Biomedical subjects

I Hisatome

Publications and source records attributed to I Hisatome.

At least 37 records · Page 2Linked to original sources

PubMed1999

Hypertensive left ventricular hypertrophy is linked to an enhanced catecholamine response to submaximal exercise.

BACKGROUND: The serial plasma catecholamine response to exercise has not been studied fully in relation to left ventricular hypertrophy (LVH) in patients with hypertension (HT). This study determined whether plasma catecholamine responses to exercise are altered in essential HT in the presence or absence of LVH. MATERIALS AND METHODS: Plasma noradrenaline (NA) and plasma adrenaline (A) were measured at rest, during and after treadmill exercise in 59 hypertensive subjects and 22 age-matched control subjects. Patients were divided into LVH(-) (n = 20) and LVH(+) (n = 39) stratified by left ventricular mass index [LVMI: control subjects, LVH(-), LVH(+): 114 +/- 4, 105 +/- 3, 151 +/- 3 g m-2]. RESULTS: Exercise time (9.9 +/- 0.6, 7.6 +/- 0.7, 7.3 +/- 0.6 min) was shorter in patients with HT. Both systolic and diastolic blood pressures were higher in patients with HT, and no difference was observed between LVH(-) and LVH(+) patients. Resting plasma NA was not different (157 +/- 16, 173 +/- 17, 167 +/- 14 pg mL-1), but plasma NA at stage I (300 +/- 30, 342 +/- 40, 469 +/- 40 pg mL-1) was higher in LVH(+) patients than in LVH(-) patients or control subjects. Plasma A response to exercise was similar among the three groups. There was a positive correlation (r = 0.38, P < 0.001) between LVMI and Deltaplasma NA at stage I in all subjects. CONCLUSIONS: Patients with essential HT with LVH had augmented plasma NA response during submaximal exercise, whereas patients without LVH did not exhibit this augmentation. The positive correlation between LVMI and Deltaplasma NA suggested a possible association between the degree of cardiac hypertrophy and sympathetic activation during exercise.

Epinephrine↗

PubMed1999

Effects of hypoxic exercise conditioning on work capacity, lactate, hypoxanthine and hormonal factors in men.

1. Hypoxanthine is a purine degradation product and exercise plasma hypoxanthine can be an index of ATP supply-demand imbalance during exercise. The present study determined the effects of hypoxic exercise conditioning on work capacity, blood lactate, plasma hypoxanthine and various neurohormonal factors. 2. Blood lactate, plasma hypoxanthine and neurohormonal factors (catecholamines, renin-angiotensin system activity and natriuretic peptides) were measured at rest and after maximal cardiopulmonary exercise testing (at sea level) both at pre- and post-hypoxic exercise conditioning in six males (40 +/- 2 years). The training protocol consisted of ergometer exercise twice weekly for 40 min in a hypobaric chamber (61.7-47.2 kPa) for 3 weeks. 3. Pulmonary function and haematological and echocardiographic parameters were not altered after hypoxic exercise conditioning. Work rate at peak exercise (264 +/- 10 vs 321 +/- 31 W; P = 0.10) tended to be increased and peak O2 pulse (15.0 +/- 1.0 vs 18.4 +/- 1.4 mL/beat; P < 0.05) increased after exercise conditioning. The double product during submaximal exercise decreased and systolic blood pressure at peak exercise increased after exercise conditioning. Resting and exercise neurohormonal factors were unchanged, except for reduced resting plasma adrenaline levels. Blood lactate at peak exercise (7.4 +/- 0.7 vs 4.8 +/- 0.5 mmol/L; P < 0.05) became lower and peak plasma hypoxanthine (43.2 +/- 5.7 vs 26.4 +/- 5.0 mumol/L; P < 0.1) tended to be decreased after exercise conditioning. 4. Hypoxic exercise conditioning tended to increase maximal power output with a decrease in exercise blood lactate and a trend towards a decrease in exercise plasma hypoxanthine. These data suggest that exercise conditioning under simulated altitude may improve ATP supply-demand imbalance during exercise with less anaerobiosis, which could contribute to enhanced endurance performance.

