Chagasic sera alter the effects of ouabain on isolated rat atria. Participation of adrenergic mechanisms (original) (raw)
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Effects of an endogenous ouabainlike compound on heart and aorta
Hypertension, 1991
An endogenous ouabainlike compound (OLC) has been purified from human plasma, and mass spectrometry has shown it to be indistinguishable from plant-derived ouabain. This human OLC was tested for its effects on evoked tension in guinea pig left atria and aortic rings. The tissues were incubated at 37 degrees C in bicarbonate-buffered physiological salt solution gassed with 95% O2-5% CO2. In atria stimulated electrically at 1 Hz, 85 and 170 nM human OLC increased peak active force to 177 +/- 15% and 313 +/- 32% of control, respectively (n = 3), with little effect on the duration of contraction. On washout of the OLC, peak systolic force returned to the control level with a half-time of 4.3 +/- 0.5 minutes. Similar results were obtained with 160 nM plant-derived ouabain: peak systolic force increased to 310 +/- 31% of control (n = 4) and returned to the control level with a half-time of 3.8 +/- 0.2 minutes during washout. In aortic rings, neither 170 nM human OLC nor 160 nM plant ouaba...
Relationship between Heart Rate and Ouabain Toxicity in the Dog Heart-Lung Preparation
Japanese Heart Journal, 1973
Cardiac arrest Cardiac arrhythmia Cardiotoxicity Heart rate Ouabain Ventricular fibrillation Ventricular tachycardia N the recent years, several investigations have been carried out in an attempt to study the relationship between the onset of positive inotropic action of digitalis glycosides and different parameters of the cardiac function.27),32),36) These observations suggest that the onset of the pharmacological action of the digitalis glycosides is dependent upon either the heart rate,8),17),21),26),33),35) or the duration of exposure to the glycoside or both.32) However, little information is available concerning the toxicity of digitalis glycosides with regard to these factors. The present series of investigations was undertaken to determine if the dose of ouabain necessary to produce cardiac arrhythmias (toxic dose) and ventricular fibrillation or cardiac arrest (lethal dose) can be influenced by different heart rates. The dog heartlung preparation was employed in this study to minimize factors which may influence the direct effect of ouabain on the myocardium .
Proceedings of the National Academy of Sciences, 1980
Isolated left atria from guinea pigs were stimulated at 3.3 Hz and bathed at 30'C in Tyrode's solution containing 6 mM KCL. After equilibration, this solution was replaced by a low-K solution or by Tyrode's solution containing ouabain or dihydroouabain. These treatments evoked an increase in the contractility of the atria. The time to peak increase was about 30 min, and the inotropic effect was sustained for at least 40 min. After 30 min, 42K was added to the bathing solution in order to estimate the activity of the Na+/K+ pump. A linear
Ouabain attenuates cardiotoxicity induced by other cardiac steroids
British Journal of Pharmacology, 2010
This is an Accepted Article that has been peer-reviewed and approved for publication in the British Journal of Pharmacology, but has yet to undergo copy-editing and proof correction. Please cite this article as an "Accepted Article"; Summary Background and purpose: All cardiac steroids have a similar structure, bind to and inhibit the ubiquitous transmembrane protein Na + , K + -ATPase and increase the force of contraction of heart muscle. However, there are diverse biological responses to different cardiac steroids both at the cellular and at the molecular level. Moreover, we have recently shown that ouabain inhibits digoxin-and bufalin-induced changes in membrane traffic. The present study was designed to test the hypothesis that ouabain also has an inhibitory effect on cardiotoxicity induced by other cardiac steroids.
Significance of the number of stimuli to initiate ouabain-induced arrhythmias in the intact heart
Circulation Research, 1991
Ouabain-induced arrhythmias are a well-known model used to study triggered activity resulting from delayed afterdepolarizations. In the intact heart, initiation of these arrhythmias is promoted by pacing, especially at fast rates. However, the relevance of the number of stimuli is unknown. In conscious dogs with formalin-induced atrioventricular block, we investigated the effect of variations in pacing mode on 1) the behavior of nonsustained triggered rhythms at progressive levels of ouabain intoxication, and 2) the induction of sustained ventricular tachycardia (VT). Twenty experiments were analyzed. Ouabain was administered as a bolus of 40 micrograms/kg followed by continuous infusion. Every 15 minutes the pacing protocol was repeated, with a maximum of 10, until completion or induction of VT. When VT could not be initiated, the experiment was repeated at least 1 week later, adding 5-10 micrograms/kg ouabain to the bolus and increasing the infusion rate correspondingly. This was ...
European Journal of Pharmacology, 1988
In intact heart muscle cells incubated in a physiological solution, i.e. under the condition in which the cardiac glycosides produce pharmacological and toxicological effects, receptors for these actions of the glycosides should be available to ouabain. In cell homogenates, [3H]ouabain binding observed in the presence of Mg 2+ and inorganic phosphate represents binding of the glycoside to Na+,K+-ATPase. Therefore, numbers of these two types of [3H]ouabain binding sites were compared using viable myocyte preparations obtained from ventricular muscle of guinea-pig heart. The number of ouabain binding sites observed in viable myocytes in the absence of Ca 2÷ and K + was not different from the number of ouabain binding sites on Na÷.K+-ATPase observed with sodium dodecylsulfate-treated homogenates prepared from isolated myocytes. These results do not support the hypothesis that there are receptors for the pharmacological or toxic actions of ouabain other than those that are associated with sarcolemmal Na+,K +-ATPase.
British Journal of Clinical Pharmacology, 2001
Aims To investigate whether the inotropic effect of ouabain in failing human myocardium varies according to the heart chamber tested (right or left ventricle) or the aetiology of the heart disease, i.e. ischaemic or idiopathic. Methods The inotropic effect of ouabain was measured, as the percentage change in baseline tension, in myocardial strips isolated from right (RV; n=21) and left ventricles (LV; n=21) of hearts explanted from patients with idiopathic (IDC; n=11) and ischaemic cardiomyopathy (CAD; n=10). Concentration-effect curves obtained with ouabain (0.05-1.6 mmol l −1) were analysed using the E max sigmoidal model, and the following parameters were calculated: E max , EC 50 , n and EC 10 (threshold concentration). The influence of ventricular chamber and heart failure aetiology on these parameters was evaluated by means of a two-way anova. Results Age and baseline haemodynamic parameters did not differ between IDC and CAD patients. Baseline strip contractility was highly variable (range: 0.48-10.0 mN), but neither ventricular chamber nor aetiology could explain such variability. A two-way anova showed that EC 10 was greater in CAD than in IDC preparations (0.097±0.013 mmol l −1 vs 0.059±0.009 mmol l −1 ; 95% C.I. for difference 0.043, 0.071) and E max was lower in RV than in LV (121±21% vs 250±38%; 95% C.I. −221, −36), while EC 50 and n were not significantly different between groups. Conclusions The inotropic effect of ouabain in human myocardium may vary according to aetiology of heart failure and the ventricle being tested. Although our results do not support the hypothesis of increased sensitivity to cardiac glycosides in CAD patients, they may explain the diminished effect observed in patients with RV failure.