Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.6.1.3 (ATPase)
65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability to induce alcoholic cardiomyopathy has been tested in a variety of animal species. Myocardial alterations consistent with subclinical heart disease have been produced in many of these studies through a direct effect of ethanol or its metabolites upon the heart or a neurohumoral mechanism. In the rat most studies have, however, failed to finding diminished contractility in the basal state. In long-term animals the acute left ventricular responses to isoproterenol and calcium as well as pacing were reduced. Long-term studies in mongrel dogs fed 36 per cent of calories as ethanol produced an early decrease in left ventricular diastolic compliance related to interstitial collagen accumulation. Diminished contractility developed by four years. In addition to the morphologic evidence of distorted sarcoplasmic reticulum, in vitro experiments suggest important acute effects. Each mole of ethanol is bound tightly to each mole of protein comprising the Ca-ATPase pump, which is inhibited. Impaired uptake and binding of calcium by the sarcoplasmic reticulum has been observed in chronic alcohol models at one to two day intervals following the last exposure to ethanol. In addition, the flux of calcium ion does not appear normal in terms of access to contractile protein, where the calcium regulated inhibition of the troponin interaction with myosin is impaired. Experimental studies in a canine model of alcoholism revealed that the ventricular fibrillation threshold was moderately reduced in the basal state after 18 months and was diminished further after acute exposure.
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PMID:Experimental models for studying the effects of ethanol on the myocardium. 331 64

Experiments on rats and rabbits using models of arrhythmias induced by vasopressin, epinephrine, strophanthin, and CaCl2 showed that antioxidants derived from 1,4-dihydropyridines, dibunol, and alpha-tocopherol possessed antiarrhythmic effects. Administration of these antioxidants decreased the occurrence of extrasystoles, disturbances of atrioventricular conductivity and ventricular fibrillation. These drugs also prevented changes in membrane phospholipid composition, inhibited activation of peroxidation, decreased phospholipase activity, prevented a decrease of Ca2+ ATPase and Ca2+ binding and uptake by sarcoplasmic reticulum, and increased sarcolemmal Na+, K+-ATPase, sarcoplasmic reticulum creatine phosphokinase.
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PMID:Antioxidants as antiarrhythmic drugs. 356 51

alpha-Adrenergic blockade with phentolamine or prazosin but not beta-adrenergic blockade reduces premature ventricular complexes and abolished ventricular fibrillation induced by coronary artery ligation or reperfusion in cats. The protective influences were independent of regional coronary flow or systemic hemodynamics. Efferent sympathetic nerve stimulation increased the idioventricular rate (IVR) prior to myocardial ischemia, a response blocked by propranolol, whereas during reperfusion the increased IVR was abolished only by alpha-blockade. Enhanced alpha-adrenergic responsiveness during reperfusion was also apparent with the alpha-agonist methoxamine. More recently we have demonstrated that alpha-adrenergic receptors, assessed by ligand binding with 3H-prazosin, increased nearly twofold in ischemic myocardium by 30 minutes (Bmax = 14 + 2 to 27 + 3 fmol/mg prot) and remain elevated during early reperfusion (12 + 1 to 18 + 1) before returning to control values by 15 minutes after reperfusion. 3H-DHA binding or Na+- -K+ adenosine triphosphatase activity was not altered at any time, indicating the specificity of the alteration. Thus enhanced alpha-adrenergic receptors and suggests the potential use of alpha-adrenergic blockade as one intervention to alleviate these malignant dysrhythmias.
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PMID:Enhanced alpha-adrenergic responsiveness in ischemic myocardium: role of alpha-adrenergic blockade. 611 77

Intractable ventricular tachyarrhythmia associated with hypomagnesemia responds well to magnesium given intravenously. Two patients with recurrent ventricular tachycardia and ventricular fibrillation associated with normal serum magnesium levels and resistant to treatment with potassium chloride, lidocaine and bretylium tosylate responded dramatically to the administration of magnesium sulfate. A third patient in whom the serum magnesium level was unknown also showed dramatic response to magnesium therapy. Magnesium depletion probably interferes with sodium-potassium adenosine triphosphatase enzyme activity and causes ionic imbalance and electrical instability of purkinje's fibers. Without obvious magnesium depletion this element in high concentration may still prolong transient inward current, prolong the effective refractory period, increase the membrane potential and control ventricular tachyarrhythmia. When ventricular fibrillation or malignant ventricular tachycardia cannot be controlled with lidocaine and other conventional drugs, we recommend infusing magnesium sulfate, 2 to 3 grams in one minute, followed by 10 grams over five hours.
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PMID:Magnesium therapy for intractable ventricular tachyarrhythmias in normomagnesemic patients. 661 8

