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Biomedical subjects

O Igawa

Publications and source records attributed to O Igawa.

At least 37 records · Page 2Linked to original sources

Augmented exercise plasma noradrenaline with impaired chronotropic responsiveness in patients with hypertrophic cardiomyopathy.

1. There is controversy regarding plasma catecholamine levels in patients with hypertrophic cardiomyopathy (HCM) and few data exist on serial plasma catecholamine measurements during exercise. The present study determined whether cardiovascular and plasma catecholamine responses to exercise were altered in patients with HCM. 2. Plasma noradrenaline (NA) and adrenaline were measured at rest, at the end of each stage during exercise and immediately and 5 min after submaximal treadmill exercise in 15 patients with non-obstructive HCM (13 males, two females; mean (+/- SEM) age 54 +/- 3 years) and in 15 age- and sex-matched controls. The ratio of the increment in heart rate (HR) divided by the increment in plasma NA during exercise (delta HR/delta NA) was used as an index of chronotropic sympathetic responsiveness to exercise. 3. Exercise duration was shorter (11.2 +/- 0.6 vs 8.7 +/- 0.6 min for control vs HCM, respectively; P < 0.01) and diastolic blood pressure was significantly higher at stages I and II of modified Bruce protocol HCM. 4. Resting plasma NA levels (149 +/- 17 vs 167 +/- 28 pg/mL for control vs HCM, respectively; NS) were not different, but plasma NA levels at stages I and II were significantly higher in HCM than in controls (243 +/- 26 vs 399 +/- 69 pg/mL (P < 0.05) and 308 +/- 30 vs 548 +/- 110 pg/mL (P < 0.05), respectively). 5. Peak plasma NA levels were not significantly higher in HCM than in controls (578 +/- 59 vs 918 +/- 184 pg/mL, respectively; NS). 6. The ratio delta HR/delta NA was significantly lower in HCM compared with control at stages I and II (0.49 +/- 0.10 vs 0.21 +/- 0.05 (P < 0.05) and 0.38 +/- 0.06 vs 0.20 +/- 0.05 (P < 0.05), respectively). There were no differences in plasma adrenaline responses during exercise between the two groups. 7. Patients with HCM had augmented plasma NA levels during submaximal exercise with a higher diastolic blood pressure response. Chronotropic sympathetic responsiveness was impaired during the early stages of exercise in patients with HCM.

Adult↗

Idiopathic left ventricular tachycardia with block between purkinje potential and ventricular myocardium.

We performed radiofrequency current catheter ablation in a patient with idiopathic LV. While mapping the inferoapical LV septum during tachycardia, spontaneous termination of tachycardia was observed with block between Purkinje (P) potential and ventricular electrogram (P-V block). The cycle length of the tachycardia was associated with prolongation of P-P interval and P-V interval. P potential recording at this site was earliest and at very low amplitude during tachycardia. The radiofrequency current at this site was successful. These findings indicated that Purkinje fiber was a critical part of the tachycardia circuit. Ablation was successful at a site where both an earliest and low amplitude P potential was recorded during tachycardia, and where P-V block that was induced by catheter manipulation was observed during tachycardia.

Adult↗

Activation mapping from the coronary sinus may be limited by anatomic variations.

The purpose of this study was to examine the anatomic relationship between the mitral annulus (MA) and the coronary sinus (CS). Fifty consecutive hearts of 31 men and 19 women, 63.5 +/- 13.7 years of age, were examined at autopsy. MA was divided perpendicularly to the annular plane into an anteromedial block and a posterolateral block by sectioning from the CS ostium through the center of MA. The posterolateral block was subdivided radially into five equal sections at 36 degrees, 72 degrees, 108 degrees, 144 degrees, and 180 degrees. The distance from the ventricular endocardium under MA to the nearest wall of CS (D) was measured in each cross-section. D measured 9.7 +/- 2.3, 10.9 +/- 3.3, 10.2 +/- 3.6, 9.2 +/- 3.4, and 8.2 +/- 2.9 mm at 36 degrees, 72 degrees, 108 degrees, 144 degrees, and 180 degrees, respectively. D at 72 was significantly longer than at 144 degrees and 180 degrees (P < 0.01). Likewise, D at 108 degrees was significantly longer than at 144 degrees and 180 degrees (P < 0.05). The population was divided according to the morphology into five patterns. "Type C," the pattern that separated in the middle section and then reapproximated, was more common (66%) than any other pattern. D was confirmed to be longest at the level of the 72 degrees section, corresponding to a left posterolateral free-wall location. The potential mapping in CS would be easily modified by this anatomic feature. When mapping activation from the CS, the electrophysiological data should be interpreted in light of these anatomic findings.

Cadaver↗

Excess urate excretion correlates with severely acidic urine in patients with renal hypouricemia.

