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Biomedical subjects

I Kodama

Publications and source records attributed to I Kodama.

At least 109 records · Page 6Linked to original sources
PubMed1996

[Autonomic regulation of pacemaker activity in the sinoatrial node].

Recent technical advances have made it possible to investigate quantitatively the ionic events underlying pacemaker activity in the sinoatrial node. Various time-dependent currents through ion channels such as the delayed rectifier K current, two types of Ca currents and the hyperpolarization-activated current have been found to play an important role in the generation of the pacemaker activity of sinoatrial node cells. Time-independent background currents, transporter-mediated current and pump current also contribute to pacemaker activity. In this article, the physiological significance of these currents for the pacemaker depolarization and their modulation by autonomic nerves and humoral factors are discussed.

Autonomic Nervous System↗
PubMed1996

[Immunohistochemical analysis of c-erB-2 and nm23 expression in early gastric carcinoma].

The expression of c-erB-2 and nm23 genes product were investigated immunohistochemically in 108 resected cases of early gastric cancer. The expression rate of c-erB-2 was significantly higher in the cases of submucosal cancer or in the cases with lymph node metastasis. The expression rate of c-erB-2 was higher in the metastatic tumor than in the primary tumor. There was no significant correlation between the expression of nm23 and depth of invasion. The expression rate of nm23 was lower in the cases with lymph node metastasis than in the cases without lymph node metastasis. The expression could not be found in the metastatic tumor. These results suggest that there would be correlation between the expression of c-erB-2 and depth of invasion and lymph node metastasis, and the nm23 may suppress metastatic potential in early gastric cancer.

Humans↗
PubMed1995

Computer simulation of the electrotonic modulation of pacemaker activity in the sinoatrial node by atrial muscle.

Electrotonic interaction between the sinoatrial (SA) node and surrounding atrial muscle was investigated in a computer simulation using a modified Oxsoft HEART model (Oxsoft, Oxford, UK). When an SA node cell model was coupled to a passive atrial membrane model (RC circuit) with various coupling conductances (Gc), there was a Gc-dependent prolongation of spontaneous cycle length (SCL). At a sufficiently high value of Gc, the spontaneous activity was finally stopped. A nonlinear relationship between Gc and SCL was obtained, similar to that observed in experiments on rabbit SA node cells. When the muscarinic potassium current (iK,ACh) was activated in the SA node cell model, the coupling-induced inhibition of pacemaker activity was potentiated. Although coupling current and iK,ACh were additive, their effects on SCL were more than additive because of the nonlinear dependence of SCL on net current. A decrease in the input resistance of the atrial membrane model to stimulate the activation of iK,ACh in atrial muscle was also shown to potentiate the coupling-induced inhibition of SA node spontaneous activity.

Action Potentials↗
PubMed1995

Complex frequency-dependent interaction of class-I antiarrhythmic drugs as they affect intraventricular conduction.

We investigated the interaction of class-I antiarrhythmic drugs as they affect intraventricular conduction of human hearts in vivo. QRS duration in signal-averaged electrocardiograms and standard electrocardiograms were measured as an index of intraventricular conduction time in 17 patients with implanted pacemakers at various pacing rates (100-180 ppm, VVI mode). Single intravenous administration of lidocaine, disopyramide or aprindine prolonged the QRS of signal-averaged electrocardiograms in a frequency-dependent manner. Lidocaine (n = 17) produced significant QRS prolongation from pre-drug control at rates > or = 120 ppm (6.2 +/- 1.4% at 180 ppm), whereas disopyramide (n = 17) and aprindine (n = 17) did so from the lowest rate (8.9 +/- 1.8% to 12.3 +/- 2.9% at 100-180 ppm with disopyramide; 14.7 +/- 1.3% to 19.3 +/- 2.2% at 100-180 ppm with aprindine). Addition of lidocaine to disopyramide (n = 17) showed an additive effect; QRS prolongation was enhanced significantly by 1.4-2.8% at rates > or = 150 ppm. In contrast, addition of lidocaine to aprindine (n = 17) showed a subtractive effect; the QRS prolongation was attenuated significantly by 1.6-2.4% at rates < 150 ppm. Combined intravenous administration of class-I antiarrhythmic drugs causes not only additive but also subtractive effects on the intraventricular conduction of the human heart, probably through their interaction on the sodium channel receptor.

Aged↗
PubMed1995

Electrophysiological effects of SD-3212, a new antiarrhythmic agent with vasodilator action, on guinea-pig ventricular cells.

