Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042510 (ventricular fibrillation)
 10,091 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

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

The effects of KB-R7943 (2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate) on major ion transporters were studied in canine cardiac sarcolemmal and sarcoplasmic reticular vesicles. KB-R7943 inhibited the Na+/Ca2+ exchange more potently than the Na+/H+ exchange, the Na+/K(+)-ATPase and the Ca2(+)-ATPase. The effects of KB-R7943 on ischemia/reperfusion-induced injury were studied in isolated rat perfused hearts in comparison with those of diltiazem and lidocaine. In normal hearts, diltiazem (10 microM) and lidocaine (100 microM) markedly reduced contractile function, but KB-R7943 (1, 10 microM) had no such effect. In the hearts subjected to 25-min ischemia and 30-min reperfusion, KB-R7943 concentration-dependently and significantly improved post-ischemic recovery of left ventricular developed pressure, left ventricular dP/dtmax and left ventricular end-diastolic pressure by pre-ischemic treatment (5 min) or post-ischemic treatment (10 min). Diltiazem and lidocaine showed similar improvement of recovery by pre-ischemic treatment, but they had no effect by post-ischemic treatment. Furthermore, the effect of KB-R7943 on arrhythmia was studied in anesthetized rats subjected to 5-min cardiac ischmeia and 10-min reperfusion. KB-R7943 (1, 10 mg/kg, i.v.) dose-dependently reduced the incidence and the duration of ventricular fibrillation. These results indicate that KB-R7943, a selective Na+/Ca2+ exchange inhibitor, has beneficial effects against myocardial ischemia/reperfusion injury and suggest that activation of the Na+/Ca2+ exchange mainly occurs immediately after reperfusion in the pathophysiological process of myocardial ischemia/reperfusion injury.
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PMID:[Effects of KB-R7943, a novel Na+/Ca2+ exchange inhibitor, on myocardial ischemia/reperfusion injury]. 955 49

Oleander, a flowering plant that grows in the Mediterranean and southern US, contains the cardiac glycosides oleandrin, digitoxigenin and nerium, which inhibit Na(+)-K+ ATPase. Clinical manifestations of oleander toxicity include gastrointestinal irritation, marked hyperkalemia, A-V block, ventricular dysrhythmia, and not uncommonly death. Because fructose-1,6-diphosphate (FDP) has been shown to attenuate digoxin toxicity, we determined whether this agent would be effective in the treatment of the toxicity of these similarly-structured cardiac glycosides. Anesthetized dogs (n = 12) were infused i.v. for 5 min with 40 mg oleander extract/kg and then 6 dogs randomly selected from that group received a 50 mg/kg bolus of 10% FDP followed by a constant infusion. The other control animals received the same dosage of 10% dextrose. Within 5 min after oleander administration, all dogs developed dysrhythmias. The FDP-treated animals reverted to sinus rhythm within 1.58 +/- 0.15 h; none in the control group returned to sinus rhythm. One control dog died at 3 h from ventricular fibrillation. Marked hyperkalemia was observed in the control group; plasma K+ remained unchanged in the FDP group. Throughout the 4 h experimental period the FDP group maintained normal arterial pressures; in the control dextrose group, pressures were profoundly depressed. Cardiac output declined in both groups but remained higher in the FDP group. To determine the mechanism whereby FDP attenuates oleander toxicity, we studied the in vitro effect of FDP on oleander poisoned myocardial sarcolemmal membranes. At concentrations of 1 and 2 mg oleander inhibited Na(+)-K+ ATPase activity and addition of 500 microM FDP restored myocardial sarcolemmal Na(+)-K+ ATPase function. FDP effectively prevented hyperkalemia, reversed dysrhythmias and improved hemodynamics in vivo in this canine model of oleander toxicity and also restored sarcolemmal Na(+)-K+ ATPase activity in vitro.
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PMID:Fructose-1,6-diphosphate in the treatment of oleander toxicity in dogs. 994 76

Digoxin inhibits the membrane-bound ATPase enzyme, resulting in a rise in intracellular sodium and activated outward potassium current, predisposing to arrhythmias. In this study, the effect of ketanserin, thought to block outward potassium currents, was investigated on digoxin-induced arrhythmias. Twenty-four guinea-pigs were studied in four groups (control, ketanserin 0.5 mg/kg, ketanserin 1 mg kg, ketanserin 2 mg/kg). Under pentobarbital anaesthesia (40 mg/kg), 15 min after injection of saline or ketanserin, digoxin (0.6 mg/kg) was administered through the jugular vein. Carotid artery blood pressure and electrocardiogram (ECG) were recorded. The time for the onset of the first arrhythmia and incidence of ventricular tachycardia (VT), ventricular fibrillation (VF), and premature ventricular contraction (PVC) were determined. Arrhythmias were scored according to the MacLeod scale. Ketanserin produced minor haemodynamic effects and lacked, by itself, arrhythmogenic effects at the doses studied. However, it increased the time for the onset of the first digoxin-induced arrhythmia and decreased the incidence of VT, VF and PVC. We conclude that ketanserin inhibits digoxin-induced arrhythmias in guinea-pigs.
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PMID:Ketanserin inhibits digoxin-induced arrhythmias in the anaesthetized guinea-pig. 1062 51

Abnormal intracellular Ca(2+) cycling plays an important role in cardiac dysfunction and ventricular arrhythmias in the setting of heart failure and transient cardiac ischemia followed by reperfusion (I/R). We hypothesized that overexpression of the sarcoplasmic reticulum Ca(2+) ATPase pump (SERCA2a) may improve both contractile dysfunction and ventricular arrhythmias. Continuous ECG recordings were obtained in 46 conscious rats after adenoviral gene transfer of either SERCA2a or the reporter gene beta-galactosidase (beta gal) or parvalbumin (PV), as early as 48 h before and 48 h after 30 min ligation of the left anterior descending artery by using an implantable telemetry system. Sham-operated animals were used for comparison for hemodynamic measurements, whereas within-animal baseline was used for electrocardiographic and echocardiographic parameters. All episodes of nonsustained ventricular tachycardia (VT) and ventricular fibrillation (VF) were counted, and their durations were summed by telemetry. I/R decreased regional cardiac wall thickening as well as the maximal rate of left ventricular pressure rise (+dP/dt) and ventricular pressure fall (-dP/dt). SERCA2a restored regional wall thickening and +dP/dt and -dP/dt to levels seen preoperatively. Regional-wall motion and anterior-wall thickening were improved in the SERCA2a animals, as assessed by echocardiography and piezoelectric crystals. To assess whether these effects are SERCA2a specific, we overexpressed a skeletal-muscle protein, PV, to examine whether Ca(2+) buffering alone can mitigate ventricular arrhythmias. During the first hour after I/R, the rate of nonsustained VT plus VF was 16 +/- 5 episodes per h (n = 6) in the Ad.beta gal group, 22 +/- 6 in the Ad.PV group, and 4 +/- 2(n = 6, P < 0.01) in the Ad.SERCA2a group. The decrease in VT plus VF in the Ad.SERCA2a group was consistent throughout the 48 h of monitoring. These results show that improving intracellular Ca(2+) handling by overexpression of SERCA2a restores contractile function and reduces ventricular arrhythmias during I/R.
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PMID:Abrogation of ventricular arrhythmias in a model of ischemia and reperfusion by targeting myocardial calcium cycling. 1507 64


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