We evaluated the renal handling of urate in 12 Japanese renal hypouricemia patients, and studied the relationship between the renal handling of urate and the urinary pH. The patients were classified into the 4 subtypes of renal hypouricemia: (defective presecretory reabsorption (Pre), defective postsecretory reabsorption (Post), enhanced tubular secretion (Secretion), and defective presecretory and postsecretory reabsorption (Pre&Post) as based on a pharmacological test. Seven patients showed acid urine with a urinary pH of less than 5.9, although this was not accompanied by any abnormality of blood pH, partial pressure of carbon dioxide (PaCO2), or blood HCO3-. The urinary pH in the morning significantly correlated with the ratio of urate clearance to creatinine clearance in the morning, whereas the urinary urate concentration in the morning did not correlate with the urinary pH in the morning. In the Pre&Post patients, the urate excretion was higher and the urinary pH was more acidic compared to the other subtypes. The administration of K+-, Na+-citrate significantly alkalized the urinary pH in the patients with renal hypouricemia. These results suggest that the acidic urine was significantly related to the Pre&Post subtype of renal hypouricemia with the higher urate excretion, and that this subtype might be a risk factor for complications in renal hypouricemia. The alkalization of urine might be a useful treatment for the complication of renal hypouricemia.

Adult↗

Influence of extracellular H+ and Ca2+ on Ro 22-9194-induced block of sodium current in cardiac myocytes.

1. Ro 22-9194 reduced the Na current in ventricular myocytes in either a tonic block or phasic block manner. 2. Ro 22-9194 had a higher affinity to the inactivated state (Kdi = 10.3 microM) than to the rested state (Kdrest = 180 microM). 3. Extracellular acidification enhanced the tonic block but reduced the phasic block. 4. Elevation of extracellular Ca2+ inhibited the enhancing effects of extracellular acidification. 5. These findings suggest that Ro 22-9194 strongly inhibits Na+ channels of the ventricular myocytes of the diseased hearts, characterized by the depolarized cell membranes and by acid conditions.

Animals↗

Tonic block of the Na+ current in single atrial and ventricular guinea-pig myocytes, by a new antiarrhythmic drug, Ro 22-9194.

Ro 22-9194 reduced the Na+ current in the atrial myocytes as well as ventricular myocytes in a tonic block fashion. Ro 22-9194 had a higher affinity to the inactivated state Na+ channels (KdI = 3.3 microM in atrial myocytes, KdI = 10.3 microM in ventricular myocytes) than to those in the rested state (KdR = 91 microM in atrial myocytes, KdR = 180 microM in ventricular myocytes), which indicated that Ro 22-9194 had a higher affinity to the Na+ channels in atrial myocytes than in ventricular myocytes. Ro 22-9194 shifted the inactivation curve in the hyperpolarized direction in both atrial and ventricular myocytes. These findings suggest that Ro 22-9194 more strongly inhibited the Na+ channel of the atrial myocytes of the diseased hearts with the depolarized membranes potentials than the Na+ channels in ventricular myocytes.

Animals↗

Amitriptyline inhibits the G protein and K+ channel in the cloned thyroid cell line.

We have reported that thyroid K+ channel is activated by extracellular application of the thyroid-stimulating hormone (TSH) using single channel recording method performed on cloned normal rat thyroid cell (FRTL-5) membrane. Treatment of dibutyryladenosine cyclic monophosphate (Bt2 cAMP) also activated the TSH-dependent K+ channel. These findings indicate that the thyroid K+ channel is activated through the TSH-adenosine cyclic monophosphate (cAMP)-protein kinase A system. We examined the effects of amitriptyline on TSH-guanosine triphosphate binding protein (G protein)-adenylate cyclase-cAMP-K+ channel system in the cloned normal rat thyroid cell line FRTL-5. Amitriptyline inhibited the cAMP production induced by TSH. Amitriptyline also inhibited the cAMP production induced by cholera toxin, indicating that amitriptyline inhibited the thyroid G protein. Amitriptyline had no effect on TSH-receptor binding and cAMP production by forskolin (adenylate cyclase stimulator). Amitriptyline inhibited the K+ channel activation by cAMP, indicating that the suppressing mechanism is not the inhibition of TSH receptor or G protein but the direct suppression of K+ channel. It was concluded that amitriptyline inhibited the thyroid G protein and K+ channel.

Amitriptyline↗

Renal handling of urate in a patient with familial juvenile gouty nephropathy.

We encountered a case of familial juvenile gouty nephropathy (FJGN) with an autosomal dominant transmission pattern. Hyperuricemia in the propositus was caused by renal underexcretion of urate although his erythrocyte purine enzyme was normal. A renal biopsy specimen from the propositus showed interstitial fibrosis with tubular atrophy. On pyrazinamide and probenecid tests, the tubular secretion of urate selectively decreased without changes in either presecretory or postsecretory reabsorption of urate when his renal function was normal. Probenecid increased the urinary urate excretion and Cur/Ccr. The serum urate concentration was poorly controlled by allopurinol. When his renal function deteriorated, the uricosuric effects of both probenecid and benzbromarone were attenuated. However, the combined administration of probenecid with allopurinol decreased the serum urate concentration. These data suggest that the tubular secretion of urate is selectively impaired in FJGN and at the stage of renal failure, the combination of an uricosuric agent with allopurinol might be effective in treating hyperuricemia in FJGN.

