[Determination of oxypurine and its clinical implication].
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Chromatography, High Pressure Liquid↗
Biomedical subjects
H Kotake
Publications and source records attributed to H Kotake.
Differences in urate metabolism between normouricemia and hyperuricemia in coronary heart disease in man.
We examined hyperuricemia in patients with coronary heart disease. In 85 patients with coronary sclerosis confirmed by coronary angiography, the serum urate level (6.08 +/- 1.60 mg/dL) was not different from that in subjects with normal coronary arteries (6.47 +/- 1.69 mg/dL). The incidence of hyperuricemia in patients with coronary sclerosis was 26%, and was significantly correlated with diuretics, obesity and hypertriglyceridemia, but not with hypertension or hypercholesterolemia. To elucidate the mechanism of urate metabolism in coronary sclerosis, we separated coronary sclerosis patients without complicating factors into hyperuricemics and normouricemics, and studied urate metabolism in comparison with subjects with normal coronary arteries. We found that normouricemics with coronary sclerosis had decreases in the filtered urate load and urate clearance with a normal urate-creatinine clearance ratio. Hyperuricemics with coronary sclerosis had decreases in urate clearance and urate-creatinine clearance ratios, but the filtered urate load was similar to that in normouricemics. It is suggested that in coronary sclerosis patients, normouricemics had a low glomerular filtration of urate with normal tubular urate transport, whereas hyperuricemics had enhanced tubular reabsorption of urate without any difference of urate filtration from normouricemics.
Coronary Disease↗
Suppression of catecholamine-induced abnormal pacemaker activities by magnesium ion in guinea pig cardiac muscle cells.
The effect of magnesium ion on the abnormal pacemaker activity of guinea pig ventricular muscle cells depolarized by 27 mM K+ was studied. Isoproterenol produced a small depolarization in the resting membrane and elicited automatic repetitive action potentials at higher concentrations in the presence of 0.2 mM Ba2+. This model was used to assess the antiarrhythmic effect of magnesium ion on cardiac muscle cells. Isoproterenol concentrations needed for depolarization alone or for depolarization plus automatic activity were taken as a basis for evaluation. The responsiveness of muscle cells to isoproterenol was suppressed significantly by increasing the magnesium concentration. It is concluded that magnesium ion may have an antiarrhythmic effect on partially depolarized cardiac muscle cells.
Animals↗
Electrophysiological studies on the effects of mianserin, a tetracyclic antidepressant agent, on isolated guinea-pig papillary muscle.
We studied the effects of mianserin on the action potentials of papillary muscle from the guinea-pig. Mianserin (above 10 microM) reduced the maximum rate of the rise (Vmax) of the action potential, and shifted the Vmax-Em relationship to more negative potentials. The compound also depressed the slow action potentials of K+-depolarized papillary muscles. It is concluded that relatively high concentrations of mianserin had an inhibitory action on the electrophysiological properties of both the fast- and slow-response fibers of the heart.
Action Potentials↗
Comparative study of the block of Vmax by aprindine and quinidine in the guinea-pig heart muscle.
The depression of Vmax of the action potential in guinea-pig ventricular muscle by aprindine and quanidine was compared. Aprindine caused a more pronounced rate-dependent block (Kd = 10(-6) M at 3.3 Hz) than did quinidine (Kd = 1.6 X 10(-5) M at 3.3 Hz). Aprindine shifted the relationship between Vmax and resting potential to a more negative potential (mean 9.2 mV: 10 microM) than did quinidine (mean 5.7 mV: 10 microM). In addition, aprindine caused a more pronounced resting block (Kd = 1.3 X 10(-5) M) than quinidine (Kd = 8.6 X 10(-5) M). It is concluded that aprindine has a higher affinity for activated and/or inactivated and resting state channels than quinidine, making channels unavailable for conduction upon activation.
Action Potentials↗
The usefulness of exercise-induced QRS axis shift as a predictor of coronary artery disease.