1. The effects of SD-3212 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, SD-3212 > or = 3 microM caused a significant decrease in the maximum upstroke velocity (Vmax) of action potential without affecting resting membrane potential. The inhibition of Vmax was enhanced at higher stimulation frequencies. 3. In the presence of SD-3212, trains of stimuli at rates > or = 0.5 Hz led to a use-dependent inhibition of Vmax. The time constant for the recovery of Vmax from the use-dependent block was 1.3 s. 4. Voltage-dependence of Vmax inhibition by SD-3212 was investigated in single myocytes. The curves relating membrane potential and Vmax were shifted by SD-3212 (10 microM) in a hyperpolarizing direction by 6.2 mV. 5. In myocytes treated with SD-3212 (10 microM), the Vmax of test action potentials preceded by conditioning clamp to 0 mV was decreased progressively as the clamp pulse duration was prolonged. Vmax of test action potentials following a long (1 s) 0 mV clamp recovered at a time constant ranging from 1.01 to 1.22 s, being shorter at the more negative potential within a range from -70 to -90 mV. 6. These findings suggest that the primary electrophysiological effect of SD-3212 is a use- and voltage-dependent inhibition of sodium channels. From the onset and offset kinetics of the use-dependent block, SD-3212 is located between fast and intermediate kinetic Class-I drugs. From the state-dependence of sodium channel block, SD-3212 belongs to inactivated channel blockers.

Action Potentials↗
PubMed1995

Electrophysiological effects of Ro 22-9194, a new antiarrhythmic agent, on guinea-pig ventricular cells.

1. Cardiac effects of Ro 22-9194 were examined in papillary muscles and single ventricular myocytes isolated from guinea-pigs and compared with those of moricizine. 2. In papillary muscles, both Ro 22-9194 (> or = 10 microM) and moricizine (> or = 1 microM) caused a significant dose-dependent decrease in the maximum upstroke velocity (Vmax) and a shortening of the action potential duration. 3. In the presence of either drug, trains of stimuli at rates > or = 0.2 Hz led to an exponential decline in Vmax. This use-dependent block was enhanced at higher stimulation frequencies. A time constant (tau R) for Vmax recovery from the use-dependent block was 9.3 s for Ro 22-9194 and 26.4 s for moricizine. 4. The curves relating membrane potential and Vmax in single myocytes were shifted by Ro 22-9194 (30 microM) or by moricizine (3 microM) in a hyperpolarizing direction by 8.4 mV and 8.0 mV respectively. 5. In myocytes treated with Ro 22-9194 (30 microM), a 10 ms conditioning clamp to 0 mV caused a significant decrease in Vmax of the subsequent test action potential; further prolongation of the clamp pulse duration resulted in a modest enhancement of the Vmax inhibition. In the presence of moricizine (3 microM), a similar conditioning clamp > 200 ms caused a significant Vmax reduction; the longer the clamp pulse duration, the greater the Vmax reduction. 6. Ro 22-9194 > or = 30 microM caused a slight decrease of calcium inward current (ICa) of myocytes without affecting the delayed rectifier potassium current (IK). 7. These findings suggest that the primary electrophysiological effect of Ro 22-9194 as an antiarrhythmicagent is, like moricizine, a use- and voltage-dependent inhibition of sodium channels. From the onset and offset kinetics of the use-dependent block, Ro 22-9194 belongs to the intermediate kinetic Class I drugs, while moricizine is a slow kinetic drug. From the state-dependence of sodium channel block, Ro 22-9194 may belong to activated channel blockers, while moricizine belongs to inactivated channel blockers.

Action Potentials↗
PubMed1995

Modulation of pacemaker activity of sinoatrial node cells by electrical load imposed by an atrial cell model.

To investigate the electrotonic modulation of sinoatrial (SA) node pacemaker activity by atrial muscle, single or multiple (2-7) SA node cells isolated from rabbit hearts were connected to a membrane model [resistance-capacitance (R-C) circuit] of an atrial cell through an external circuit that mimics the gap junctional conductance (Gc) between cells. When Gc was 0 nS (uncoupled conditions), all the preparations generated regular and stable spontaneous action potentials with a mean cycle length (SCL) of 263 +/- 45 ms (+/- SD, n = 35). Step increases of Gc were associated with a progressive prolongation of SCL. At sufficiently high values of Gc, the spontaneous activity became irregular and finally stopped. We defined the threshold Gc causing an appreciable SCL irregularity as the minimum Gc at which the ratio of SD to mean of SCL was > 0.3. The threshold Gc for a single SA node cell was calculated to be 0.58 nS. In the presence of acetylcholine (ACh; 0.05-0.2 microM), the coupling-induced inhibition of spontaneous activity was greatly increased, and the threshold Gc for a single SA node cell was decreased in a concentration-dependent manner. These findings show that the pacemaker activity of SA node cells is easily inhibited when the cells are coupled to a passive atrial cell model and the inhibition is amplified by ACh. Computer simulation using a modified Oxsoft HEART model indicates that the passive atrial cell model acts as a current sink, imposing a substantial outward current on the SA node cell, and ACh amplifies the effect by activating an additional outward current.