Adolescent↗

Treatment of torsade de pointes with intravenous magnesium in idiopathic long QT syndrome.

A middle aged woman with idiopathic long QT syndrome was found to have repetitive ventricular tachycardia of the "torsade de pointes" type. The arrhythmia was resistant to mexiletine and lidocaine, but was controlled by intravenous magnesium sulfate (MgSO4). The recurrent attacks were abolished by a bolus of 2.0 g MgSO4, and extremely prolonged QTU interval was reduced by intravenous infusion of 5 mg/min MgSO4 for 36 h. This case shows the effectiveness of intravenous magnesium in controlling the attack of torsade de pointes in patients with idiopathic long QT syndrome.

Adult↗

Sympathetic nervous system response to dynamic exercise in complete AV block patients treated with AV synchronous pacing with fixed AV delay or with auto-AV delay.

To investigate the sympathetic nervous system (SNS) responses and circulatory responses to exercise in eight patients (five male and three female) with complete atrioventricular block (CAVB) treated with atrioventricular (AV) synchronous pacing, a symptom-limited, multistaged treadmill stress test was performed, and plasma norepinephrine (NE) and circulatory parameters were measured at rest, at peak exercise, and in the recovery period. The eight patients were tested using the fixed AV interval (150 or 156 msec). Their exercise tolerance was generally poor. In all measured points, plasma NE levels were significantly higher in the eight study patients than those in the 12 normal subjects (eight male and four female). Systolic blood pressure (SBP) of CAVB patients elevated significantly after exercise compared to that at peak exercise. Heart rate (HR) responses of CAVB patients were characterized by their poor increase at peak exercise. These results suggest that some latent cardiac dysfunction continues in the CAVB patients however satisfactorily the AV synchronous pacing might perform. AV synchronous pacing with three different kinds of auto-atrioventricular delay (auto-AVD) was applied to three of the eight patients. In each AVD mode, a treadmill stress test was performed repeatedly according to the same protocol. Plasma NE concentrations under the condition with fixed AVD at peak exercise increased compared to those under the other two conditions with auto-AVD. These findings suggest that AV synchronous pacing with auto-AVD was better than that with fixed AVD during exercise. Plasma NE response to exercise seems to be a useful indicator for evaluating the condition of patients treated with DDD pacemakers and their adaptation for cardiac function.

Aged↗

Effects of trimebutine maleate on electrical activities of isolated mammalian cardiac preparations.

The effects of trimebutine maleate on electrical activity in guinea-pig isolated papillary muscles and rabbit sino-atrial nodes have been studied by means of a standard microelectrode method. In papillary muscles, trimebutine (above 10 microM) decreased the maximum rate of rise (Vmax) and the action potential duration at 90% repolarization (APD90), whereas the resting potential was not significantly altered. As to a decrease in Vmax, trimebutine produced a negative shift of the curve relating Vmax to the resting potential along the voltage axis. Trimebutine also depressed the slow action potentials of papillary muscles produced by 27 mM K and 0.2 mM Ba. In spontaneously beating sino-atrial node preparations, trimebutine (above 10 microM) decreased the heart rate, Vmax and the rate of diastolic depolarization. These results indicate that trimebutine maleate possesses a depressant action on the electrical activities of the fast- and slow-response fibres of the heart mainly due to inhibitions of both fast Na+ and slow Ca2+ channels.

Action Potentials↗

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↗

Sequential changes in serum thyroglobulin, triiodothyronine, and thyroxine following partial thyroidectomy for nontoxic nodular goiter.

The sequential changes in serum thyroglobulin (Tg), thyroxine (T4), free thyroxine (FT4), triiodothyronine (T3) and thyrotropin (TSH) were evaluated in ten patients on whom partial thyroidectomy for nontoxic nodular goiter had been performed. These changes were compared with those in ten patients who underwent upper abdominal surgery (cholecystectomy) under similar anesthesia, and whose calorie and fluid intake was similar until at least 48 hours after surgery. In agreement with previous reports, marked elevations in serum Tg that reached peak concentration (660 to 1350 ng/mL) at one or two hours after the thyroid incision (mean +/- SD; 787 +/- 304.0 ng/mL and 839 +/- 345.7 ng/mL, respectively) were observed. On the other hand, the significant but minimal increases in serum T4 and FT4 were observed at 24 hours (P less than .001 and P less than .001, respectively), 48 hours (P less than .01 and P less than .001, respectively), and 72 hours (P less than .01 and P less than .01, respectively) after the thyroid incision compared with the level just prior to the thyroid incision. Similarly, serum T3 also increased significantly at 6 to 168 hours after the thyroid incision (P less than .01, P less than .05, P less than .05, P less than .05, and P less than .05, respectively). These increases in serum T4, FT4 and T3 were not observed in the cholecystectomy patients. The mean serum TSH levels at 24 to 72 hours after thyroid incision and those at 6 to 48 hours after the abdominal incision were significantly decreased compared with those before thyroid and abdominal incision, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

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↗

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↗