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Biomedical subjects

I Kodama

Publications and source records attributed to I Kodama.

At least 163 records · Page 9Linked to original sources
PubMed1991

A combination of inactivated sodium channel blockers causes competitive interaction on dV/dtmax of single ventricular myocytes.

STUDY OBJECTIVE: The aim was to study an interaction between class I antiarrhythmic drugs on the cardiac sodium channels. DESIGN: The single pipette, whole cell clamp method was employed to control and record membrane potential. The maximum upstroke velocity (dV/dtmax) was measured as an index of sodium channel availability during treatment of the preparations with aprindine (5 microM) in combination with mexiletine (40 microM), and lignocaine (40 microM). EXPERIMENTAL MATERIAL: Single ventricular myocytes (n = 6-8 per experiment) isolated from guinea pig hearts were used. MEASUREMENTS AND MAIN RESULTS: Trains of depolarisation to 0 mV (0.2-2.0 Hz) were applied from the resting membrane potential (-85 mV) following a long quiescent period to evaluate "tonic" and "use dependent" decrease (block) of dV/dtmax. Additional application of mexiletine or lignocaine to aprindine resulted in an increase of tonic block and a decrease of use dependent block. Because of such counteracting action, the steady state dV/dtmax during the train of depolarisation was unaffected for mexiletine, and even increased for lignocaine. Dual exponential components of dV/dtmax recovery following a 1 s conditioning depolarisation after admixture of mexiletine or lignocaine to aprindine suggest their competitive interaction on cardiac sodium channels. CONCLUSION: A combination of class I antiarrhythmic drugs having high affinity for the inactivated state of sodium channels may cause a reductive effect on dV/dtmax through competitive displacement from common receptors.

Animals↗
PubMed1991

Cytosolic calcium staircase in ventricular myocytes isolated from guinea pigs and rats.

STUDY OBJECTIVE: The aim was to study intracellular calcium dynamics underlying positive or negative tension staircase of mammalian hearts. DESIGN: Changes in cytosolic calcium concentration [( Ca2+]i) in single ventricular myocytes were investigated using a Ca2+ indicator, fura-2. Beat to beat alterations in fura-2 fluorescence and cell edge movement on resumption of stimulation were recorded on video tape, and analysed by a computer based image processing system. EXPERIMENTAL MATERIAL: Single ventricular myocytes were enzymatically isolated from the hearts of 30 adult guinea pigs and 25 adult rats. MEASUREMENTS AND MAIN RESULTS: In guinea pig ventricular myocytes, the positive contractile staircase was associated with ascending staircases of both peak systolic and end diastolic [Ca2+]i because of a cumulative increase in diastolic [Ca2+]i. In rat ventricular myocytes, the negative contractile staircase was accompanied by a descending staircase of peak systolic [Ca2+]i, while end diastolic [Ca2+]i level was unchanged due to the rapid decay of [Ca2+]i transients. Ryanodine (10 microM) reversed the mode of [Ca2+]i and contractile staircases from negative to positive in rat myocytes, whereas it caused minimal alteration in guinea pig myocytes. CONCLUSIONS: Tension staircase of mammalian hearts depends on diastolic Ca2+ level as well as Ca2+ handling by the sarcoplasmic reticulum. The positive staircase may require progressive increase in diastolic [Ca2+]i, while the negative staircase may be mediated by depletion of activator Ca2+ in the sarcoplasmic reticulum.

Animals↗
PubMed1991

Block of cardiac sodium channels by amiodarone studied by using Vmax of action potential in single ventricular myocytes.

