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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this study was to compare the myocardial oxygen cost of augmented inotropic state produced by ouabain, norepinephrine, or increased heart rate. This problem was examined in dogs using an isovolumically contracting left ventricular preparation. Inotropic state was measured as the maximum observed contractile element velocity at the lowest common level of wall stress (MAX V). Peak left ventricular wall stress was maintained constant in each dog so that it would not influence changes in myocardial oxygen consumption (MVO2). Ouabain (4 X 10(-2) mumoles/Kg.) and norepinephrine (2 X 10(-3) mumoles/Kg./minute) always augmented inotropic state (MAX V) and increased MVO2. The positive slopes of the regression of MVO2 on MAX V for ouabain (45.4 +/- 12.5 microliter/beat/100 Gm./muscle length/sec; mean +/- SEM) and norepinephrine (34.5 +/- 5.6 microliter/beat/100 Gm./muscle length/sec; mean +/- SEM) were not significantly different, indicating that for an equal augmentation of inotropic state, ouabain increases myocardial oxygen demands to the same extent as does norepinephrine. When the results with ouabain or norepinephrine were compared to results obtained by altering heart rate, it was found that increasing inotropic state by these pharmacologic agents is more costly in terms of myocardial energy demands than when inotropic state is enhanced by increasing heart rate.
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PMID:Comparative influence of ouabain, norepinephrine and heart rate on myocardial oxygen consumption and inotropic state in dogs. 68 7

Stria vascularis from guinea pig cochleae was incubated in vitro to determine its metabolic response to variations in substrate and ion composition of the incubation medium. The respiratory rate at 37 degrees C in a medium containing glucose and pyruvate as substrate was 17.3 +/- 1.33 (SEM, n = 51) microliter O2/mg dry weight-hour. The stria could not maintain constant respiration by relying solely upon endogenous fuel stores. With substrate supplied, the ATP level could be maintained at about 73% of that existing in vivo. Glucose appears to be an adequate substrate for stria in vitro since glutamate, pyruvate, and fumarate did not increase the respiratory rate. Succinate increased respiration markedly but did not increase the ATP level. Ouabain (10(-4) M) caused a 48% decrease in the respiratory rate. Incubation in Na+-free and K"-free medium, each resulted in irreversible decrease of respiratory rate comparable to (or greater than) that caused by ouabain. These data are in accord with the high activity of Na+-K+-ATPase in the stria and the pronounced sensitivity of the endolymphatic potential to ouabain.
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PMID:Respiratory rate and ATP content of stria vascularis of guinea pig in vitro. 71 73

Electrophysiological studies were performed in 16 patients before and 30 min after intravenous administration of ouabain (0.1 mg/kg). P-A interval (mean+/-SEM) was 40+/-2.1 ms before and 44+/- 1.5 ms after ouabain (P less than 0.001). Atrial effective and functional refractory periods (ERP and FRP) were measured in all patients during sinus rhythm and during driving at equivalent paced rates in 12 patients. The mean atrial ERP and FRP during sinus rhythm were, respectively, 244+/-10.5 and 307+/-11.0 ms before and 253+/-9.7 and 318+/-11.4 ms after infusion of ouabain (NS). Mean atrial ERP and FRP during driving were, respectively, 231+/-15.3 and 264+/-14.9 ms before and 266+/-18.6 and 296+/-19.7 ms after ouabain (P less than 0.01 and P less than 0.01). Mean sinus cycle length and sinus recovery times were, respectively, 887+/-31.2 and 1,113+/-38.7 ms before and 905+/-38.2 and 1,008+/-30.7 ms after infusion of ouabain (NS and P less than 0.005). Calculated sinoatrial conduction times before and after ouabain were 90+/-6.8 and 110+/-8.5 ms, respectively (P less than 0.005). In summary, ouabain produced depression of intraatrial conduction as manifested by increase in P-A interval and atrial effective and functional refractory periods. Ouabain significantly increased calculated sinoatrial conduction time without significant effect on spontaneous sinus cycle length.
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PMID:The electrophysiological effects of ouabain on sinus node and atrium in man. 115 73

