax as the clamp pulse duration was prolonged from 10 to 500 msec was defined as the inactivated channel block (ICB). The ratio of ICB to ACB was less than 1.0 for quinidine, disopyramide and flecainide, and much greater than 1.0 for aprindine, lidocaine, mexiletine, and tocainide. These characteristics may contribute to the differences in efficacy of each drug in treating various types of arrhythmias.

Action Potentials↗
PubMed1987

Block of activated and inactivated sodium channels by class-I antiarrhythmic drugs studied by using the maximum upstroke velocity (Vmax) of action potential in guinea-pig cardiac muscles.

The inhibitory effect of disopyramide, quinidine, mexiletine, lidocaine, tocainide and aprindine on the maximum upstroke velocity (Vmax) of action potential was examined in isolated guinea-pig cardiac muscles in terms of their sodium channel block during activated and/or inactivated state. In right ventricular papillary muscles, a conditioning clamp pulse was applied from the resting potential to 0 mV level using the single sucrose-gap voltage clamp technique, and Vmax of test action potential elicited 100 ms after termination of the clamp pulse was measured as an index of sodium channel availability. Such clamp pulses caused various Vmax decreases in the presence of the six drugs. The decrease in Vmax by 10 ms clamp pulse was defined as the activated channel block (ACB), and the decrease in Vmax as the clamp pulse duration was prolonged from 10 to 500 ms was defined as the inactivated channel block (ICB). The ratio of ICB to ACB was less than 1.0 (0.36-0.51) for disopyramide and quinidine, and much greater than 1.0 (2.61-11.23) for mexiletine, lidocaine, tocainide and aprindine. From these findings it was suggested that the former group of drugs may block the sodium channel mainly during the upstroke phase of action potential, while the latter do so mainly during the plateau phase. This assumption was confirmed by experiments comparing the potency of Vmax inhibition in atrial and ventricular muscles isolated from the same guinea-pig heart.

Action Potentials↗
PubMed1987

Frequency- and voltage-dependent effects of aprindine on the upstroke velocity of action potential in guinea pig ventricular muscles.

The effects of aprindine on transmembrane action potentials were examined in isolated papillary muscles of guinea pig. Aprindine (10(-6)-10(-5) M) caused a dose-dependent decrease in the Vmax of the action potential without affecting the resting potential. In the presence of aprindine, trains of stimuli at rates greater than 0.1 Hz led to an exponential decline in Vmax. This use-dependent block was enhanced at the higher stimulation frequency. The time constant for the recovery of Vmax from the use-dependent block (offset) was 6.2-7.8 s. In depolarized papillary muscles with high [K+]o, the inhibitory action of aprindine on Vmax after a long quiescent period (tonic block) was augmented markedly, but the rates of onset and offset of the use-dependent block were similar to those in normally polarized preparations. The curves relating membrane potential and Vmax were shifted by 7.3 mV with aprindine at 3 X 10(-6) M in the direction of more negative potentials. These findings suggest that aprindine has quinidinelike use-dependent inhibitory action on the fast sodium channels of cardiac muscles. This use-dependency and its greater inhibition of Vmax in depolarized muscles through the augmentation of tonic block may play a major role for the drug action to prevent ventricular arrhythmias.

Action Potentials↗
PubMed1987

Effects of activation sequence and anisotropic cellular geometry on the repolarization phase of action potential of dog ventricular muscles.

The influence of activation sequences on action potential configuration, especially in the repolarization phase, was examined in isolated canine ventricular muscles. Action potentials were recorded from the epicardial surface in the center of a preparation having nearly uniform fiber orientation (25 X 25 mm). Stimuli applied just adjacent to the recording site produced nearly centrifugal propagation. An activation sequence either parallel (longitudinal) or perpendicular (transverse) to the long axis of the muscle fibers was produced by peripheral stimulation. Action potential duration at -60 mV (APD-60 mV) during centrifugal propagation was significantly longer than that during longitudinal propagation. Further shortening of APD-60 mV was observed during transverse propagation. When a collision of longitudinal or transverse wavefronts (longitudinal or transverse collision) was produced at the action potential recording site, the shortest APD was recorded. During centrifugal propagation, action potential mapping around the stimulating electrodes revealed that APD-60 mV shortened gradually as the recording site was moved further from the stimulation site. The spatial gradient of APD was steeper in the transverse than in the longitudinal direction, causing a distortion in the repolarization sequence and the recovery of excitability near the center of the tissue. Premature stimuli applied to an area near the central stimulation site induced one-way block and circus movement of the wavefront, indicating reentry of excitation. We concluded that the activation sequence and anisotropic cellular geometry substantially affect APD, and that such a change contributes to the spatial inhomogeneity of refractoriness leading to reentrant arrhythmias.

Action Potentials↗