1. Acute effects of amiodarone on cardiac sodium channels were investigated in ventricular myocytes isolated from guinea-pig hearts, and compared with those of lignocaine. 2. Transmembrane potential was recorded and controlled by whole-cell current-clamp and voltage-clamp respectively through suction pipette electrodes. The maximum upstroke velocity (Vmax) of the action potential was used as a qualitative index of sodium channel availability. 3. In myocytes treated with amiodarone (1 microM) or lignocaine (40 microM), Vmax of reference action potential elicited at 0.03 Hz was decreased by 6-11%, indicating minimal tonic block of sodium channels. 4. Application of a single conditioning depolarization to those myocytes resulted in a significant decrease in Vmax of a subsequent test action potential. The Vmax reduction was enhanced in a single exponential function as the clamp pulse duration was prolonged. Time constants at 0 mV clamp were 25 ms for amiodarone and 122 ms for lignocaine. 5. Vmax recovery of test action potential following a 1000 ms 0 mV clamp was approximated by a dual exponential function. Time constants for the late slow component (tau R) at the resting potential level were 418 ms for amiodarone and 178 ms for lignocaine. tau R values were shortened in a voltage-dependent manner by hyperpolarization during the coupling interval. 6. These findings suggested that amiodarone, like lignocaine, blocks the sodium channel primarily when it is in the inactivated state. Both onset and offset kinetics of the block are very rapid. Such sodium channel blocking characteristics may contribute to its potent antiarrhythmic activity.

Action Potentials↗
PubMed1991

Gastric cancer following gastrectomy for benign gastroduodenal disease.

Twenty-four cases of resected remnant cancers following partial gastrectomy were retrospectively investigated for benign gastroduodenal disease. The time interval between the initial gastrectomy and the remnant gastrectomy was more than 10 years in 19 (79%) patients and less than 10 years in 5 (21%) patients. There were 2 cases with remnant cancer at stage I, 1 at stage II, 3 at stage III and 13 at stage IV for the all cases with a time interval of more than 10 years. Early-type remnant gastric cancer has a frequency of only 5%. The proportion of positive lymph node metastases was high, in 84%.

Aged↗
PubMed1991

Gastric cancer invading the esophagus--improved management.

From 1978 to 1989, a total of 1272 patients with gastric cancer were admitted to Kurume University Hospital. Of these, 1184 (93%) underwent gastric resections. Of the resected cancers, 140 cases were gastric cancers invading the esophagus, as confirmed by postoperative pathological studies. For all 168 gastric cancers invading the esophagus, the resectability rate was 83% (140/168). These cancers were subdivided chronologically, with those during 1978-1983 included in Group 1 and those during 1984-1989 in Group 2. Group 2 patients were treated with a higher proportion of aggressive extended radical operations, such as combined resections of the diaphragm and lymph node dissections as far as the paraaortic lymph nodes (N4). The resectability rate was 76% in Group 1 and 93% in Group 2, due to the more aggressive operations. A lower esophagectomy with a total gastrectomy, mainly from a left thoracoabdominal approach, was performed for 71% of the patients in Group 1, and for 90% in Group 2. Lymph node metastasis was related to the extent of esophageal invasion and inversely related to the 5 year-survival rate. In all cases of esophageal invasion of less than 1 cm, there were no mediastinal lymph node metastases, and the 5 year-survival rate was 76%. On the other hand, when esophageal invasion was more than 4 cm, 50% had mediastinal lymph node metastases and the 5 year-survival rate was zero. The tumor size was also related to lymph node metastasis. When the maximal tumor length was less than 5 cm, a negative lymph node metastasis was found in 78% of cases, and the 5 year-survival rate was 76%.(ABSTRACT TRUNCATED AT 250 WORDS)

Esophageal Neoplasms↗
PubMed1991

Surgical management of adenocarcinoma in the gastric cardia.

From 1979 to 1988, a total of 1083 patients with gastric cancer underwent resection at Kurume University Hospital. Among these cancers, 183 (16.8%) were located in the upper third of the stomach. Of these, 56 (5.2%) were adenocarcinomas in the esophagogastric (E-G) junction. Cancer in this area was designated as cardia cancer when the focus of the cancer was macroscopically located within 2 cm of the E-G junction line and the tumor was less than 8 cm in diameter. The incidence of early gastric cancer in the cardia was only 13%, while the incidence for stage III advanced cancer was high at 46%, and the positive lymph node metastasis rate was 59%. Thirty-nine (70%) were cured by resection with a 5-year-survival rate of 64%, while for non-curative resection, this was only 10%. Twenty-two cases of either advanced cardia or advanced CE cancer underwent combined resection of the diaphragm. The rate of invisible metastasis to the diaphragm was 20% in our experimental study. The two year-survival rate for a combined resection of the diaphragm was 64%, while the rate for those who did not undergo a required combined resection was 42%.

Adenocarcinoma↗
PubMed1991

Detection of preoperatively unrecognized multiple pancreatic pseudocysts by intraoperative ultrasonography. Report of two cases.