The QRS axis of 101 patients with coronary artery disease (CAD) and 57 normal subjects without CAD who underwent coronary arteriograms were measured before and after exercise testing. There was no improvement in the sensitivity of positive axis shifts (15 degrees or greater) for CAD (18%) when compared to the value of positive ST depression (61%). However, the specificity of positive axis shifts for CAD was significantly increased (98%) when compared to the value of positive ST depression (77%). In addition, 39% of those patients with CAD (39 of 101) showed false negative ST depression, but 18% of these patients (7 of 39) showed a positive axis shift. In normal subjects 21% (12 of 57) showed false positive ST depression, but all of the 21% (12 of 12) showed negative axis shift. There was no significant difference in the increments of heart rate between positive ST depression, positive axis shift, and negative ST depression, negative axis shift. No statistical differences in the sensitivity of ST depression and an axis shift for one-, two- and three-vessel diseases were noted. The specificity of left-axis shift for the left anterior descending artery lesion was 98% and the specificity of right-axis shift for the right coronary artery and/or left circumflex artery lesion was 91%. Therefore, the axis shift response is no more sensitive for the detection of CAD than ST depression. However, when a positive axis shift is observed, one can predict two things: the CAD and the localization of the coronary stenosis.
Arrhythmias, Cardiac↗
Effects of pirmenol hydrochloride on the spontaneous action potentials and membrane current systems of rabbit sinoatrial node cells.
The electrophysiologic effects of pirmenol hydrochloride on rabbit sinoatrial node cells were examined and compared with those of several class I antiarrhythmic agents. At 1 microM, pirmenol decreased the heart rate and the rate of diastolic depolarization and increased the action potential duration at half-amplitude. Above 10 microM, the agent also decreased the maximum rate of rise (Vmax) and the action potential amplitude significantly. The order of the inhibitory potency on Vmax was apridine greater than 711389-S greater than pirmenol greater than mexiletine greater than tocainide. With respect to the current systems, pirmenol decreased the slow inward current (Isi) and the time-dependent potassium outward current (IK). The agent also prolonged the recovery time constant of Isi without any changes in the decay process of the tail current (IK). These findings suggest that pirmenol depresses the spontaneous discharge of the sinoatrial node through a decrease in Isi and Ik.
Action Potentials↗
Antiarrhythmic effects of alpha-adrenoceptor antagonists in guinea pig ventricular myocardium.
Antiarrhythmic effects of alpha-adrenoceptor antagonists were assessed in the reserpinized guinea pig ventricular myocardium. Both bunazosin (1 to 3 x 10(-7) M), a new alpha 1-adrenoceptor antagonist, and yohimbine (1 to 3 x 10(-7) M), another adrenoceptor antagonist, suppressed the transient depolarization and triggered activity induced by a train of rapid stimuli in the solution containing low potassium ion (K+), high calcium ion (Ca2+) and strophanthidin (1 to 5 x 10(-7) M). Bunazosin (3 x 10(-6) M) abolished the facilitatory effect of hypoxia on beta-adrenoceptor mediated abnormal automaticity. To clarify the mechanisms underlying the antiarrhythmic properties of alpha-adrenoceptor antagonists, their electrophysiologic effects on the fast and slow action potentials were investigated. Alpha-adrenoceptor antagonists (bunazosin, yohimbine and phentolamine) suppressed the slow response in a dose-related manner. The voltage-dependent block and use-dependent block of the maximal rate of rise (Vmax) of action potentials by bunazosin (10(-5) to 10(-4) M) and yohimbine (10(-6) to 10(-5) M) were studied. The analysis of the onset and recovery kinetics from the use-dependent block of drugs showed that both bunazosin and yohimbine act as slow kinetic drugs. It is concluded that alpha-adrenoceptor antagonists seem to have an antiarrhythmic effect through the inhibition of fast sodium ion (Na+) and slow Ca2+ currents of the cell membrane independently of blockade of myocardial alpha-adrenoceptors.
Action Potentials↗
Positive inotropic effect of growth hormone releasing factor in the guinea-pig cardiac muscles in vitro.
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Animals↗
Effects of amoxapine on electrophysiological properties of rabbit sinoatrial node.
