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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We studied the effects of coronary occlusion and of subsequent ouabain administration on regional myocardial function, flow, and electrograms in 14 conscious dogs. Coronary occlusion resulted in a graded loss of regional function as reflected by measurements of segment length (SL), velocity of SL shortening and myocardial "work" from the normal to severely ischemic zones, along with graded flow (radioactive microsphere technique) reductions and graded elevation of the regional S-T segment. Ouabain, 20 microgram/kg, improved function in the normal zone, in which stroke shortening rose by 0.23 +/- 0.07 mm (mean +/- SE) and "work" rose by 30.2 +/- 9.5 mm Hg-mm. In moderately ischemic segments, stroke shortening rose by 0.60 +/- 0.05 mm and "work" rose by 58.1 +/- 6.1 mm Hg-mm. In the majority of severely ischemic segments, stroke shortening and "work" also increased; the average effect in all severely ischemic segments was an increase in stroke shortening of 0.35 +/- 0.10 mm and in "work" of 31.5 +/- 9.9 mm Hg-mm. In addition, ouabain reduced S-T elevation by 0.90 +/- 0.20 mV in moderately ischemic zones and by 3.14 +/- 0.35 mV in severely ischemic zones, and increased flow by 28 +/- 6% and 46 +/- 9% in moderately and severely ischemic zones, respectively. All these changes were significant, P less than 0.01. Thus, ouabain caused an improvement in perfusion of ischemic tissue, which was associated with significant enhancement of stroke shortening and "work." Most strikingly, ouabain returned normal systolic shortening to 10 severely ischemic segments which previously were akinetic.
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PMID:Effects of a cardiac glycoside on regional function, blood flow, and electrograms in conscious dogs with myocardial ischemia. 67 24

CK-3197 was developed as a selective positive inotropic agent for the treatment of congestive heart failure. We compared the hemodynamic and myocardial energetic effects of CK-3197 to ouabain in the pentobarbital-anesthetized dog. Fifteen minutes after intravenous (i.v.) administration of CK-3197 (0.1, 0.3, and 1.0 mg/kg) to five dogs, mean left ventricular (LV) dP/dt increased by 24, 68, and 109% and mean arterial pressure (MAP) decreased by 4, 9, and 18%, respectively, from basal values. CK-3197 was 11 times more potent as a positive inotropic agent than as a vasodilator. Heart rate (HR) increased by 5, 14, and 24% after these doses of CK-3197, whereas LV end diastolic pressure (LVEDP) decreased by 4 mm Hg after the highest dose of compound. LV oxygen consumption (MVO2) and stroke MVO2 increased by 9, 25, and 102% and 1, 8, and 58%, respectively, at the peak of the increases in LV dP/dt. Ouabain (0.02 and 0.03 mg/kg, i.v.) increased MAP (12 and 22%), HR (2 and 20%), and LV dP/dt (19 and 36%), with a 14 and 16% increase in LV MVO2 and a 12 and -6% change in stroke MVO2. Thus, CK-3197 is a selective, positive inotropic agent with preload reducing activity in the dog. CK-3197, similar to ouabain, produced energy-efficient positive inotropic responses with either no increase in MVO2 or increases in myocardial oxygen consumption that were less than the expected 1:1 ratio with LV dP/dt. Therefore, CK-3197 may have significant utility in the clinical treatment of congestive heart failure.
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PMID:Hemodynamic and myocardial energetic effects of CK-3197, a selective positive inotropic agent. 170 48

Subarachnoid hemorrhage was produced experimentally in cats by intracisternal injection of non-heparinized autologous arterial blood obtained by cardiac puncture under ketamine and xylazine anesthesia. Cats were sacrificed at varying time intervals between 30 min and 7 days post ictus. Measurements of resting membrane potential were recorded from smooth muscle cells of the basilar artery. These measurements were obtained by impalement from the adventitial surface of isolated but otherwise intact segments of the artery using glass microelectrodes with tip sizes less than 0.1 micron. The resting membrane potential recorded in vitro from animals previously subjected to subarachnoid hemorrhage in vivo was consistently and significantly depolarized when compared to normal controls. This depolarization was present as early as 30 min post ictus. Addition of the cardiac glycoside, ouabain, in a concentration of 10(-5)M depolarized cells from both control and experimental animals. There is a significant electrogenic pump potential contribution to the resting membrane potential of vascular smooth muscle cells. Ouabain is a potent blocker of Na+, K+-ATPase, the enzyme responsible for maintaining the cation electrochemical gradients. The depolarization recorded in these cells following subarachnoid hemorrhage is not, therefore, due to impairment of the electrogenic pump. The significance and implications of these findings are discussed.
Stroke
PMID:Altered membrane properties of cerebral vascular smooth muscle following subarachnoid hemorrhage: an electrophysiological study. I. Changes in resting membrane potential (Em) and effect on the electrogenic pump potential contribution to Em. 241 49