Acetylcholine↗
PubMed1995

Early mucosal gastric cancer with lymph node metastasis.

From 1976 to 1992, a total of 358 cases of mucosal early gastric cancer (m-cancer) were treated by resection in the First Department of Surgery, Kurume University Hospital. Eight (2.2%) of these 358 cases of m-cancer were associated with lymph node metastasis. In these 358 cases, the mean diameter of the tumor was 2.75 cm, and the mean age was 59.6 years. In the 8 cases of m-cancer with positive lymph node metastasis (n(+)), the mean diameter was 5.2 cm and the mean age was 51.6 years. Seven (87.5%) out of the 8 cases of m-cancer with n(+) were IIc macroscopic cancer type and were associated with ulcer and/or ulcer scar.

Adenocarcinoma↗
PubMed1995

Resected early gastric cancer--clinicopathological studies on 610 cases.

A total of 610 cases of early gastric cancer were studied, retrospectively. Of these, 541 (88.7%) cases were single and 62 (10.1%) cases were multiple cancers. Lymph node metastasis occurred in 11.2% of the elevated, in 8.2% of the depressed and in 15.1% of the mixed type. There was no lymph node metastasis when a mucosal or submucosal cancer was less than 10 mm in diameter. By contrast, in the cases in which the preoperative diagnosis was suspected advanced cancer, the incidence of lymph node metastasis was high, at 33%. Therefore, when the preoperative diagnosis is advanced cancer, standard radical gastrectomy and/or extended radical gastrectomy should be selected even though they are found to be early gastric cancer. The age-corrected 5-year survival rate was 98.5% in the cases with no lymph node metastasis and 93.0% in the cases with lymph node metastasis (p > 0.05). The 5-year survival rate was 100% in mucosal cancer and 95.5% in submucosal cancer (p > 0.05).

Adult↗
PubMed1995

Ionic basis of the chronotropic effect of acetylcholine on the rabbit sinoatrial node.

OBJECTIVE: The aim was to study the ionic basis of the chronotropic effects of bath applied acetylcholine and vagal stimulation on the rabbit sinoatrial node. METHODS: The chronotropic effect of bath applied acetylcholine was measured in single cells and small multicellular preparations from the rabbit sinoatrial node and the chronotropic effect of postganglionic vagal stimulation was measured in the intact sinoatrial node. The roles of the hyperpolarisation activated current, i(f), the acetylcholine activated potassium current, iK,ACh, and the L-type calcium current, iCa, were investigated by blocking the currents with 1-2 mM Cs+ or 10(-6) M UL-FS49, 0.2-1.0 mM Ba2+, and 6 x 10(-6) M nifedipine, respectively. RESULTS: Under control conditions, small multicellular preparations were approximately two orders of magnitude less sensitive to bath applied acetylcholine than single cells. However, after block of acetylcholinesterase by eserine in small multicellular preparations the sensitivities of the two types of preparation were approximately the same. Block of i(f) either had no discernible effect or increased the chronotropic effect of bath applied acetylcholine on single cells or small multicellular preparations, whereas partial block of iK,ACh reduced it substantially. Similarly, block of i(f) did not suppress the initial slowing of spontaneous action potentials by vagal stimulation, whereas partial block of iK,ACh reduced it. The hyperpolarisation of the arrested sinoatrial node in response to vagal stimulation was also substantially reduced by block of iK,ACh. Partial block of iCa caused large decreases in the action potential amplitude and maximum diastolic potential, but little decrease in the rate of spontaneous action potentials, and therefore did not mimic the effect of acetylcholine. CONCLUSIONS: The chronotropic effects of bath applied acetylcholine and vagal stimulation are not principally the result of a suppression of i(f) or iCa, whereas the activation of iK,ACh may play an important role.

Acetylcholine↗
PubMed1994

Ca(2+)-calmodulin mediated modulation of the electrical coupling of ventricular myocytes isolated from guinea pig heart.