Adult↗

PubMed1999

Effects of amlodipine on native cardiac Na+ channels and cloned alpha-subunits of cardiac Na+ channels.

The inhibitory effects of amlodipine besilate (CAS 11470-99-6) on the native Na+ current (INa) and cloned human cardiac Na+ channel alpha subunit (hH1) were studied by whole cell patch clamp techniques. Amlodipine produced tonic block of INa in a concentration- and holding potential (HP)-dependent manner with hyperpolarization of H infinity. Amlodipine produced phasic blockade of INa, which was dependent on HP and pulse duration. Amlodipine produced tonic blockade of hH1 in a concentration-dependent manner with 1 : 1 stoichiometry, and phasic blockade of hH1 which was dependent on the pulse duration. Amlodipine blocked INa in a voltage- and frequency-dependent manner via affinity to the resting as well as inactivated conformations of the alpha subunit.

Algorithms↗

PubMed1999

Hemodynamic basis for the acute cardiac effects of troglitazone in isolated perfused rat hearts.

Troglitazone is a thiazolidinedione used for the treatment of NIDDM and potentially for other insulin-resistant disease states. Troglitazone has recently been shown to increase cardiac output and stroke volume in human subjects. These actions are thought to be mediated by the reduction of peripheral resistance, but a potential direct effect on cardiac function has not been studied. Therefore, we investigated the direct cardiac hemodynamic effects of troglitazone in isolated perfused rat hearts. Five groups of hearts were studied. Hearts were tested under isovolumetric contraction with a constant coronary flow, and troglitazone (0.2, 0.5, and 1.0 micromol) was administered by bolus injection. Peak isovolumetric left ventricular pressure (LVPmax), peak rate of rise of LVP (dP/dt(max)), and peak rate of fall of LVP (dP/dt(min)) were significantly increased 1 min after troglitazone administration in a dose-dependent manner, while the heart rate (HR) and coronary perfusion pressure (CPP) were significantly decreased (P < 0.05). HR was then fixed by pacing and/or CPP was fixed with nitroprusside to eliminate any effect of the two variables on the action of troglitazone. With constant HR and/or constant CPP, the effect of troglitazone on LVPmax, dP/dt(max), and dP/dt(min) was still unchanged. In addition, the positive inotropic, positive lusitropic, and negative chronotropic actions of troglitazone were not influenced even when hearts were pretreated with prazosin, propranolol, or nifedipine. In conclusion, troglitazone has direct positive inotropic, positive lusitropic, negative chronotropic, and coronary artery dilating effects. The inotropic and chronotropic actions of troglitazone are not mediated via adrenergic receptors or calcium channels. These findings have important clinical implications for diabetic patients with congestive heart failure.

Animals↗

PubMed1999

QRST integral analysis of body surface electrocardiographic mapping for assessing exercise-induced changes in the spatial distribution of local repolarization properties in patients with coronary artery disease and in patients with previous anterior infarction.

We studied resting, postexercise, difference (postexercise - rest) QRST isointegral maps, and the correlation coefficient between resting and postexercise maps. Study I Fifteen controls and 48 patients without previous myocardial infarction were studied. In coronary syndrome X group (n = 14), no patients showed an abnormally negative area on the postexercise map. In coronary ST depression group (n = 26), 12 patients (46%) showed an abnormally negative area on the postexercise map, and the correlation coefficient was low. Although all control, syndrome X, and coronary ST depression patients showed the global-downward type of difference map, coronary ST elevation patients (n = 8) showed the right-downward and left-upward type, right-upward and left-downward type, or reversed saddle type. Coronary ST depression is related to a globally marked decrease in local repolarization forces. Coronary ST elevation is associated with multidirectional changes in local repolarization forces. Study II Fifty-one patients with previous anterior infarction (29 with residual ischemia and 22 without) were studied. The incidence of the global-positive type of maps was increased and that of the saddle-type map was decreased from rest to postexercise in both groups. The global-upward type or right-downward and left-upward type of difference map was observed in both groups, but the reversed saddle type, right-upward and left-downward type, or global-downward type was observed in the residual ischemia group (34%, 24%, and 14%, respectively). Residual ischemia causes multidirectional changes or a global decrease in local repolarization forces. In both studies, multidirectional changes in local repolarization forces may be related to the vulnerability to ventricular arrhythmias.