Ouabain and vanadate are known as potent inhibitors of Na, K-ATPase in various tissues including smooth muscles. Both agents showed contractile action on various smooth muscles in a similar fashion: stronger contractile action on the aortae of rats (WKY and stroke prone spontaneously hypertensive rats, SHRSP) and guinea-pigs, and weaker contractile actions on basilar and mesenteric arteries of the same animals. Time to peak tension, however, was far longer in ouabain-induced contraction. Phentolamine depressed ouabain-induced contractions, while vanadate-induced contractions were not affected. Elevation of K+ concentration to 20 or 30 mM potentiated vanadate-induced contraction markely, while it potentiated ouabain-induced contraction only slightly. DIDS blocked vanadate-induced contraction but showed no effect on ouabain-induced contraction. Removal of Ca abolished ouabain-induced contractions, while vanadate-induced contractions of reduced height could be observed in the absence of Ca. Verapamil depressed both ouabain- and vanadate-induced contractions of WKY and SHRSP aorte aut exhibited no effect on the guinea-pig aorta. Thus, although similarities of the action of ouabain and sodium vanadate were observed, the modes of the actions were revealed to be different in the two agents. Inhibition of Na, K-ATPase might be involved in the case of ouabain-induced contractions, and inhibition of Ca-ATPase of membranous systems might be involved in vanadate-induced contraction.
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PMID:Comparison of contractile effects of sodium vanadate and ouabain in vascular smooth muscles of guinea-pigs and rats. 303 52

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

This study examines the relation between Na+-K+ transport and metabolism in the canine brain. Cerebral oxygen and glucose consumption was measured by the sagittal sinus outflow technique. Synaptic transmission and related metabolism was blocked by pentobarbital 40 mg/kg (EEG flat). Lidocaine blocked an additional 15-20%, presumable by restricting Na+-K+ leak fluxes and reducing the demand for Na+-K+ transport. Ouabain blocked an additional 20-25% of metabolism. Ouabain also inhibited the Na+-K+ sensitive ATPase associated transport and caused a net efflux of K+ from the cellular compartment as evidenced by an increasing extracellular K+ concentration in the cortex. Accordingly, a total of 40% of metabolism in te EEG-arrested barbiturate inhibited brain could be related to Na+-K+ leak fluxes and associated transport. The remaining 60% are related to processes unidentified by this study. It is concluded that cerebral metabolism may be reduced below the hitherto described barbiturate minimum.
Stroke
PMID:Oxygen and glucose consumption related to Na+-K+ transport in canine brain. 730 61

Differing opinions about the use of digitalis in patients with cor pulmonale have led the authors to study haemodynamic effect of strophantin, a cardiotonic glycoside used as therapy of choice of decompensated cor pulmonale. Five patients with severe airways obstruction recovering from heart failure were studied. Ouabain at a dose of 0.01 mg/kg was infused into the pulmonary artery. Pulmonary artery pressure and flow were measured before, at the end of the infusion, 15 and 30 min after it. There was no change in the heart rate or mean pulmonary artery pressure and a slight increase in the pulmonary wedge pressure was observed after ouabain. The most important change concerned the pulmonary blood flow. The cardiac index rose from the initial 2.48 +/- 0.44 l/min/m2 to 3.67 +/- 1.3 l/min/m2 15 min after ouabain. The increase in cardiac output was entirely due to the increase in the stroke volume. Pulmonary vascular resistance fell from 502 +/- 208 dyn. s. cm-5 to 315 +/- 216 dyn. s. cm-5 15 min after ouabain. The findings support clinical preference for strophantin in patients with decompensated cor pulmonale.
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PMID:Effects of ouabain on pulmonary haemodynamics in patients with hypoxic pulmonary hypertension. 744 98

The response of the rat cardiovascular system to the cardiac glycoside ouabain was studied in an original model of heart failure developed on day 21 of coronary embolization with 15 microns radioactive microspheres introduced into the left ventricular cavity during ascending aortic occlusion. To examine systemic and regional hemodynamic parameters, the tracer technique with microspheres. Ouabain infused to rats with heart failure caused an increase in the index of left ventricular contractility, cardiac output, stroke volume, myocardial contractility, blood flow in most viscera and a decrease in end-diastolic pressure. The findings suggest that 21 days after coronary embolization the rats with heart failure proved more sensitive to the glycoside than did those sham-operated and thus, the presented model adequately reflects the status of the cardiovascular system when heart failure is evolving.
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PMID:[The effect of ouabain on the cardiovascular system of rats with chronic heart failure]. 832 69

