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Biomedical subjects

H Kotake

Publications and source records attributed to H Kotake.

At least 109 records · Page 6Linked to original sources

Effect of pinacidil on the electrophysiological properties in guinea-pig papillary muscle and rabbit sino-atrial node.

The electrophysiological effect of the antihypertensive drug pinacidil has been examined in preparations of guinea-pig papillary muscle and rabbit sino-atrial node using a standard microelectrode method. In papillary muscle preparations, pinacidil (greater than 30 microM) shortened the action potential duration (APD), whereas it did not affect the maximum rate of rise (Vmax). Pinacidil (greater than 1 microM) also decreased APD of slow action potentials evoked by high K+ (27 mM) solution containing 0.2 mM Ba2+. At 30 microM, the drug reduced the Vmax of slow action potentials. In the spontaneously beating sino-atrial node, pinacidil (greater than 30 microM) shortened APD. At 100 microM, it also decreased the heart rate, Vmax, action potential amplitude and the rate of diastolic depolarization. It is concluded that pinacidil modifies the electrical activity of myocardial cells probably due to an increase in the potassium conductance although in high concentrations the compound might also reduce Ca2+ influx through the cell membrane, which would contribute to an obvious negative chronotropic action.

Action Potentials↗

Excess purine degradation caused by an imbalance in the supply of adenosine triphosphate in patients with congestive heart failure.

To evaluate purine degradation in patients with congestive heart failure concentrations of serum hypoxanthine, lactate, and noradrenaline were measured before and after submaximal treadmill exercise in 12 patients with chronic congestive heart failure and nine healthy volunteers. In four patients the concentration of hypoxanthine was significantly higher than in the controls or in the remaining eight patients with congestive heart failure. Venous lactate and noradrenaline in the four patients with high concentrations of hypoxanthine were also significantly higher than those in the eight patients with normal concentrations of hypoxanthine. Patients who responded normally were also more likely to have been treated with vasodilators and angiotensin converting enzyme inhibitors. Exercise induced arrhythmias were more common in the patients with high concentrations of hypoxanthine. These results suggest that the excess purine degradation in patients with congestive heart failure might be the result of a "relative" disturbance in the supply of adenosine triphosphate caused by the shift of cellular metabolism from aerobic glycolysis to anaerobic glycolysis during submaximal exercise and that hypoxanthine (a substrate for xanthine oxidase and a source of free radicals) was increased after submaximal exercise in some patients with congestive heart failure.

Adenosine Triphosphate↗

Diagnostic value of R-wave amplitude increase during treadmill exercise testing for detecting coronary artery disease.

To evaluate the diagnostic value of an exercise-induced increase in R-wave amplitude (RWA) for detecting coronary artery disease (CAD), treadmill testing using the modified Bruce protocol was performed on a CASE II computerized system (Marquette) in 10 healthy young men, 35 patients (pts) with CAD, 22 subjects with normal coronary arteries, and 11 pts with aortic or mitral regurgitation. Based on the analysis of the patterns of serial changes in RWA in lead V5, we proposed new RWA criteria for detecting CAD. (1) During exercise, RWA increases in stage 1 and subsequently increases further or remains unchanged. (2) During exercise, RWA decreases in the early phase of exercise and subsequently increases. (3) In the recovery period, RWA shows a gradual and excessive increase. A combination of the above RWA criteria showed a sensitivity, specificity and accuracy of an equal value of 86%. We conclude that an exercise-induced RWA increase is a useful indicator for detecting CAD, especially when taking the patterns of serial changes into consideration, and that the abnormal RWA increase may be related to an increase in left ventricular (LV) end-diastolic volume due to exercise-induced LV dysfunction.

Adult↗

A case of secundum atrial septal defect combined with aortic stenosis and coronary artery disease showing a single second heart sound.