The mechanism for the regulation of junctional conductance (gj) by Ca2+ was examined in paired ventricular myocytes isolated from guinea pig heart. One cell of the pair was voltage-clamped by a single-patch pipette, and gj was measured after perforation of the non-junctional membrane of the partner cell. The average value of gj under control condition at pCa 9.0 was 181 +/- 13 nS (n = 30). An elevation of calcium concentration ([Ca2+]i) in the intracellular perfusate from pCa 9.0 to pCa 5.7 resulted in a decrease of 32 +/- 5% in gj (n = 18). In myocytes pretreated with W7 (10(-4) M), a similar elevation of [Ca2+]i caused a decrease of only 10 +/- 3% in gj (n = 6), indicating a protective action of W7 against Ca(2+)-mediated electrical uncoupling. W5 (10(-4) M), a non-chlorinated derivative of W7, did not show such a protective action. Calmodulin (10(-5) M) had no effects on gj at pCa 9.0. However, at moderately elevated [Ca2+]i condition at pCa 7.0, calmodulin (10(-5) M) decreased gj by 29 +/- 6% (n = 4). These results suggest that calmodulin may play an important role in the Ca(2+)-mediated regulation of gap junctional channel function in the cardiac ventricular cells.

Action Potentials↗
PubMed1994

Vasoinhibitory effects of NC 1005 and NC 1006, new synthesized antiarrhythmic agents, in isolated rat aorta.

1. NC 1005 and NC 1006 (3 x 10(-6) M-10(-4) M) inhibited the contractions induced by phenylephrine (PE) and KCl in isolated rat aortas with or without endothelium. 2. In a Ca(2+)-free medium containing EGTA and nifedipine, NC 1005 and NC 1006 inhibited PE-response and a subsequent response to Ca2+ in the presence of PE. 3. NC 1005 and NC 1006 also caused relaxations of endothelium-removed aortas precontracted with PE. 4. The relaxations induced by NC 1005 and NC 1006 were potentiated by amiloride, zaprinast and theophylline but not by increasing the external Na+ concentration. 5. Methylene blue and ouabain slightly potentiated NC 1005-relaxation, but not NC 1006-relaxation. 6. Glyburide, apamine and nifedipine had no effect on the relaxations. 7. NC 1005 and NC 1006 potentiated the relaxation induced by nitroglycerin (NG) without affecting isoproterenol-relaxation. 8. In the presence of forskolin, NC 1005 and NC 1006 failed to potentiate NG-relaxation. 9. These results suggest that the vasoinhibitory effects of NC 1005 and NC 1006 may be due to an increase in the level of cAMP.

Aniline Compounds↗
PubMed1994

Aftereffects of high-intensity DC stimulation on the electromechanical performance of ventricular muscle.

To clarify the mechanisms underlying cardiac dysfunction after electrical defibrillation, we investigated the effects of direct current field stimulation (10 ms, 1-80 V/cm) on isolated guinea pig papillary muscles. Shocks (S2) > 15 V/cm lowered the plateau height of the S2-induced action potential and inhibited its terminal repolarization. Subsequent responses to basic stimuli (S1, 1.0 Hz) for 1-3 min were characterized by a decrease in the maximum diastolic potential, a shortening of action potential duration, and an increase of the developed tension. With S2 > 30 V/cm, a marked delay in repolarization of the S2-induced action potential was followed by oscillation of membrane potential, resulting in repetitive spontaneous activity and often refractoriness to S1 stimulation. The aftereffects were independent of the phase of S2 application. Most of the aftereffects were preserved in the presence of nifedipine (1 microM) or ryanodine (1 microM). Only sodium channel blockade by tetrodotoxin (10 microM) modified the aftereffects by depressing the generation of spontaneous activity. These findings suggest that strong shocks (> 15 V/cm) will produce abnormal arrhythmogenic responses probably through a transient rupture of sarcolemmal membrane (electroporation) leading to a disturbance of the ionic equilibrium of the myocyte.

Animals↗
PubMed1994

Inhomogeneity of cellular activation time and Vmax in normal myocardial tissue under electrical field stimulation.

To clarify the mechanism underlying the ectopic excitation after countershock, the cellular activation processes of cardiac tissue with a low-potential-gradient electric field (LPEF) were investigated in experiments using guinea pig papillary muscles and in computer simulation. Action potential upstrokes in papillary muscles during longitudinal propagation (LP) or transverse propagation (TP) were different from those of nonpropagating ones in single ventricular cells in terms of lower maximum upstroke velocity (Vmax) (LP, 231 V/s; TP, 309 V/s) and the presence of a linear ascending segment in the phase-plane plot. High Vmax (409 V/s) close to the single cell (512 V/s) was obtained in the muscle at the collision of LP (LC). Field stimulation of the muscles with LPEF < 5 V/cm caused inhomogeneous excitation suggesting multiple wave fronts, which collide with each other, and a wide spatial dispersion of Vmax (132-388 V/s). Phase-plane plots of action potential with lower Vmax were similar to LP or TP, whereas those with higher Vmax were similar to LC. In the two-dimensional discrete sheet composed of 51 x 51 elements of modified Beeler-Reuter model, the inhomogeneous excitation induced by LPEF is mimicked by setting a random variation of stimulus onset in each element. LPEF may induce inhomogeneous excitation with multiple wave fronts through a complex electrotonic interaction. This would provide a basis for the genesis of ectopic focal excitation.