Na+,K(+)-ATPase concentration in rat cerebral cortex was studied by vanadate-facilitated [3H]ouabain binding to intact samples and by K(+)-dependent 3-O-methylfluorescein phosphatase activity determinations in crude homogenates. Methodological errors of both methods were evaluated. [3H]Ouabain binding to cerebral cortex obtained from 12-week-old rats measured incubating samples in buffer containing [3H]ouabain, and ouabain at a final concentration of 1 x 10(-6) mol/L gave a value of 11,351 +/- 177 (n = 5) pmol/g wet weight (mean +/- SEM) without any significant variation between the lobes. Evaluation of affinity for ouabain was in agreement with a heterogeneous population of [3H]ouabain binding sites. K(+)-dependent 3-O-methylfluorescein phosphatase activity in crude cerebral homogenates of age-matched rats was 7.24 +/- 0.14 (n = 5) mumol/min/g wet weight, corresponding to a Na+,K(+)-ATPase concentration of 12,209 +/- 236 pmol/g wet weight. It was concluded that the present methods were suitable for quantitative studies of cerebral cortex Na+,K(+)-ATPase. The concentration of rat cerebral cortex Na+,K(+)-ATPase showed approximately 10-fold increase within the first 4 weeks of life to reach a plateau of approximately 11,000-12,000 pmol/g wet weight, indicating a larger synthesis of Na+,K+ pumps than tissue mass in rat cerebral cortex during the first 4 weeks of development. K+ depletion induced by K(+)-deficient fodder for 2 weeks resulted in a slight tendency toward a reduction in K+ content (6%, p > 0.5) and Na+,K(+)-ATPase concentration (3%, p > 0.4) in cerebral cortex, whereas soleus muscle K+ content and Na+,K(+)-ATPase concentration were decreased by 30 (p < 0.02) and 32% (p < 0.001), respectively. Hence, during K+ depletion, cerebral cortex can maintain almost normal K+ homeostasis, whereas K+ as well as Na+,K+ pumps are lost from skeletal muscles.
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PMID:Quantification of rat cerebral cortex Na+,K(+)-ATPase: effect of age and potassium depletion. 133 24

We tested the hypothesis that the decrease in the thyroid state, with age, contributes to the age-related increase in myocardial responsiveness to cardiac glycosides. Thyroid hormone levels (reflecting the thyroid state): total T4 (microgram/dl) and total T3 (ng/dl) in the 3 groups of guinea pigs were (mean +/- SEM): adults (3 months old): less than 1.0 and 22.6 +/- 1.1; euthyroid newborns (0-5 days old): 3.9 +/- 0.4 and 56.5 +/- 11.9; hypothyroid newborns, (0-5 days old): 1.5 +/- 0.3 and 26.5 +/- 9.8. In euthyroid newborns, T4 and T3 levels were significantly higher than in adults (p less than 0.01 for T4 and p less than 0.05 for T3) and in hypothyroid newborns (p less than 0.05). Isometric twitch was recorded from right ventricular papillary muscles by means of a force transducer. Ouabain 10(-6) M increased isometric twitch tension in adults (tension = 0.66 +/- 0.18 g/mm2) by 123.6 +/- 18.2%, in euthyroid newborns (tension = 0.19 +/- 0.04 g/mm2) by 83.6 +/- 14.5%, and in hypothyroid newborns (tension = 0.12 +/- 0.01 g/mm2) by 170.9 +/- 33.8% (p less than 0.01). Ouabain dose-response curve in the range of 10(-7) M-0.5 x 10(-5) M was significantly different (compared by two-way ANOVA) between euthyroid newborns and hypothyroid newborns (p less than 0.01), and between euthyroid newborns and adults (p less than 0.01). Toxic effects of ouabain reflected by the generation of aftercontractions were also age related and were augmented by hypothyroidism in newborns.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of thyroid state in age-dependent cardiac effects of ouabain in guinea pigs. 181 26

The interaction of the cardiotonic agent DPI 201-106 (4-[3-(4-diphenylmethyl-1-piperazinyl(-2-hydroxypropoxy]-1H-indole -2- carbonitrile) with cardiac glycosides was investigated. In rabbit papillary muscles, all effects were normalized by using potentiating paired stimulation (PPS) as the 100% reference standard. Ouabain 1 microM alone increased the force of contraction (FC) by 66% +/- 6% (SEM) of PPS; 0.1 microM was ineffective. In the presence of 0.1 microM S-(-)-DPI 201-106, the active enantiomer of DPI 201-106, ouabain 0.1 and 1 microM increased FC by 41% +/- 11% and 119% +/- 19% of PPS, respectively. In anesthetized dogs, left ventricular dP/dtmax was increased by racemic DPI 201-106 0.2 mg/kg i.v. (+1987 +/- 660 mm Hg/s) and by ouabain 35 micrograms/kg i.v. (+560 +/- 40 mm Hg/s). The combined effect of DPI 201-106 and ouabain in similar doses was +2827 +/- 942 mm Hg/s. In digoxin-pretreated anesthetized cats, racemic DPI 201-106 was infused up to an accumulated dose of 12.22 mg/kg i.v. No signs of cardiotoxicity were observed in combination. In conclusion, the concomitant administration of DPI 201-106 and cardiac glycosides leads to enhanced positive inotropic effects in vitro and in vivo. The cardiotoxicity of glycosides was not increased by DPI 201-106.
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PMID:Interaction of DPI 201-106 with cardiac glycosides. 246 68