Adult↗

PubMed1998

Differences in the electrophysiological response to I- and the inhibitory anions SCN- and ClO-4, studied in FRTL-5 cells.

The electrophysiological properties of the Na+/I- symporter (NIS) were examined in a cloned rat thyroid cell line (FRTL-5) using the whole-cell patch-clamp technique. When the holding potential was between -40 mV and -80 mV, 1 mM NaI and NaSCN induced an immediate inward current which was greater with SCN- than with I-. The reversal potential for I- and SCN- induced membrane currents was +50 mV. This is close to the value of +55 mV calculated by the Nernst equation for Na+. These results are consistent with I- and SCN- translocation via the NIS that is energized by the electrochemical gradient of Na+ and coupled to the transport of two or more Na+. There was no change in the membrane current recording with ClO-4 indicating that ClO-4 was either not transported into the cell, or the translocation was electroneutral. ClO-4 addition, however, did reverse the inward currents induced by I- or SCN-. These effects of I-, SCN- and ClO-4 on membrane currents reflect endogenous NIS activity since the responses duplicated those seen in CHO cells transfected with NIS. There were additional currents elicited by SCN- in FRTL-5 cells under certain conditions. For example at holding potentials of 0 and +30 mV, 1 mM SCN- produced an increasingly greater outward current. This outward current was transient. In addition, when SCN- was washed off the cells a transient inward current was detected. Unlike SCN-, 1-10 mM I- had no observable effect on the membrane current at holding potentials of 0 and +30 mV. The results indicate FRTL-5 cells may have a specific SCN- translocation system in addition to the SCN- translocation by the I- porter. Differences demonstrated in current response may explain some of the complicated influx and efflux properties of I-, SCN- and ClO-4 in thyroid cells.

Animals↗

PubMed1998

Effects of a new angiotensin-converting enzyme inhibitor, alacepril, on changes in neurohormonal factors and arterial baroreflex sensitivity in patients with congestive heart failure.

OBJECTIVE: Patients with heart failure have abnormal neurohormonal regulation during orthostatic stress, and abnormal arterial baroreflex function. This study investigated the effects of alacepril, a new angiotensin-converting enzyme inhibitor with sulfhydryls, on changes in neurohormonal factors during tilt and on the arterial baroreflex control of heart rate. METHODS: Plasma concentrations of noradrenaline, adrenaline, renin activity, angiotensin II, and atrial natriuretic peptide were measured at supine rest and after 30 degrees head-up tilt with measurements of central venous pressure and cardiac dimensions in seven patients with congestive heart failure (65 years, ejection fraction = 34%). Arterial baroreflex control of heart rate was assessed by phenylephrine bolus. The arterial baroreflex test was re-examined 3 h after oral alacepril (37.5 mg). The tilt and arterial baroreflex tests were repeated 12 weeks after alacepril treatment (50 mg x day(-1)). RESULTS: Heart rate, blood pressure, and neurohormonal factors did not differ before and after chronic alacepril, except for a trend toward an increase in renin activity (2.0 vs 4.9 ng x ml(-1) x h(-1)). Head-up tilt decreased central venous pressure (-2.5 mmHg) with a decrease in cardiac dimensions in the pre-alacepril phase. These changes were accompanied by increases in noradrenaline, adrenaline, and angiotensin II and a decrease in atrial natriuretic peptide. After chronic alacepril, the increase in noradrenaline during head-up tilt tended to be smaller (84 vs 30 pg x ml(-1)), with similar changes in central venous pressure (-3.4 mmHg) and cardiac dimensions. Both acute (3.6 vs 4.8 ms mmHg(-1)) and chronic (3.6 vs 6.7 ms mmHg(-1)) alacepril treatment was associated with a trend towards an increase in the arterial baroreflex control of heart rate. CONCLUSION: These results suggest that treatment with alacepril may cause a reduction of sympathetic activation during orthostatic stress and may enhance arterial baroreflex function in patients with mild to moderate heart failure.