During two pancreatic operations, intraoperative ultrasonography detected multiple pancreatic pseudocysts that were unrecognized preoperatively. In each operation, a single pseudocyst was detected by preoperative ultrasonography, computed tomography, and intraoperative surgical exploration. In addition, high-resolution ultrasonography used during the operations also identified and precisely localized additional smaller pseudocysts. Also, the use of color Doppler imaging during the operations enabled the delineation of small blood vessels around the pseudocysts. The accurate diagnosis of multiple pseudocysts and the precise anatomic information provided by intraoperative ultrasonography permitted appropriate surgical treatment of the pancreatic pseudocysts which, in turn, might help prevent recurrence of the disease.

Adult↗
PubMed1990

Two types of sodium channel block by class-I antiarrhythmic drugs studied by using Vmax of action potential in single ventricular myocytes.

The state-dependent sodium channel block by mexiletine, tocainide, lidocaine, OPC-88117, aprindine, quinidine, disopyramide and AN-132 was investigated in single ventricular myocytes isolated from guinea-pig hearts. A single conditioning clamp pulse with a duration from 10 ms to 1000 ms was applied from the resting potential (-82 mV) to 0 mV level using a suction pipette whole-cell voltage clamp technique, and the maximum upstroke velocity (Vmax) of a test action potential elicited 100 ms after termination of the clamp pulse was measured as an index of sodium channel availability. In myocytes treated with the eight drugs, such clamp pulse caused a significant decrease in Vmax. With mexiletine, tocainide, lidocaine, OPC-88117 and aprindine, the Vmax reduction was enhanced progressively as the clamp pulse duration was prolonged. With quinidine, disopyramide and AN-132, an appreciable Vmax reduction at the shortest clamp pulse was followed by an additional small enhancement of the Vmax decay. These findings suggest that the former group of drugs may block the sodium channel mainly during the inactivated state (inactivation blockers), whereas the latter one may do so mainly during the activated state (activation blockers). Multiple short clamp pulses caused a greater Vmax reduction than a single prolonged clamp pulse for the activation blockers, and vice-versa for the inactivation blockers. Molecular dimensions of the eight drugs, which were estimated by X-ray diffraction of crystals, did not satisfy a simple size criterion as proposed by Courtney (1988) to explain such different types of sodium channel block by Class-I drugs.

Action Potentials↗
PubMed1990

Combined application of class I antiarrhythmic drugs causes "additive", "reductive", or "synergistic" sodium channel block in cardiac muscles.

STUDY OBJECTIVE: The aim was to study the differences in cardiac sodium channel block among combinations of class I antiarrhythmic drugs. DESIGN: Conventional glass microelectrode techniques were used to record transmembrane action potentials and their maximum upstroke velocity (dV/dtmax) reflecting the sodium channel availability, during treatment of the preparations with mexiletine (20, 40 microM) in combination with aprindine (5 microM), disopyramide (40 microM), and flecainide (5 microM). EXPERIMENTAL MATERIAL: Guinea pig papillary muscles (n = 6.8 per experiment) were used for the study. MEASUREMENTS AND MAIN RESULTS: In preparations constantly stimulated at 1 Hz, a shortening of action potential duration by aprindine was further enhanced, while prolongation by disopyramide or flecainide was reduced, after additional application of mexiletine. Trains of stimuli (0.5-2.0 Hz) were applied following a long quiescent period to evaluate "tonic" and "use dependent" decrease (block) of dV/dtmax. Additional application of mexiletine to the other three drugs resulted in an enhancement of tonic block. Use dependent block by aprindine at 0.5-1.0 Hz was reduced by 8-9% after admixture of mexiletine, reflected in net increase in dV/dtmax at steady states (reductive effect). Dual exponential components of dV/dtmax recovery from use dependent block in presence of both drugs suggest their competitive interaction on a common receptor site associated with sodium channels. Use dependent block by flecainide at 0.5-2.0 Hz was increased (p less than 0.01) after admixture of mexiletine. Steady state dV/dtmax was therefore largely inhibited by the drug combination (synergistic effect). Use dependent block in the presence of both disopyramide and mexiletine was similar to that predicted from the algebraic sum of each treatment. CONCLUSION: Combined application of class I antiarrhythmic drugs causes not only additive but also reductive or synergistic effects on dV/dtmax through modulation of use dependent block.