Purified Fab fragments of ovine anti-digoxin antibodies (Wellcome Foundation) were used to treat a patient who attempted suicide by absorbing 10 mg of digitoxin (serum concentration 265 micrograms/l). The poor prognosis, as assessed clinically and from serum potassium levels (7.5 mEq/l), seemed to warrant such a treatment. The weak (6.85%) cross-reactivity elicited in vitro between the anti-digoxin antibodies and digitoxin was compensated by increasing the doses, but improvement was observed with 3.6 g, i.e. about half the effective dosage initially considered. The criteria of effectiveness were clinical, electrocardiographic (reversal of the ventricular fibrillation), biochemical (simultaneous and opposite changes in extra- and intracellular potassium levels, suggesting that ATPase inhibition by digitalis is a reversible process) and toxicological: there was an increase in digitoxin serum levels suggesting displacement of the drug from tissue sites to plasma and other extracellular compartments where the Fab fragments are distributed, and Fab-bound digitoxin appeared fairly rapidly in the urine, which suggested shunting of the normal hepatic metabolic pathway.
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PMID:[Digitoxin poisoning: reversing ventricular fibrillation with Fab fragments of anti-digoxin antibody]. 716 76

The effects of dietary supplementation with eicosapentaenoic acid (EPA) on ventricular arrhythmias during myocardial infarction were examined in a canine model. EPA was incorporated into cellular membranes after ingestion of EPA-ester (100 mg/kg body weight/day) for 8 weeks. The ratio of EPA to arachidonic acid (AA) in platelet cell membranes and myocardial microsomes was significantly increased (7% to 37% in platelet cell membranes; p < 0.01, 3% to 12% in non-infarcted cardiac microsomes; p < 0.01, and from 2% to 8% in infarcted cardiac microsomes; p < 0.01). Dietary supplementation with EPA significantly reduced the incidence and severity of arrhythmias during coronary artery occlusion. Immediately after coronary artery occlusion, all of the animals in the control group that were given a toxic dose of digitalis developed ventricular tachycardia (VT) or ventricular fibrillation (Vf), whereas none of the animals in the EPA-supplement group developed VT or Vf within 15 min after administration of digitalis. Regardless of the presence of an infarcted area, the specific activity of the Ca(2+)-pump enzyme ((Ca(2+)-Mg2+)-ATPase) within the myocardial microsomal fraction of the EPA-supplemented group was significantly higher than in that of the control group (Vmax: 140.5 +/- 19.1 vs 94.8 +/- 28.9 nmol/mg/min in non-infarcted cardiac microsomes, p < 0.01, 130.9 +/- 18.4 vs 90.2 +/- 26.4 nmol/mg/min in infarcted cardiac microsomes, p < 0.01, EPA vs control group, respectively). The specific activities of the Na(+)-pump enzyme ((Na(+)-K+)-ATPase) and NADPH-dependent cytochrome C reductase in infarcted and non-infarcted cardiac microsomes did not differ between these groups. These results indicate that EPA supplementation increases the (Ca(2+)-Mg2+)-ATPase activity within myocardial membranes that is involved in Ca2+ metabolism in myocardial cells by increasing the ratio of EPA to AA within cellular membranes. These cellular alterations are likely to reduce the severity of ventricular arrhythmias by inhibiting the rapid accumulation of intracellular Ca2+ following ischemia.
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PMID:Antiarrhythmic effects of eicosapentaenoic acid during myocardial infarction--enhanced cardiac microsomal (Ca(2+)-Mg2+)-ATPase activity. 769 37

Isolated perfused rat heart model was used to observe the protective effects of berbamine on myocardial ischemia/reperfusion injury. The hearts were remarkably injured by 40 min global ischemia followed by 20 min reperfusion. Berbamine could significantly improve heart function, prevent ventricular fibrillation, reduce CK release, preserve Na, K-ATPase activity, and reduce Na+ gain and K+ loss during ischemia and Ca2+ overload during reperfusion. With the use of low temperature ESR technique, we found that, in hearts subjected to 40 min ischemia and 15 sec reperfusion, oxygen-centered free radical signals became much more intense. In the presence of berbamine, these signals decreased. The results showed that berbamine could alleviate myocardial ischemia/reperfusion injury. This effect might be due to (1) preserved myocardial Na, K-ATPase activity and inhibition of sodium overload at the end of ischemia, which might further lead to attenuation of reperfusion-induced calcium overload, and (2) reduction of oxygen free radical generation during reperfusion.
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PMID:[Mechanism of the protective effects of berbamine on ischemia-reperfusion injury in isolated rat heart]. 820 Mar 15