We describe an extremely rare case of secundum atrial septal defect with aortic stenosis and coronary artery disease showing a single second heart sound throughout the respiratory cycle by echocardiogram with simultaneous phonocardiogram. Aortic valve closure corresponded to the single second heart sound. We were unable to detect pulmonary valve closure (PVC) on echocardiogram. Because of the presence of pulmonary hypertension, the pulmonary component of the second heart sound (P2) was presumed to be increased in intensity, and the PVC-P2 interval was thought to be abbreviated. Carotid pulse tracing showed a prolongation of the left ventricular ejection time. We concluded that the single second heart sound was due to both prolongation of left ventricular systole and pulmonary hypertension.

Aortic Valve Stenosis↗

Appearance of multidisperse low density lipoprotein and altered lipoprotein composition in non-insulin-dependent diabetes with type IIa hyperlipoproteinemia.

The purpose of the present study is to elucidate the characteristics of lipoprotein disorders in diabetes mellitus. By analytical ultracentrifugation, non-insulin-dependent diabetic patients (NIDDM) with type IIa hyperlipoproteinemia (HLP) showed significantly higher incidence of multidisperse low density lipoprotein (LDL) than non-diabetics with type IIa HLP. Furthermore, LDL multidispersity in diabetic subjects seemed to be directly related to neither triglyceride (TG) levels in very low density lipoprotein (VLDL) nor the degree of glycemic control. Diabetics with multidisperse LDL had a lipoprotein profile that was different from the subjects with paucidisperse LDL as follows: (1) enrichment in the cholesterol content of VLDL, (2) TG-rich LDL with small flotation coefficient, (3) low cholesterol levels in high density lipoprotein2 along with enrichment in TG, and (4) high plasma concentrations of apoprotein B. Although the underlying mechanism behind the prevalence of multidisperse LDL in NIDDM with type IIa HLP remains unknown, it seems important that lipoprotein disorders in diabetics with multidisperse LDL were potentially atherogenic.

Aged↗

Effect of luteinizing hormone-releasing hormone on the mechanical activity of the guinea-pig cardiac muscle.

1. The inotropic effect of physiological concentrations of luteinizing hormone-releasing hormone (LH-RH) in isolated guinea-pig cardiac muscles was studied. 2. LH-RH increased the contractile force elicited by either fast and slow responses in a dose-dependent manner. 3. These effects of LH-RH were affected by phentolamine and diltiazem but not by propranolol and cold condition. 4. This study showed the positive inotropic effect of LH-RH on myocardium through the affection to intracellular Ca, and the difference from the effect of cardiotonic steroids.

Animals↗

Significance of coronary artery tone in patients with vasospastic angina.

To investigate the relation between basal coronary artery diameter and development of coronary artery spasm, the diameters of the proximal, middle and distal segments of the three major coronary artery branches, together with that of the left main trunk, were measured on a control angiogram and after ergonovine and nitrate administration in 30 patients with vasospastic angina without significant organic stenosis, and in 35 patients without ischemic heart disease. The percent change in coronary diameter after ergonovine and nitrate administration compared with the control diameter was used as an index of coronary vasoreactivity. In patients with vasospastic angina, coronary artery responses to both ergonovine and nitrate were greater in the spastic segments than in the other segments (p less than 0.05), and those of the coronary arteries without spasm were greater than those of the coronary arteries in patients without ischemic heart disease (p less than 0.01). There were no significant differences between the coronary artery diameters in the two groups after nitrate administration, and the control diameters were less in patients with vasospastic angina than in patients without ischemic heart disease. These observations indicate that a coronary vasomotion disorder, which involves increased basal coronary artery tone and hypersensitivity to vasoconstrictive stimuli, not only at a localized segment but also in the entire coronary artery tree, is present in patients with vasospastic angina. Clinically, evaluation of basal coronary artery tone may be useful for predicting the occurrence and location of coronary artery spasm.

Adult↗

Hypouricaemia with acute viral hepatitis.

