Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ouabain produces a greater degree of prolongation of the P-R interval than digitoxin in rats when dosages which produce similar inotropic responses are used. When digitoxin is administered after pretreatment with propranolol, it produces prolongation of the P-R interval comparable to that produced by ouabain. Indications in the literature that these findings may apply to human beings suggest that in some situations atrial fibrillation may be better controlled with a hydrophilic digitalis preparation (e.g. ouabain), whereas cardiac failure with a tendency to atrioventricular block may be better controlled with a lipophilic preparation (e.g. digitoxin).
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PMID:A specific cardiac glycoside for cardiac failure and another for atrial fibrillation? 55 Apr 38

The effect of 0.25 mg ouabain on cerebral blood flow (CBF) was investigated in patients with and without cerebrovascular disease using the xenon clearance method. The 36 patients included in this study did not show any signs of heart failure. Ouabain increased the CBF and this effect was demonstrable 15, as well as 90 min. after administration. This effect was proven statistically using the t-test for a comparison of the values with spontaneous changes in a control group without medication. The perfusion of pathologically-supplied brain regions was altered in the same way as the hemispheric flow; changes in the distribution of blood in the way of a steal effect were not observed. The haemodynamic parameters do not indicate a primary cardiac effect. Hence, an influence of ouabain on cerebral vessels might be responsible. The present results support reported clinical experience with ouabain for the treatment of patients with cerebrosvascular disease.
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PMID:[Effect of Ouabain on cerebral blood flow (author's transl)]. 97 77

Blunted cardiac responses to sympathetic and vagal activation are key features of heart failure. Since the modulation of drug effects by a selective autonomic dysfunction is little known, we developed an acute rabbit model imitating these defects. Anesthetized rabbits were subject to cervical vagotomy and propranolol (1 mg/kg i.v.) pretreatment, thus eliminating vagally and sympathetically mediated cardiac responses, while maintaining the responsiveness of the peripheral circulation to these reflexes ("V-B" animals). Responses to drugs were altered in V-B compared with normal animals: Ouabain (5-50 micrograms/kg) increased myocardial contractile force more and milrinone (30-300 micrograms/kg) less, yet it increased the heart rate more; the reflex tachycardia to nitroprusside (1-10 micrograms/kg/min) was blunted and spirapril (0.1 and 1 mg/kg, all i.v.) decreased the central venous pressure only in V-B animals. Several drug effects were thus strongly modulated by autonomic dysfunction and responses of V-B animals were closer to those of heart failure patients than the responses of the normal animals, especially for milrinone.
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PMID:Autonomic nervous system dysfunction alters drug effects: implications for testing drugs for the treatment of heart failure. 138 21

In isolated papillary muscle strips from nonfailing donor hearts (NF) and from the hearts of patients with dilated cardiomyopathy with severe heart failure (NYHA IV), the force-frequency relationship was studied. Experiments were performed under basal conditions and in the presence of 0.01 microM or 0.1 microM isoprenaline and 0.02 microM ouabain. In NF, there was a positive inotropic effect following an increase of the stimulating frequency, whereas in NYHA IV, the force gradually declined under these conditions. Low concentrations (0.01 microM) of isoprenaline prevented the negative inotropic effect in NYHA IV, whereas at 0.1 microM the mechanical function deteriorated in NF and NYHA IV. Ouabain had no effect on the force-frequency relationship compared to basal conditions. It is concluded that a reduction of high frequencies does improve the contractility in the failing myocardium. It is not unreasonable to speculate that this mechanism might be involved in the beneficial effects of drugs which reduce the heart rate, such as beta-adrenoceptor antagonists and cardiac glycosides, in the condition of congestive heart failure in which the sympathetic tone is high.
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PMID:Force-frequency relationship and inotropic stimulation in the nonfailing and failing human myocardium: implications for the medical treatment of heart failure. 160 Mar 53

We investigated the "receptor-effector-coupling" in the beta-adrenoceptor- and the Na+, K(+)-ATPase-mediated systems in nonfailing hearts and terminally failing human myocardium from patients with cardiomyopathy. The density of beta-adrenoceptors in the failing human myocardium was significantly (p less than 0.01) lower as compared with nonfailing hearts, whereas the receptor density and affinity measured by [3H]ouabain binding (cardiac glycoside receptor) was not different in either group. The maximal inotropic response to isoprenaline was significantly reduced in papillary muscle strips from failing human hearts (2.1 +/- 0.5 mN) as compared with control hearts (8.0 +/- 1.0 mN; p less than 0.05). Ouabain remained effective in both groups (6.8 +/- 1.0 vs. 5.5 +/- 0.6 mN; NS). The positive inotropic response due to extracellular Ca2+ elevation (1.8-15 mM) was studied for comparison. Maximal Ca2+ effects were reduced by 30% in failing human myocardium (7.2 +/- 0.5 mN vs. 5.1 +/- 0.8 mN, p less than 0.05). Ouabain had effectiveness (95%) similar to that of Ca2+ in nonfailing and failing human cardiac muscle. It is concluded that treatment with cardiac glycosides may still be effective in end-stage heart failure with "downregulated" beta-adrenoceptors, as judged from these in vitro studies.
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PMID:Effectiveness of cardiac glycosides in human myocardium with and without "downregulated" beta-adrenoceptors. 169 27