Action Potentials↗
PubMed1990

Electrical effects of okadaic acid extracted from black sponge on rabbit sinus node.

1. Effects of okadaic acid on electrical responses and spontaneous activity in the dominant pacemaker cells of rabbit sinus node were investigated by use of microelectrode techniques. 2. Okadaic acid (10(-5) M to 4 x 10(-5) M) caused a shortening of cycle length of spontaneous firing (SPCL) accompanied by increases in both maximum upstroke velocity at phase 0 (Vmax) and amplitude of action potential. 3. All of the effects of okadaic acid were relatively well preserved in a low-Ca2+ medium (0.12 mM). Okadaic acid restored the spontaneous activity of sinus node pacemaker cells even in a Ca2(+)-deficient medium. 4. The effects of okadaic acid were markedly inhibited or abolished in a low Na+ medium (24 mM or 70 mM) and in the presence of a slow channel blocking agent, verapamil (10(-6) M). 5. In voltage-clamp experiments using a two-microelectrode technique, okadaic acid (10(-5) M) caused an increase in the slow inward current without affecting the outward current. At a higher concentration (4 x 10(-5) M), the drug increased the outward current. 6. These results indicate that okadaic acid causes an increase in spontaneous activity of sinus node pacemaker cells mediated by an enhancement of slow inward current (Isi) through verapamil-sensitive Ca2+ channels.

Action Potentials↗
PubMed1990

Electrophysiological effects of AFD-21 and AFD-19, new antiarrhythmic compounds on papillary muscles and single ventricular myocytes isolated from guinea-pig hearts.

1. The effects of AFD-21, a newly synthesized antiarrhythmic compound, and AFD-19, its active metabolite, on transmembrane action potentials were examined in right ventricular papillary muscles and single ventricular myocytes isolated from guinea-pig hearts. 2. In papillary muscles, AFD-21 10(-5) M caused a slight prolongation of action potential duration (APD), while AFD-19 above 10(-6) M shortened APD in a dose-dependent manner. 3. Both AFD-21 and AFD-19 above 10(-6) M caused a significant and dose-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential without affecting the resting membrane potential. 4. In the presence of AFD-21 or AFD-19, 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 frequencies. A time constant for the recovery of Vmax from the use-dependent block was 2.9 s for AFD-21 and 3.6s for AFD-19. 5. The curves relating membrane potential and Vmax were shifted by AFD-21 (10(-5) M), or AFD-19 (10(-5) M) to the direction of more negative potentials by 5.3 mV and 5.1 mV respectively. 6. In single ventricular myocytes treated with AFD-21 (10(-5) M) or AFD-19 (10(-5) M), 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 both AFD-21 and AFD-19 have use- and voltage-dependent inhibitory action on the sodium channel by binding to the channel during its inactivated state, and that the unbinding rate is comparable to that of Class I antiarrhythmic drugs with intermediate kinetics.

Action Potentials↗
PubMed1990

ATP directly affects junctional conductance between paired ventricular myocytes isolated from guinea pig heart.

Effects of ATP on junctional conductance (gj) were investigated in paired ventricular myocytes isolated from guinea pig hearts. One cell of the pair was voltage-clamped with a single-patch pipette, and gj was measured after the perforation of the nonjunctional membrane of the partner cell. The current-voltage relation of gj was linear between -30 and +30 mV. The control gj at 5.0 mM ATP in 88 pairs of cells ranged from 100 to 1,055 nS (average, 268 nS). ATP within the range from 0.1 to 5.0 mM increased gj in a dose-dependent manner. The Hill coefficient was 2.6, and the half-maximum effective concentration of ATP was 0.68 mM. Adenylylimidodiphosphate (2 mM) caused a transient increase in gj in the presence of 0.5 mM ATP, but forskolin (30 microM), cyclic AMP (50 microM), catalytic subunit of cyclic AMP-dependent protein kinase (1 microM), and ADP (10 mM) had no significant effect on gj. The temperature coefficient of gj in the presence of 5.0 mM ATP was 1.29. These findings suggest that gj in paired ventricular myocytes is directly regulated by ATP probably through a specific ligand-receptor interaction between ATP and gap junctional channel protein.