The early period of reperfusion of ischaemic myocardium leads to a high incidence of severe tachyarrhythmias including ventricular fibrillation (VF), accompanied by a sudden transitional dysfunction. Oxygen free radicals (OFR) have been identified as one of the principal factors responsible for reperfusion-induced events. However, direct evidence for participation of OFR in the arrhythmogenic mechanisms upon reperfusion is still lacking. In the present study, in isolated Langendorff-perfused rat hearts subjected to 30 min global ischaemia, the onset of reperfusion induced 100% incidence of both ventricular tachycardia (VT) and VF with their gradual cessation during 5 min of reperfusion. Generation of H2O2 in the myocardium in the first minutes of reperfusion was demonstrated by means of cerium cytochemistry. There was an increased density of cerium perhydroxide precipitate distributed throughout the myocytes and endothelial cells, confirmed by X-ray microanalysis. The mechanism of the arrhythmogenic effect of OFR may involve the inhibition of the sarcolemmal Na+/K+ ATPase activity, as was revealed by subjecting the isolated sarcolemmal fraction of rat heart to the action of an oxy-radical generating system (H2O2 + FeSO4).
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PMID:High arrythmogenesis during early reperfusion of ischaemic myocardium: participation of oxygen free radicals. 866 50

We studied the effects of acidic reperfusion on 1) the incidence of ventricular fibrillation (VF) and 2) sarcolemmal Na(+)-K(+)-adenosinetriphosphatase (ATPase) activity. Isolated rat hearts (n = 12/group) were subjected to independent perfusion (15 min) of left and right coronary beds with pH 7.4 buffer followed by zero-flow ischemia (10 min) of the former bed. This was then reperfused for 5 min, with acidic (pH 6.6) buffer for the first 0 (control), 0.5,1,2, or 4 min and with pH 7.4 buffer thereafter. In the control group, 92% of hearts developed VF within 20 s of reperfusion and remained in VF. In the 0.5-, 1-, 2-, and 4-min acidic reperfusion groups, only 17, 17, 42, and 25% of hearts (P < 0.05 vs. control for all groups), respectively, exhibited VF during acidic reperfusion. However, on switching to pH 7.4, VF occurred in a further 50, 58, 0, and 0% of hearts, respectively; thus the overall incidences of VF were 67, 75, 42 (P < 0.05 vs. control), and 25% (P < 0.05 vs. control), respectively. Additional hearts (n = 8/group) were used for cytochemical determination of sarcolemmal Na(+)-K(+)-ATPase activity in both the ischemic/reperfused left ventricular (LV) and the nonischemic right ventricular (RV) free walls. Ischemia (10 min) reduced LV Na2(+)-K(+)-ATPase activity from 110 +/- 8 to 25 +/- 3% of the RV value. After 0.5, 1, 2, 3, and 4 min of acidic reperfusion, LV Na(+)-K(+)-ATPase activity was 24 +/- 3, 29 +/- 3, 37 +/- 5, 55 +/- 6, and 70 +/- 4, respectively (P < 0.05 vs. 10-min ischemia). No significant recovery of LV Na(+)-K(+)-ATPase activity occurred following up to 4 min of pH 7.4 reperfusion. In conclusion, 1) at least 2 min of acidic reperfusion is required to achieve sustained protection against VF and 2) the protective mechanism may involve enhanced recovery of Na(+)-K(+)-ATPase activity as well as inhibition of Na+ influx.
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PMID:Effects of acidic reperfusion on arrhythmias and Na(+)-K(+)-ATPase activity in regionally ischemic rat hearts. 878 Jan 91

Presently, the only therapy for ventricular fibrillation is delivery of high-voltage shocks. Despite "successful defibrillation," patients may have poor cardiac contractility, the mechanisms of which are unknown. Intracellular Ca2+ handling by the sarcoplasmic reticulum (SR) plays a major role in contractility. We tested the hypothesis that defibrillation shocks interfere with Ca2+ transport function of cardiac SR. Rats anesthetized with pentobarbital sodium had bilateral electrodes implanted subcutaneously for transthoracic shocks. A series of 10 shocks, 10 s apart, at 0-250 V was delivered from a trapezoidal defibrilator. The hearts were rapidly removed, SR-enriched membrane vesicles were isolated, and ATP-dependent Ca2+ uptake and Ca(2+)-stimulated ATP hydrolysis were determined. There was a marked, shock-related decline in Ca2+ uptake, whereas adenosinetriphosphatase activity remained unaltered. The polypeptide compositions were similar in control and shocked SR. In Langendorff hearts, shocks also decreased contractility and slowed relaxation. These data indicate that shocks with current densities similar to defibrillation depress Ca(2+)-pumping function of cardiac SR because of uncoupling of ATP hydrolysis and Ca2+ transport. Shock-induced impairment of Ca2+ pump function may underlie postshock myocardial dysfunction.
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PMID:Defibrillation depresses heart sarcoplasmic reticulum calcium pump: a mechanism of postshock dysfunction. 945 57


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