New method for measuring plasma and urinary Na-K-ATPase inhibitor (ATPI) was developed. Plasma and urine were extracted with reversed phase cartridge column and sample was reconstituted by assay buffer. Na-K-ATPase inhibitory activity of sample was monitored by continuously recording the absorbance of NADH at 340 nm, which coupled to the dephosphorylation of ATP. Ouabain was used for standards of Na-K-ATPase inhibition and this standard showed good linearity ranged 5-100 nmol/ml. Using this new method, P-ATPI and U-ATPI were quantitatively evaluated and paradoxical Na-K-ATPase stimulating phenomenon which observed in conventional method (Hamlyn et al) was diminished. Adopting of this new method for measuring plasma(P-) and urinary(U-)ATPI, and radioimmunoassay for P- and U-digitalis-like substance(DLS)--using crossreactivity to anti digoxin antibody--, these substances were estimated in patients with essential hypertension (EHT), chronic heart failure(CHF), primary and idiopathic hyperaldosteronism(HA), hyperthyroidism(BA) and chronic renal failure(CRF). In EHT, U-DLS, P-DLS, U-ATPI, P-ATPI were significantly higher than those of control(C). In CHF and BA, U-DLS and -ATPI were also significantly higher than those of C. In HA, U-ATPI, DLS distributed in wide range, and a few patients showed high levels of U-DLS and -ATPI. In CRF, P-DLS and -ATPI levels were significantly higher than those of C in prehemodialytic state but P-ATPI was significantly decreased after hemodialysis. From these results it is suggested that 1) DLS and ATPI might contribute to the etiology of hypertension. 2) Volume expansion stimulates the secretion of DLS and ATPI. 3) Stimulatory effect of volume expansion and inhibitory effect of mineralocorticoid may be responsible for wide distribution of these factors in HA. 4) DLS and ATPI are not the same substances.
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PMID:[Endogenous digitalis-like substance and Na-K-ATPase inhibitor in cardiovascular and renal disease]. 283 14

In previous experiments PY 108-068 (PY) has been found to have more potent calcium antagonistic effects on vascular smooth muscle than on myocardial tissue. We now investigated the effects of PY and verapamil (V) on the increases in myocardial contractile force (measured with a strain gauge) and regional vasoconstriction (measured with tracer microspheres) effected by an infusion of 40 micrograms/kg ouabain into anaesthetized cats. Ouabain significantly increased contractile force of the left ventricle and caused vasoconstriction in the heart, stomach, small intestine, pancreas, spleen and skin, but not in the kidneys, brain, adrenals and liver. PY (30 micrograms/kg i.v.) and V (0.3 mg/kg i.v.) antagonized the vasoconstrictor effects of the glycoside in all organs except the skin, i.e. also in organs, where the calcium antagonists normally do not cause vasodilatation. However, PY did not affect the increase in contractile force, whereas V attenuated both the cardiac and peripheral vascular effects of ouabain. The results demonstrate the preferential action of PY on peripheral blood vessels as opposed to left ventricular myocardial tissue. Heart rate was decreased by both PY and V but the PQ-interval was lengthened only by V suggesting that PY in contrast to V preferentially acts on the sinus node rather than A-V conduction. A combination of PY with a glycoside might be beneficial in the treatment of cardiac failure, since this calcium antagonist apparently does not antagonize the positive inotropic action of ouabain on the heart while reducing afterload and reversing the undesirable vasoconstriction induced by cardiac glycosides.
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PMID:PY 108-068, a dihydropyridine derivative, and verapamil interact differently with the ouabain effects on the heart and the peripheral circulation. 398 26