Aged↗

PubMed1998

Effect of sulfhydryl oxidoreduction on permeability of cardiac tetrodotoxin-insensitive sodium channel.

Effects of sulfhydryl oxidizing and reducing agents on permeability of the tetrodotoxin (TTX)-insensitive Na-channel were investigated in guinea-pig ventricular myocytes using the whole-cell patch-clamp technique. Mercury chloride (HgCl2) at 1-100 microM irreversibly blocked Na+ currents with no significant changes in the gating kinetics. In contrast, the hydrophilic sulfhydryl oxidizing agent, thimerosal at 50-100 microM little affected Na+ permeation through the Na-channel. The Hg2+-induced block of Na+ current could be readily reversed by 1,4-dithiothreitol (DTT), an agent that reduces disulfide bonds. These results indicate that the formation of sulfur-Hg-sulfur bridge is essential for Hg2+ block. Pretreatment with DTT prevented the Hg2+ block of Na+ current, whereas Zn2+ and Cd2+ retained their abilities to block Na+ current after DTT treatment. An application of Zn2+ or Cd2+ resulted in the restoration of Hg2+ sensitivity of the DTT-treated channel. A conformational model for the Na-channel with multiple free sulfhydryl groups and native disulfide bonds could account for our experimental data regarding the effects of sulfhydryl modifying agents on the channel permeability. We conclude that the cardiac TTX-insensitive Na-channel contains functionally important free sulfhydryl groups and disulfide bonds which are accessible from the extracellular side by an aqueous pathway. These sulfhydryls would be capable of modulating the Na-channel permeability by affecting the conformation of channel pore region.

Algorithms↗

PubMed1998

Effects of spironolactone on exercise capacity and neurohormonal factors in patients with heart failure treated with loop diuretics and angiotensin-converting enzyme inhibitor.

1. Treatment with spironolactone is reported to be useful when combined with loop diuretics and an angiotensin-converting enzyme (ACE) inhibitor in severe congestive heart failure (CHF). However, the effects of the addition of spironolactone on exercise capacity and neurohormonal variables have not been demonstrated. This study determined the effects of additive spironolactone on exercise capacity and neurohormonal factors in patients with mild CHF. 2. Oxygen uptake (VO2), plasma norepinephrine (NE), renin activity (PRA), angiotensin II (AII), aldosterone (ALD), and atrial natriuretic peptide (ANP) were measured at rest and after peak exercise in nine patients with CHF (six idiopathic and three ischemic cardiomyopathy; New York Heart Association (NYHA) classes II and III) who were already taking furosemide (mean 29 +/- 5 mg/day) and enalapril (mean 4.7 +/- 0.8 mg/day). Studies were repeated after 16 weeks of treatment with additive single daily dose of 25 mg of spironolactone. In four of nine patients, the exercise test was repeated after a 4-weeks washout of spironolactone. 3. Treatment with spironolactone caused natriuresis, decreased cardiothoracic ratio in chest X-ray (before vs. after treatment: 53.7 +/- 1.2 vs. 50.7 +/- 1.4%, P < 0.01), and improved NYHA functional class. Peak VO2 (17.1 +/- 1.6 vs. 17.5 +/- 2.2 ml/min/kg, NS) and heart rate and blood pressure responses to exercise were not altered. Resting NE (215 +/- 41 vs. 492 +/- 85 pg/ml, P < 0.01) and resting PRA (8.2 +/- 2.3 vs. 16.2 +/- 4.1 ng/ml/hr, P < 0.01) as well as peak NE (1618 +/- 313 vs. 2712 +/- 374 pg/ml, P < 0.01) and peak PRA (12.8 +/- 3.2 vs. 28.1 +/- 11.8 ng/ml/hr, P = 0.17) were augmented after additive spironolactone. ALD and AII were insignificantly increased, and ANP was insignificantly decreased at peak exercise after spironolactone treatment. Spironolactone washout was associated with a trend of the neurohormones to return toward pretreatment values. 4. In conclusion, chronic additive treatment with spironolactone was associated with neurohormonal activation both at rest and during exercise without changing the exercise capacity of patients with mild CHF who were already on loop diuretics and ACE inhibitor therapy.