Adenosine Diphosphate↗
PubMed1990

Mechanisms of atrial natriuretic peptide (ANP) secretion by rat hearts perfused in vitro--Ca2(+)-dependent signal transduction for ANP release by mechanical stretch.

Effects of temperature, contraction frequency, and intraatrial pressure on immunoreactive ANP release were investigated in isolated rat hearts perfused in Langendorff or working mode. A reduction of temperature from 37 C to 27 degrees C caused a decrease of ANP release by 64% indicating its marked temperature-dependency (Q10 = 2.92). An increase of atrial contraction frequency from 300 to 500/min in Langendorff-perfused hearts did not cause a significant change in the ANP release. An elevation of left atrial filling pressure of working hearts from 8 to 18 and 28 cmH2O was associated with pressure-dependent, and reversible increase of the ANP release. This pressure-induced release of ANP was inhibited in a low calcium (50% Ca2+) medium or by nifedipine (10(-7) M). N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7, 10(-7)M), a potent calmodulin inhibitor, or ryanodine (10(-8)M) had similar inhibitory action against the pressure-induced increase of ANP release. These results indicate that ANP secretion is primarily regulated by mechanical stretch or distension of the atrial wall, while the atrial contraction frequency is less important as a physiological stimulus for the secretion. The stretch-induced ANP secretion may require an influx of calcium through the voltage-dependent Ca2+ channels. It was also suggested that Ca2+ release from the sarcoplasmic reticulum leading to an activation of calcium-calmodulin kinase may be included in the intracellular processes of ANP release by mechanical stretch.

Animals↗
PubMed1990

[Cardiotoxicity study of ME2303 with the interval intravenous injections to rats].

Cardiotoxic effects of ME2303 were studied upon interval intravenous administrations to rats in comparison with those of doxorubicin (ADR). ME2303 at two dose levels of 3 and 9 mg/kg/day or ADR at a dose levels of 3 mg/kg/day was injected once a week for 3 weeks to female Sprague-Dawley rats (SPF) of 5-weeks of age. ADR depressed body weight gain, decreased food intake and increased water intake. Microscopic observation on the myocardial tissues revealed that ADR caused necrosis and cell infiltration, edema and disarrangement of myofibrils in some of ADR-treated rats. On the other hand, ME2303 showed no significant effects except that some decrease of food intake was observed at a dose level 9 mg/kg/day. No changes in left ventricular functions were observed in perfused hearts isolated from ADR- or ME2303-treated rats. However, about 133 ng/g of ADR remained in the hearts even at 1 week after the final administration whereas ME2303 or its metabolites were not detected, suggesting that ADR may cause disturbance of ventricular function and more cardiomyopathy after a longer term than 1 week following the final administration. These results suggest that the cardiotoxicity of ME2303 is weaker than that of ADR in rats.

Animals↗
PubMed1989

Fluctuations of membrane potential in isolated single ventricular myocytes of guinea-pig upon resumption of oxidative phosphorylation.

Electrical and mechanical activities of guinea-pig single ventricular myocytes were investigated under conditions simulating hypoxia-reoxygenation. The localized movement of sarcomere was recorded simultaneously with membrane potential, and analyzed using microcomputer-based image processing. Exposure to 5 mM CN- caused progressive shortening of action potential duration and attenuation of twitch contraction. The myocytes became inexcitable about 30 to 70 min after the CN- treatment. On removal of CN-, the myocytes exhibited periodic miniature membrane depolarizations from the resting potential level (-95 mV). When depolarizations were smaller than 6 mV in amplitude and longer than 500 ms in duration, they were accompanied by localized sarcomere shortening like a propagating contractile wave (unifocal oscillation). Membrane depolarizations of larger amplitude and shorter duration were associated with a more uniform pattern of localized sarcomere shortening (multifocal oscillation). Trains of electrical stimuli applied during the washing out period caused transient augmentation of potential fluctuation and enhancement of synchronization of sarcomere shortening. These results suggest that non-uniform elevation of intracellular calcium concentration on the resumption of oxidative phosphorylation may initiate oscillatory fluctuations of membrane potential leading to abnormal spontaneous excitation.

Action Potentials↗