Amrinone, a positive inotropic-vasodilator agent, was administered to anaesthetised dogs in an attempt to reverse heart failure induced by drugs possessing negative inotropic properties. Propranolol, a beta-adrenergic blocker; verapamil, a calcium slow-channel blocker procainamide, a type 1 antiarrhythmic agent; or sodium pentobarbital, a barbituate; administered as a bolus injection and/or infusion, produced a sustained depression in canine cardiac function. Cardiac depression was characterised by a greater than 40% reduction in cardiac contractile force (CF) and maximum left ventricular pressure development (LV dp/dtmax), a 30 to 50% reduction in cardiac output (CO) and concomitant increases in mean central venous or mean right atrial blood pressures (CVP, RAP, respectively). Amrinone, when administered intravenously as a bolus injection (1 or 3 mg X kg-1) plus an infusion (0.03 or 0.1 mg X kg-1 X min-1) reversed the depression in cardiac function by increasing CF, CO and LV dp/dtmax and decreasing preload CVP or RAP in all four drug-induced failure models. Due to the vasodilator properties of amrinone, afterload, total peripheral resistance (TPR), was reduced in verapamil and procainamide failures as well as in propranolol failure, the only model where TPR increases. In another model of heart failure, in which ouabain-induced arrhythmias preceded procainamide toxicity, amrinone was also an effective cardiotonic agent. Ouabain's inotropic effect was studied in propranolol-induced heart failure. Although an increase in LV dp/dtmax and a decrease in CVP were noted, ouabain (40 micrograms X kg-1 iv) increased TPR and had little effect on the depression in CF and CO. Drug-induced models of heart failure were useful pharmacological tools for evaluating the cardiotonic agent's ability to overcome severe cardiac depression. In propranolol-, verapamil-, procainamide-, and pentobarbital-induced cardiac toxicity, amrinone could be of therapeutic value.
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PMID:The beneficial effect of amrinone on acute drug-induced heart failure in the anaesthetised dog. 404 15

Experiments were performed on 5 resting conscious dogs supplied with an electromagnetic flow probe on the ascending aorta and a chronic aortic catheter for pressure recording. The animals were used repeatedly in four different types of experiment involving i.v. administration of 1. saline (controls), 2. prenalterol 45 nmol/kg (approximately 10 micrograms/kg) followed by an additional dose of 135 nmol/kg 20 min later, 3. ouabain 50 nmol/kg (approximately 30 micrograms/kg) and 4. a combination of protocols 2. and 3. Ouabain and the low dose of prenalterol exerted clear-cut positive inotropic effects as reflected in increased stroke volume and max dF/dt without significant changes in heart rate or arterial pressure. The PQ interval increased with ouabain but decreased with prenalterol. The higher dose of prenalterol caused a further rise in max dF/dt, a further shortening of the PQ time, increased heart rate and reduction in systemic vascular resistance. Higher doses of ouabain could not be given due to side-effects (vomiting). The combined treatment with ouabain and prenalterol showed their inotropic responses to be additive. Arrhythmias did not occur in any of the animals at the applied dose levels of the drugs. The experiments show that prenalterol through its beta 1-adrenoceptor stimulating action exerts a positive inotropic effect which surpasses that of emetic doses of ouabain. The inotropic response at moderate doses occurs without a change in heart rate. This fact and the apparent lack of influence of prenalterol on vascular alpha- and beta 2-adrenoceptors make the substance potentially useful clinically as an inotropic agent in cardiac failure, particularly in view of its relatively long duration of action.
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PMID:The haemodynamic effects of intravenous prenalterol and ouabain in conscious dogs. 612 99

Due to fundamental considerations and especially after Braunwald's et al. (1962 (4)) examinations of 5 patients with severe hypertrophic obstructive cardiomyopathy (HOCM) with 0.5-0.75 mg of Ouabain, cardiac glycosides in cases of this disease are to be regarded as contraindicated. Own examinations (right and left-heart catheterizations, monoplane cineangiography of the left ventricle, determination of the cardiac output, and the ejection fraction (EF) were performed in 10 patients with HOCM of different stages. Applying the usual dosage of 0.25-0.375 mg of strophanthin, different hemodynamic effects were observed in discrete forms. In cases with a higher severity, the observations of Braunwald et al. could actually be confirmed. The left ventricular systolic pressure gradients were increased, but cardiac output, left ventricular enddiastolic pressure, pulmonary pressure and resistance, and also arterial pressure and peripheral resistance behaved differently. EF increased slightly. The right infundibular gradients were decreased with one exception, or resp., they were unchanged. Obviously, HOCM reacts especially unfavourably with so-called left-ventricular cavity obliteration. The main importance might belong to the behaviour of the free lumen of the left ventricle. In regard of the principally reserved attitude towards the cardiac glycoside therapy in HOCM, no change has occurred. Only in patients with atrial fibrillation and a rapid heart rate, a therapy trial could be considered, if necessary in combination with beta-blocking agents or calcium antagonists under hemodynamic control. In cases of HOCM with serious obstruction and signs of cardiac failure and inadequate affecting by calcium antagonists, an early surgical intervention should be executed.
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PMID:[Hemodynamic examinations concerning the effects of cardiac glycosides in hypertrophic obstructive cardiomyopathy (HOCM)]. 689 Feb 76


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