Action Potentials↗
PubMed1994

Procainamide-induced changes in reentrant ventricular tachycardia with special reference to the tachycardia-interrupting critical paced cycle length during transient entrainment with rapid pacing.

With rapid ventricular pacing, sustained ventricular tachycardia (VT) is often entrained and interrupted at a critical paced cycle length. In this paper, the possible mechanism and determinant of the critical cycle length interrupting VT are addressed. Sixteen consecutive patients underwent rapid ventricular pacing in 18 morphologically distinct sustained VTs before and after procainamide. The VT morphology was identical before and after the drug. The VT origin was determined by endocardial mapping as the earliest site of activation of VT and an electrode catheter was located at the site. Rapid pacing was performed to entrain VT and repeated in 10 msec decrements of cycle length until VT was interrupted at a critical paced cycle length which was defined as the block cycle length. The effective refractory period was measured at the pacing site. The paced QRS duration and the local conduction time were measured and used as indices of conduction time in the normal myocardium. VT was entrained and interrupted in all patients. At the block cycle length, initial constant fusion was replaced abruptly by the fully paced QRS complex. At the same time, the local electrogram at the site of VT origin showed changes in the morphology and the timing of activation which were identical to those of the fully paced beat. This loss of fusion and the changes in the local electrogram were considered to be a result of orthodromic block and the block cycle length was assumed to represent the cycle length at which 1:1 conduction fails in the area of slow conduction. After procainamide, both the VT cycle length and the block cycle length were prolonged to a similar degree (p < 0.001) but the relative degree of change varied from patient to patient. The paced QRS duration and the conduction time were prolonged by procainamide but in smaller degrees than the cycle length of VT or the block cycle length (p < 0.02-01). The effective refractory period at the pacing site and the QT interval showed small changes after procainamide. The postrepolarization refractoriness rather than the duration of action potential can be responsible for the procainamide-induced prolongation of the block cycle length, and the block cycle length might be used as a new index to characterize the electrophysiologic property of the VT circuit and also the action of antiarrhythmic drugs.

Adolescent↗
PubMed1994

Total gastrectomy for gastric cancer: 12-year data and review of the effect of performing lymphadenectomy.

A total of 1,272 patients with gastric cancer were admitted to our institute for surgery during 12 years (1975-1986). Of these, 1,059 (83.4%) underwent gastrectomy. Among these, 252 (23.8%) were total gastrectomy (TG), involving 160 (63.5%) cases of cancer mainly located in the upper third of the stomach, 81 (32.1%) in the middle third and 11 (4.4%) in the lower third. Radical TG was performed in 65.9% and palliative TG in 34.1%. Roux-en-Y reconstruction was selected in 80%, jejunal interposition in 17.6% and double tract in 2.4%. The survival rate was improved by introducing extended lymph node dissection, especially in the cases of stage III & IV cancer in which a combined pancreatico-splenectomy could lead to cure when associated with lymphadenectomy. In cases of a positive serosal exposure, the 5-year survival rate was increased by extended lymphadenectomy from 21% to 46% (p < 0.02). Anastomotic leakage occurred in 4.2%. The postoperative mortality rate was 1.6%, occurring in only 4 patients.

Adenocarcinoma↗
PubMed1994

Surgical management of gastric cancer patients with liver cirrhosis.

From 1966 to 1992, a total of 3,118 gastric cancer (GC) patients were referred to the First Department of Surgery, Kurume University Hospital. Fifty-six (0.02%) of these patients also had liver cirrhosis (LC). Forty-nine (87.5%) of these patients with LC underwent GC resection. Postoperative complications occurred in 32.7%, but the operative mortality rate was zero using our preoperative assessment of liver function to decide the operation. The 5-year survival rate following curative resection was 69% in early cancer and 17% in advanced cancer. Deaths were mainly cirrhosis-related in the early cancer cases, while cancer recurrence and hepatic failure were the main causes of mortality in the advanced cancer cases.

Female↗