We report five female cases of hypouricaemia accompanied by acute viral hepatitis (serum urate 101 +/- 12 mumol/l, mean +/- SD). Their urate clearance was increased to 14.2 +/- 3.4 ml/min during hyperbilirubinaemia but 24-h urate excretion was not elevated (2.09 +/- 0.64 mmol/24 h). No other renal tubular abnormalities were detected. Comparing urate metabolism with that of four cases of inborn renal hypouricaemia, the degree of uricosuria was lower. One patient showed elevation of serum and urinary oxypurine, which normalized with return of a normal blood uric acid level. In all cases, the serum urate returned to normal after improvement of liver function. We suggest that renal uricosuria due to an isolated renal defect of urate transport might contribute to hypouricaemia in these cases but that inhibition of xanthine oxidase activity might also contribute to this phenomenon.

Acute Disease↗

Effect of bile acid on electrophysiological properties of rabbit sino-atrial node in vitro.

1 In order to examine the action of bile acid on cardiac pacemaker activity, the effect of sodium taurocholate (NTC) was studied on the membrane potential and current of rabbit sino-atrial node preparations by means of a double microelectrode voltage clamp technique. 2 In spontaneously beating sino-atrial node preparations, NTC (above 30 microM) decreased the maximum rate of rise of the action potential. Above 100 microM, the compound also exerted a bradycardiac effect and decreased the rate of diastolic depolarization significantly. 3 On the current systems, NTC produced dose-related decreases in the slow inward Ca2+ current and the time-dependent outward K+ current. 4 It is concluded that NTC depresses the spontaneous discharge of the sino-atrial node through decreases in both inward and outward current systems.

Animals↗

Membrane actions of ethanol on rabbit sino-atrial node studied by voltage clamp method.

Electrophysiological effects of ethanol on rabbit sino-atrial node were studied by means of the double-microelectrode voltage clamp method. In spontaneously beating preparations, ethanol (above 1%) decreased the maximum rate of depolarization of the action potential. Furthermore, 3% ethanol produced a significant decrease in the action potential amplitude, the action potential duration at 50% repolarization and the rate of the diastolic depolarization. Of the current systems, voltage clamp studies showed that ethanol reduced the slow inward current, the time-dependent potassium outward current and the hyperpolarization activated inward current. These observations indicate that ethanol does not have an effect on a single current system, but directly modifies the spontaneous discharge of sino-atrial node pacemaker cells due to a reduction of the time-dependent current systems.

Action Potentials↗

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↗

Effects of ketanserin on the pacemaker activity of rabbit sinus node in vitro.

Electrophysiological effects of ketanserin on pacemaker activity of rabbit sinus node cells were studied using double-microelectrode voltage clamp method. Ketanserin (10(-5) mol/l) caused an increase in spontaneous cycle length accompanied by decreases in the maximum upstroke velocity of the action potential, the slope of the phase 4 depolarization and the action potential amplitude. On the current systems, ketanserin reduced the slow inward current (Isi) and the time-dependent potassium outward current (IK) in a dose-dependent manner. As for a decrease in the outward current, the agent did not change the steady-state activation of IK. These observations indicate that ketanserin does not have a specific effect on a single current system, but that the drug exerts an inhibitory effect on the electrical activity of the sinus node pacemaker cells.

Action Potentials↗

Transient QRS axis shift to the right during right coronary artery and/or left circumflex artery spasms.

The QRS axis was measured in 24 patients during ergonovine malate provocation test (EM test). Of 12 patients with significant spasm of the right coronary artery (RCA) and/or left circumflex artery (LCX), the QRS axis shifted to the right in 7 patients after the EM test (mean 8.2 degrees), and the axis shifted back to the left in 9 patients after nitroglycerin administration (mean -9.1 degrees). The sensitivity of right axis shift for RCA and LCX spasm was 58% and the specificity was 80%. Thus, right axis shift seems to be associated with myocardial ischemia due to RCA and LCX spasm and to be useful for the detection of RCA and/or LCX spasms.

Coronary Vasospasm↗

Cause of persistent hypouricemia in outpatients.