Guan-fu base A (GFA) is a terpenoid alkaloid isolated from the tuber of Aconitum coreanum in our institute. GFA (20-30 mg.L-1) reduced the ventricular tachycardia (VT) and ventricular fibrillation (VF) rate induced by K(+)-free and high Ca2+ solution in Langendorf heart of rats. Pretreatment of conscious rats with GFA 2.5-10 mg.kg-1 iv, increased the amount of beiwutine necessary to produce arrhythmias. Ouabain-induced VT in conscious dogs was reverted to sinus rhythm in 1-2 min by iv GFA 9-10 mg.kg-1. GFA 10-20 mg.kg-1 iv was also found to be effective in protecting anesthetized dogs from atrial fibrillation induced by topical application of ACh. GFA 10 mg.kg-1 iv obviously decreased heart rate and prolonged the P-R interval, but slightly affected the myocardial contractility in anesthetized dogs. GFA showed no obvious effect on stroke volume and cardiac output in conscious dogs. In conclusion, GFA showed therapeutic and prophylactic effect on different models of experimental arrhythmias without causing marked effect on myocardial contractility.
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PMID:[Effects of guan-fu base a on experimental cardiac arrhythmias and myocardial contractility]. 857 77

1. Incubation of bovine adrenal chromaffin cells with veratridine (10-100 microM) during 24 h, caused a concentration-dependent release of the cytosolic lactate dehydrogenase (LDH) into the bathing medium, an indicator of cell death. Lubeluzole or its R(-) enantiomer, R91154, did not enhance LDH release. Both lubeluzole and R91154 (0.3-10 microM) decreased the veratridine-induced LDH release. 2. Penfluridol did not increase LDH release at concentrations 0.003-1 microM; 3-10 microM increased LDH release to 50-60%, after 24 h exposure. Penfluridol (0.03-0.3 microM) did not protect against the cytotoxic effects of veratridine; at 1 microM, 15% protection was produced. Higher concentrations (3-10 microM) enhanced the cytotoxic effects of veratridine. 3. Ba2+ ions caused a concentration-dependent increase of LDH release. This cytotoxic effect was partially prevented by 3 microM lubeluzole and fully counteracted by 1 microM penfluridol. R91154 was less potent than lubeluzole and only protected against the lesion induced by 0.5 mM Ba2+. 4. Ouabain (10 microM during 24 h) increased LDH release to about 30%. Both lubeluzole (0.3-10 microM) and the lower concentrations of penfluridol (0.003-0.3 microM) prevented the ouabain cytotoxic effects. At higher concentrations (3 microM), penfluridol increased drastically the ouabain cytotoxic effects. 5. 6-Hydroxydopamine (6-OHDA) caused significant cytotoxic effects at 30 and 100 microM. Lubeluzole (3-10 microM) or penfluridol (0.03-0.3 microM) had no cytoprotective effects against 6-OHDA. 6. Lubeluzole (3 microM), R91154 (3 microM) and penfluridol (1 microM) blocked the current through Na+ channels in voltage-clamped chromaffin cells (I(Na)) by around 20-30%. Ca2+ current through Ca2+ channels (I(Ca)) was inhibited 57% by lubeluzole and R91154 and 50% by penfluridol. The effects of penfluridol were not washed out, but those of lubeluzole and R91154 were readily reversible. 7. Lubeluzole (3 microM) induced reversible blockade of the oscillations of the cytosolic Ca2+, [Ca2+]i, in fura-2-loaded cells exposed to 30 or 100 microM veratridine. Penfluridol (1 microM) inhibited those oscillations in an irreversible manner. 8. The results suggest that lubeluzole and its R-isomer caused cytoprotection against veratridine cell damage, by blocking the veratridine stimulated Na+ and Ca2+ entry, as well as the [Ca2+]i oscillations. The Ba2+ and ouabain cytotoxic effects were prevented more efficiently by penfluridol, likely by blocking the plasmalemmal Na+/Ca2+ exchanger. It remains dubious whether these findings are relevant to the reported neuroprotective action of lubeluzole in stroke; the doubt rests in the stereoselective protecting effects of lubeluzole in in vivo stroke models, as opposed to its lack of stereoselectivity in the in vitro model reported here.
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PMID:Effects of the neuroprotectant lubeluzole on the cytotoxic actions of veratridine, barium, ouabain and 6-hydroxydopamine in chromaffin cells. 972 Jul 90


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