The effects of amoxapine on membrane potentials and membrane currents of rabbit sinoatrial node were studied using the double microelectrode voltage clamp method. Amoxapine (greater than 1 mumol.litre-1) decreased the heart rate and the maximum rate of rise and the rate of diastolic depolarisation in a dose dependent manner. Above 3 mumol.litre-1, amoxapine also decreased the action potential amplitude and prolonged the action potential duration at half amplitude. These electrophysiological changes induced by amoxapine were relatively reduced in a high calcium medium (extracellular calcium concentration 4.0 mmol.litre-1). In voltage clamp experiments amoxapine depressed the slow inward current, the time dependent potassium current, and the hyperpolarisation activated inward current. The major effect, however, was considered to be a reduction of the slow inward current. It is concluded that amoxapine produced an inhibitory action on the electrical activity of sinoatrial node, and this action is mainly explained by an inhibition of calcium influx through the cell membrane.
Action Potentials↗
Inhibitory actions of amoxapine, a tricyclic antidepressant agent, on electrophysiological properties of mammalian isolated cardiac preparations.
1. The electrophysiological effects of amoxapine were examined in guinea-pig isolated papillary muscles and rabbit sinoatrial nodes using a conventional microelectrode technique. 2. In papillary muscles, amoxapine above 10 microM caused a dose-dependent decrease in the maximum upstroke velocity (Vmax) of the action potential and in the action potential amplitude (APA), whereas the action potential duration at 90% repolarization (APD90) was significantly prolonged. For a decrease in Vmax, amoxapine produced a negative shift of the curve relating Vmax to the resting potential (Em) along the voltage axis to more negative membrane potentials. 3. Amoxapine also decreased Vmax and the overshoot potential of K+-depolarized slow action potentials of papillary muscle preparations. 4. In spontaneously beating sinoatrial node preparations, amoxapine above 3 microM reduced the heart rate, Vmax, APA and the slope of phase 4 depolarization in a dose-dependent manner. 5. It was concluded that amoxapine exerts inhibitory actions on fast- and slow-response fibres of the heart and these actions can be mainly explained by inhibition of both fast Na+ and slow Ca2+ channels.
Action Potentials↗
Chronotropic effect of nizofenone fumarate in rabbit sino-atrial node in vitro.
1. The effects of nizofenone fumarate were studied on the membrane potentials and currents of rabbit sino-atrial node preparations by means of the double-microelectrode voltage clamp method. 2. In spontaneously firing pacemaker cells, nizofenone (above 1 microM) decreased the heart rate. Above 3 microM, nizofenone reduced the maximum upstroke velocity, the amplitude of the action potential and the slope of the phase 4 depolarization, and prolonged the action potential duration at 50% repolarization. 3. Under voltage clamp conditions, nizofenone decreased the slow inward current and the time-dependent potassium outward current in a dose-dependent manner. 4. These findings suggest that nizofenone exerts an inhibitory action on the automaticity of sinoatrial node preparations via effects on both inward and outward currents.
Action Potentials↗
Renal hypouricemia due to an isolated renal defect of urate transport.
A 22-year-old man was found to have low serum urate concentration (1.1-1.7 mg/dl). His urate clearance was markedly increased (26.9-35.5 ml/min) and was not decreased after administration of pyrazinamide, but was even more increased after administration of benzbromarone. No other renal tubular abnormalities were detected. The young man has one sister and two brothers. His sister also has hypouricemia and hyperuricosuria. We suggest that the present case had a genetically determined renal abnormality affecting tubular presecretory reabsorption of urate.
Adult↗
Inotropic effect of thyrotropin-releasing hormone on the guinea pig myocardium.
The inotropic effect of the physiological level of TRH on isolated guinea pig cardiac muscle was studied using a force transducer and standard microelectrode techniques. TRH increased the contractile force of muscles dose-dependently without changing the time course of contraction in normal Tyrode and a high K+ (27 mM) solution. The positive inotropic effect of TRH was associated with an augmentation of slow action potentials in high K+ solution and was reduced in the presence of diltiazem, verapamil, and manganese. TRH potentiated the response of contractile force to increasing extracellular Ca2+ concentration. The inotropic effect of TRH was suppressed by metoclopramide, phentolamine, and cimetidine, but was not affected by propranolol. TRH increased the contractile force even in the myocardium of reserpinized guinea pig. It is suggested that TRH has a positive inotropic effect at least partly due to an increase in the slow inward Ca2+ current.