We measured serum urate in 3,258 Japanese outpatients. Five of them had persistent hypouricemia. Three also had microhematuria. Four of the five patients were proven to have renal uricosuria with hypouricemia, but otherwise normal tubular function. When tested with both pyrazinamide and benzbromarone, 1 patient had a presecretory reabsorption defect, 2 had postabsorption defects, and 1 an enhanced renal tubular secretion of urate. These results suggest that persistent hypouricemia in outpatients is of very low incidence, is usually caused by an isolated metabolic error of urate transport, and is not related to drug ingestion or systemic disease.

Benzbromarone↗

A case of paroxysmal ventricular tachycardia during pregnancy.

We report a case of a 37-year-old woman who had paroxysmal ventricular tachycardia (VT) during early pregnancy. She had severe hyperemesis, palpitation at 6 weeks of gestation and many episodes of paroxysmal VT, but no apparent organic heart disease. At that time she had a transient increase of thyroid hormone levels. With bed rest and without medication, her symptoms and episodes of VT disappeared in accordance with the improvement of hyperemesis and thyrotoxicosis. She demonstrated a rare course of arrhythmias in which the deterioration of VT was observed at transient thyrotoxicosis and hyperemesis.

Adult↗

Effect of taurine administration on serum lipid and biliary lipid composition in man.

The effect of oral administration of taurine (3.2 g/day, 2 weeks) on the metabolism of lipids and bile acids was studied with healthy humans. Four male subjects were fed taurine. Another five male subjects were administered 1 g of cholesterol daily for two weeks and, at intervals of two weeks, cholesterol and taurine simultaneously. Serum lipoprotein and duodenal bile were analyzed. Oral administration of taurine resulted in the increase of taurine-conjugated bile acids. However, neither serum lipid nor biliary lipid composition was altered. Addition of taurine with cholesterol administration showed elevation of both the serum low density lipoprotein cholesterol level and the lithogenic index in bile. The ratio of glycine-to taurine-conjugated bile acids was changed from 4.1 to 0.63. The ratio of cholic acid/chenodeoxycholic acid was augmented from 0.57 to 0.81. The percentage of taurocholic acid, taurochenodexycholic acid and taurodeoxycholic acid were increased about 4-fold, 2.5-fold and 3-fold, respectively. Our results suggested that taurine administration alone did not influence the serum lipid level although taurine-conjugated bile acids were increased. The taurine intake would increase serum low density lipoprotein cholesterol and biliary cholesterol levels when excessive cholesterol is administered simultaneously.

Administration, Oral↗

[Sympathetic nervous system response to exercise in patients with congestive heart failure].

The response of the sympathetic nervous system to exercise in patients with congestive heart failure was studied in 65 patients (NYHA functional class I 28, II 23, and III 14) and 22 normal subjects (N) by submaximal treadmill testing with the modified Bruce's or Sheffield's protocols. Plasma norepinephrine (NE) and epinephrine (E) levels were also measured at rest, at the end of each stage, and immediately after and 5 min after exercise. In accordance with the severity by NYHA functional class, the exercise duration became shorter and the discontinuation of exercise with symptoms occurred more frequently. Systolic blood pressure and double products (DP) at the peak exercise were significantly lower in patients with NYHA class III. NE and increments of NE increased during exercise [peak NE (pg/ml); N: 589, I: 646, II: 1253, and III: 997] and were higher at rest, during exercise and in recovery in patients with NYHA classes II and III than in the normal subjects and NYHA class I patients. E increased gradually during exercise [peak E (pg/ml); N: 60, I: 66, II: 63, and III: 66] and there were no significant differences among the four groups. A negative correlation (r = -0.53) between the peak NE and exercise duration was observed in normal subjects, while a positive correlation (r = 0.55) was observed in patients with NYHA class II. A positive correlation (r = 0.54) between DP at the peak exercise and the peak NE was observed in patients with NYHA class I, whereas a negative correlation (r = -0.46) was observed in patients with NYHA class III. The NE response in patients with NYHA classes II and III increased significantly, suggesting compensatory activation of the sympathetic nervous system for impaired cardiac function. In conclusion, the NE response to submaximal exercise testing differs in each NYHA functional class and it might be a useful indicator to evaluate cardiac function of patients with congestive heart failure.

Aged↗