Adult↗

PubMed1998

Evaluation of changes in sympathetic nerve activity and heart rate in essential hypertensive patients induced by amlodipine and nifedipine.

OBJECTIVE: To compare the effects of amlodipine and nifedipine on heart rate and parameters of sympathetic nerve activity during the acute and chronic treatment periods in order to elucidate their influence on cardiovascular outcome. DESIGN: A randomized and single-blind study. METHODS: We performed 24 h ambulatory electrocardiography and blood pressure monitoring of 45 essential hypertensive inpatients. Plasma and urinary catecholamine levels were measured during the control (pretreatment) period, on the first day (acute period) and after 4 weeks (chronic period) of administration of amlodipine and of short-acting nifedipine or its slow-releasing formulation. The low-frequency and high-frequency power spectral densities and low-frequency: high-frequency ratio were obtained by heart rate power spectral analysis. RESULTS: Blood pressure was significantly and similarly reduced by administrations of amlodipine, short-acting nifedipine and slow-releasing nifedipine during the chronic period. The total QRS count per 24 h, which remained constant during the chronic period of administration of slow-releasing nifedipine and was increased by administration of nifedipine, was decreased by 2.8% by administration of amlodipine. Administration of amlodipine decreased the plasma and urinary norepinephrine levels during the chronic period, whereas the levels were significantly increased by administration of short-acting nifedipine and not changed by administration of slow-release nifedipine. Although low-frequency: high-frequency ratio was increased significantly by administration of short-acting nifedipine and slightly by administration of slow-releasing nifedipine, administration of amlodipine reduced it during the acute and chronic periods. CONCLUSIONS: Administration of amlodipine did not induce an increase in sympathetic nerve activity in essential hypertensive patients during the chronic period, suggesting that beneficial effects on essential hypertension can be expected after its long-term administration. Administration of slow-releasing nifedipine induces milder reflex sympathetic activation than does that of short-acting nifedipine.

Adult↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

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↗

PubMed1998

Control of AMP deaminase 1 binding to myosin heavy chain.

AMP deaminase (AMPD) plays a central role in preserving the adenylate energy charge in myocytes following exercise and in producing intermediates for the citric acid cycle in muscle. Prior studies have demonstrated that AMPD1 binds to myosin heavy chain (MHC) in vitro; binding to the myofibril varies with the state of muscle contraction in vivo, and binding of AMPD1 to MHC is required for activation of this enzyme in myocytes. The present study has identified three domains in AMPD1 that influence binding of this enzyme to MHC using a cotransfection model that permits assessment of mutations introduced into the AMPD1 peptide. One domain that encompasses residues 178-333 of this 727-amino acid peptide is essential for binding of AMPD1 to MHC. This region of AMPD1 shares sequence similarity with several regions of titin, another MHC binding protein. Two additional domains regulate binding of this peptide to MHC in response to intracellular and extracellular signals. A nucleotide binding site, which is located at residues 660-674, controls binding of AMPD1 to MHC in response to changes in intracellular ATP concentration. Deletion analyses demonstrate that the amino-terminal 65 residues of AMPD1 play a critical role in modulating the sensitivity to ATP-induced inhibition of MHC binding. Alternative splicing of the AMPD1 gene product, which alters the sequence of residues 8-12, produces two AMPD1 isoforms that exhibit different MHC binding properties in the presence of ATP. These findings are discussed in the context of the various roles proposed for AMPD in energy production in the myocyte.

AMP Deaminase↗

PubMed1998

Sympathetic nervous response relative to the adenosine triphosphate supply-demand imbalance during exercise is augmented in patients with heart failure.