Action Potentials↗
Effect of class I antiarrhythmic agents on slow Ca2+ channels of myocardial cells.
The effects of several class I antiarrhythmic drugs (aprindine, cibenzoline, disopyramide, mexiletine, lidocaine, tocainide and 711389-S) were studied on slow Ca2+ channels of rabbit sinus node cells using a double microelectrode voltage clamp technique. All these drugs decreased the heart rate, the maximum rate of rise (Vmax), the action potential amplitude and the slope of the phase 4 depolarization in spontaneously beating sinus node preparations. The order of inhibitory potency on the heart rate was: aprindine greater than 711389-S greater than cibenzoline greater than or equal to disopyramide greater than mexiletine greater than or equal to lidocaine greater than tocainide. On the current systems, these drugs decreased the slow inward current (Isi) and the time-dependent potassium current (Ik). However, the major effect was a reduction of Isi. These agents also exerted a frequency-dependent block of Isi. Furthermore, comparing the effects of class I antiarrhythmic agents on slow Ca2+ channels, the order of inhibitory effect on Vmax of sinus node cells was: aprindine greater than 711389-S greater than cibenzoline greater than or equal to disopyramide greater than mexiletine greater than lidocaine greater than tocainide. These electrophysiological observations suggest that class I antiarrhythmic drugs have a depressant effect on slow Ca2+ channels as well as fast Na+ channels of myocardial cells, and that so-called "slow" kinetic drugs may depress slow Ca2+ channels more strongly than "fast" kinetic drugs.
Animals↗
Two cases of coronary artery spasm induced by indocyanine green.
There is no evidence in the literature that coronary artery spasm is induced by indocyanine green (ICG). In the present report, we describe 2 cases who developed chest pain with transient ST elevation on electrocardiograms after intravenous administration of ICG.
Aged↗
Electrophysiological effects of maprotiline, a tetracyclic antidepressant agent, on isolated cardiac preparations.
We studied the effects of maprotiline, a tetracyclic antidepressant agent, on transmembrane potentials recorded from papillary muscles of guinea pigs and sinoatrial nodes of rabbits, using standard microelectrode techniques. Maprotiline (10-100 microM) produced dose-dependent decreases in the maximum rate of rise (Vmax) and action potential duration in papillary muscles, while the resting potential (Em) was not significantly affected. Maprotiline also shifted the Vmax-Em relation to more negative potentials. The slow action potentials of papillary muscles elicited by high [K+]o were also depressed by the drug application. In sinoatrial node cells, maprotiline (above 10 microM) reduced heart rate, Vmax, and action potential amplitude, and increased the action potential duration at half-amplitude. The slope of the phase 4 depolarization was decelerated by the drug. These results suggest that maprotiline depresses not only the fast inward sodium current but also the slow inward calcium current, and that relatively high concentrations of maprotiline exert an inhibitory effect on the electrical activity of the fast- and slow-response fibers of the hearts.
Action Potentials↗
Actions of flunarizine dihydrochloride on the electrical activity of isolated guinea-pig papillary muscle and rabbit sino-atrial node.
Effects of flunarizine on electrophysiological properties of isolated guinea-pig papillary muscles and rabbit sino-atrial nodes were examined using conventional microelectrode and double-microelectrode voltage clamp methods. Although flunarizine did not affect the maximum rate of rise of the action potential (Vmax) in fast response fibers, the compound depressed the slow action potentials of K+-depolarized papillary muscle (at above 10 microM) and reduced the automaticity of sino-atrial node (at above 3 microM). In voltage clamp experiments, flunarizine selectively suppressed the slow inward current of sino-atrial node specimens. It is concluded that relatively high concentrations of flunarizine directly modify the electrical activity of isolated mammalian myocardium via a suppression of Ca2+ influx through the cell membrane.
Action Potentials↗