The effect on the tegument of adult Fasciola hepatica of incubation in the sodium ionophore monensin, the Na+/K+-ATPase inhibitor ouabain and ouabain pretreatment followed by monensin has been determined in vitro by scanning and transmission electron microscopy (SEM, TEM). With monensin incubation alone (1 x 10(-6) M), a flattening of the tegument with some loss of spines on the ventral surface is evident from 0.5 h onwards. Internally, the subtegumental musculature becomes grossly swollen, although there is no swelling of the infoldings of the basal plasma membrane of the tegument, even after 24 h incubation. Ouabain incubation (1 x 10(-3) M) induces folding of the apical surface of the tegument from 0.5 h onwards, and this is accompanied by the formation of blebs and microvilli. Brief (0.5 h) exposure to ouabain (1 x 10(-3) M) followed by monensin treatment (1 x 10(-4) M, 3 h) leads to gross "vacuolation" of the tegument, but this is not due to swelling of the basal infoldings. The other main feature of ouabain-pretreated flukes is the projection of basal lamina-like material into the tegumental syncytium. Monensin treatment alone (1 x 10(-6) M) results in the Golgi complexes of the tegumental cells becoming very diffuse from 1.5 h onwards, and relatively few secretory bodies are present in the cytoplasm. After 0.5 h incubation in ouabain (1 x 10(-3) M), the Golgi complexes of the tegumental cells are indistinct, although numerous secretory bodies are still present. The classical monensin-induced swelling of the Golgi cisternae is observed in the tegumental cells only when monensin treatment (1 x 10(-4) M, 3 h) was preceded by brief (0.5 h) exposure to ouabain (1 x 10(-3) M). The results are discussed in relation to the postulated osmoregulatory role of the tegument and the role of sodium pumps in membrane function in the fluke.
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PMID:Fasciola hepatica: the effect of the sodium ionophore monensin on the adult tegument. 254 Apr 90

The relationship between erythrocyte Na,K-ATPase activity (ouabain-inhibited 86Rb uptake) and metabolic efficiency (defined as the resting metabolic rate adjusted for body composition) was examined in 31 healthy young subjects (16 men and 15 women, 19-33 yr old). Mean (+/- SEM) Na,K-ATPase activity (expressed as nanomoles of Rb taken up per h/billion erythrocytes) was similar in the men (86 +/- 3) and women (94 +/- 7). After adjusting metabolic rate for body cell mass (total body potassium), men and women had similar metabolic rates, and subjects with the highest percent body fat tended to have the highest metabolic rates. Ouabain-sensitive erythrocyte Rb uptake was related to less than 2% of the variability in resting metabolic rate after adjusting metabolic rate for differences in body composition. Erythrocyte Na,K-ATPase activity does not appear to be a useful marker of metabolic efficiency in man.
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PMID:No correlation between erythrocyte Na,K-ATPase activity and resting metabolic rate in humans. 255 May 12

Bartter's syndrome is characterized by chronic hypokalaemia, activation of the renin-angiotensin system and normal blood pressure. To investigate whether a generalized disturbance of sodium-potassium pump function might be of pathogenetic importance, lymphocytic sodium-potassium homeostasis was examined in 5 patients suffering from Bartter's syndrome. Two of the patients were treated with potassium chloride supplementation, the others were without medical treatment when studied. All were severely hypokalemic (serum potassium 2.8 +/- 0.24 mmol/l, mean +/- SEM). Lymphocyte sodium and potassium concentration (14.4 +/- 0.37 and 94.4 +/- 7.7 mmol/l, respectively), ouabain sensitive 22Na-efflux rate constant (2.68 +/- 0.25 h), and absolute ouabain sensitive efflux rate (38.16 +/- 4.2 mmol l-1 h) did not differ from matched controls. Ouabain binding capacity was 126 900 +/- 23 500 sites/cell in patients vs 50 400 +/- 17 900 in controls (p less than 0.05). In conclusion, patients with Bartter's syndrome may have an intrinsic abnormal pump function, characterized by an increased pump density and a low cation turn-over rate per pump unit.
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PMID:Lymphocytic sodium and potassium pump function in Bartter's syndrome. 274 41

We studied the effect of hydrochlorothiazide, 50 mg daily, on Na,K-adenosine triphosphatase (ATPase) activity in the red cells of 10 black men with hypertension. We also examined net sodium and potassium movement in sodium-loaded, potassium-depleted, red cells. Treatment with hydrochlorothiazide resulted in a significant increase in mean ouabain-sensitive ATPase activity (+/- SEM) from 118.4 +/- 14.6 to 158.1 +/- 15.3 nmol phosphate released per milligram of protein (P = 0.0004). Ouabain-resistant ATPase did not change. Net sodium extrusion rose significantly, from 1.62 +/- 0.27 to 2.32 +/- 0.33 mmol/L/hr (P = 0.0275). We postulate that the enhanced activity of the Na,K pump results from the volume contraction induced by the diuretic. This interpretation is consistent with the concept that the Na,K pump is inhibited in volume expansion and volume-expanded hypertension. The finding of enhanced pump activity in subjects given treatment with hydrochlorothiazide suggests a possible mechanism of the antihypertensive action of diuretic therapy.
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PMID:Effect of treatment with hydrochlorothiazide on the red cell Na,K-adenosine triphosphatase in men with hypertension. 282 24


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