OBJECTIVE: Increase in plasma hypoxanthine (HX) (purine nucleotide degradation product from working muscle) reflects insufficiency of adenosine triphosphate (ATP) supply during exercise, and the exercise-induced increase in plasma norepinephrine (NE) can be an index of sympathetic nerve activity. The aim of this study was to investigate the relationship between plasma NE and plasma HX during exercise in patients with heart failure (HF) according to its severity. METHODS: Blood lactate, plasma HX, and plasma NE were measured at rest and after symptom-limited cardiopulmonary exercise test in 54 patients with HF (New York Heart Association [NYHA] classes I:18, II:20, III:16) and 19 normal subjects. RESULTS: Peak work rate and peak oxygen uptake decreased as the NYHA functional class increased. Blood lactate and plasma HX levels at rest were comparable, but peak blood lactate (normal, NYHA I, II, III: 6.4+/-0.3, 5.6+/-0.4, 5.3+/-0.3, 3.5+/-0.2 mmol/L) and peak plasma HX (3.6+/-0.4, 3.0+/-0.5, 2.4+/-0.3, 1.4+/-0.1 micromol/L) were progressively smaller as HF worsened. Resting plasma NE (137+/-15, 180+/-29, 201+/-21, 318+/-55 pg/mL) was significantly higher in NYHA class III HF, but peak plasma NE (2,235+/-356, 2,021+/-326, 2,188+/-292, 2,210+/-316 pg/mL) was not different among groups. The ratio of the exercise increments in plasma NE to the increments in plasma HX during exercise (deltaplasma NE/deltaplasma HX: 666+/-96, 1,083+/-229, 1,252+/-222, 2,260+/-351) increased according to the severity of HF. CONCLUSION: These data suggest that plasma levels of HX after maximal exercise are smaller as HF worsened, and sympathetic responsiveness to the imbalance of ATP supply-demand during exercise is augmented according to the severity of HF.

Adenosine Diphosphate↗

PubMed1998

Hematuria in patients with renal hypouricemia.

The characteristics of urate metabolism in renal hypouricemic patients with hematuria were studied to clarify the risk factors for hematuria in patients with renal hypouricemia. In 16 Japanese patients with isolated renal hypouricemia, urate metabolism was measured using the urate clearance study and the subtype of renal hypouricemia [defective presecretory reabsorption (Pre), defective postsecretory reabsorption (Post), enhanced tubular secretion (Secretion) and defective presecretory and postsecretory reabsorption (Pre&Post)] were determined by the pharmacological tests. Hematuria was seen in 7 out of the 16 patients (44%), all of whom were females (58%). Serum urate and urinary urate concentrations were significantly higher in the group with hematuria (Sur = 1.76 +/- 0.31 mg/dl and Uur/Ucr = 0.75 +/- 0.12: p<0.05) than in the group without hematuria (Sur = 1.44 +/- 0.46 mg/dl and Uur/Ucr = 0.56 +/- 0.04), although there was no difference in the urate excretion rate between the two groups. Hematuria was more likely to be accompanied by Post (75%) and Secretion (75%), which showed significantly higher urinary urate concentration (Uur/Ucr = 0.75 +/- 0.1 and 0.69 +/- 0.13, respectively) than by Pre (25%) and Pre&Post (0%), which showed lower urinary urate concentration (0.61 +/- 0.06 and 0.62 +/- 0.05, respectively). The risk factors for hematuria in patients with renal hypouricemia are the elevation of urinary urate concentration and the subtypes of Post and Secretion.

Adult↗

PubMed1998

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↗

PubMed1998

Expression of Shaker-type voltage-gated potassium channel genes in the guinea-pig.

Few potassium channel genes have been isolated in the guinea-pig despite detailed electrophysiological characterization of potassium channels in the guinea-pig heart. We obtained partial clones of Shaker-type potassium channel genes in the guinea-pig and demonstrated their tissue distribution. Partial clones of the Shaker-type potassium channel genes were obtained by RT-PCR or genomic PCR. mRNA expression was measured by RNase protection assays in the heart, brain, and skeletal muscle. Three of the five obtained channel genes were expressed in the guinea-pig heart; Kv1.2, Kv1.3, and Kv1.6. Kv 1.6 expression was markedly at a higher level in the atrium than in the ventricle. Expression of the channel genes in the guinea-pig was different from that in human and rat, which may contribute to the species-specific action potential waveform.

Animals↗