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)

Anoxia has been compared with ischaemia. The abrupt restoration of either oxygen of flow may accelerate cardiac damage. Anoxic stimulation of glycolysis (Pasteur effect) is inhibited during ischaemia by lactate and proton accumulation at the levels of phosphofructokinase and glyceraldehyde-3-phosphate dehydrogenase. Anaerobic glycolysis provides lactate and ATP; breakdown of the latter provides protons. During partial respiration thought to occur in partial ischaemia, continued production of CO2 is a factor contributing to intracellular acidosis; mitochondrial ATP when formed by continued respiration also yields protons when ultimately broken down. The endoproducts of aerobic glycolysis (pyruvate and NADH) are transported into the mitochondria by the malate-aspartate cycle and by pyruvate dehydrogenase activity. Adenine nucleotide transferase activity normally transfers the mitochondrially-made ATP to the cytoplasm, but acyl CoA accumulates in ischaemia (or during perfusions with high circulating free fatty acids) to inhibit the transferase. The mitochondrial creatine kinase is thought to transform ATP transported outwards into creatine phosphate which can permeate the outer mitochondrial membrane. Further compartmentation of ATP may be by other creatine kinase isoenzymes or in relation to the cell membrane. The glycogenolytic-sarcoplasmic reticulum complex links a glycogen pool to the sarcoplasmic reticulum. Cyclic AMP may regulate admission of calcium to the cell during the plateau of the action potential and promote calcium uptake by the sarcoplasmic reticulum by phosphorylation of phospholamban. The latter promotes the activity of the calcium-transport ATPase. Calcium and cyclic AMP may also interact at the level of the contractile proteins where cyclic AMP phosphrylates troponin. Cyclic GMP generally has opposite effects to cyclic AMP and undergoes opposite changes in the frog cardiac cycle to those of cyclic AMP. A present it is reasonable to suppose that physiological effects of adrenaline or of cholinergic agents on the myocardium are mediated by cyclic AMP or cyclic GMP, respectively, but this hypothesis still lacks firm support. There is an association between tissue cyclic AMP and ventricular fibrillation after coronary ligation, and direct evidence for a role of cyclic AMP in promoting arrhythmias has been obtained by studies on the ventricular fibrillation threshold in the rat heart. However, there are other mechanisms, involving first the effects of substrates on the action potential duration, and secondly, the fast channel, which can also give rise to the development of malignant arrhythmias.
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PMID:Myocardial metabolism and heart disease. 3 41

Effect of digitalis on central sympathetic neurons have been proposed to alter sympathetic influences on the heart and to contribute to the induction of arrhythmias. Recently, however, we have presented evidence which indicates that the involvement of a direct central action of digitalis is negligible in the alteration of sympathetic nerve activity after i.v. administration of the drug. Thus, a group of experiments were designed to determine if central drug concentrations or biochemical events in the brain would suggest a central action of the drug. Tritiated digoxin (20 microng/kg) was injected i.v. into cats every 15 minutes until ventricular fibrillation occurred. The concentrations of digoxin in cerebrospinal fluid and serum increased linearly with time as the cumulative dose of digoxin was increased. At the mean arrhythmic dose, 140 microng/kg, cerebrospinal fluid contained approximately 10 nM digoxin whereas free digoxin concentration in serum was approximately 30 nM and total digoxin concentration in serum was approximately 120 nM. Since inhibition of Na+,K+-adenosine triphosphatase (Na+,K+-ATPase) is often associated with the pharmacological effects of digitalis, effects of nanomolar concentrations of digoxin on Na+,K+-ATPase activity were determined in vitro. The concentration of digoxin faund in cerebrospinal fluid at arrhythmia inhibited Na+,K+-ATPase only slightly (5-10%). Activity of Na+,K+-ATP-ase was also examined in brains of cats which had died in ventricular arrhythmias due to treatment with lethal dose of digitoxin. After ventricular fibrillation, the cat brains were removed and Na+,K+-ATPase activity and ouabain binding were determined in eight areas. No reduction in Na+,K+-ATPase activity or [3H]ouabain binding was observed in any area. Thus, it appeared that toxic doses of digitalis did not cause sail to provide evidence for central effects of toxic doses of digoxin or digitoxin.
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PMID:Digitalis toxicity: lack of marked effect on brain na+,k+-adenosine triphosphatase in the cat. 13 66

4 patients tried to commit suicide by ingestion of 45 to 100 tablets of digoxin (Lanicor 0,25 mg) and acteyldigoxin (Novodigal 0,2 mg) respectively. In all patients cardiac arrhythmias occurred including 3 rd degree av-block, tachyarrhythmias and ventricular fibrillation which was lethal in two patients. After a short period hyperkaliaemia a rapid decrease of potassium in the serum was observed 3-12 hours after administration of digoxin. This loss of potassium was due to an increased excretion of potassium and sodium in the urine. It is thought that a reversible tubular leakage is responsible for the loss of electrolytes by the kidney rather than an inhibition of the ATPase in kidney tissue. From our observations the following therapy scheme for digitalis-intoxication is recommended: 1. Gastric lavage and administration of absorbents (charcoal, cholestyramin) in order to decrease the absorption of the glycosides and to interrupt the enterohepatic circulation. 2. Substitution of electrolytes by infusions and by oral route to balance sodium and potassium levels in the serum. 3. Administration of diphenylhydantoin for treatment of cardiac arrhythmias. 4. Implantation of a temporary pacemaker for treatment of cardiac arrhythmias especially for the management of bradycardias. 5. Plasmapheresis to lower the glycosid concentration in the heart muscle and in other tissues.
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PMID:[Treatment of severe digitalis-intoxication in suicidal attempt (author's transl)]. 114 71

The increase in intracellular sodium (Nai), resulting from inhibition of the Na/K ATPase by cardiac glycosides, is known to increase calcium influx via Na(+)-Ca2+ exchange, and thereby increase contractility. This increase in intracellular Ca2+ has been related to the development of intracellular acidification and enhanced activity of the Na(+)-H+ exchanger as a measure by the cell to prevent further acidification. Thus, the efflux of the H+ ions results in an additional increase in Nai. This may subsequently lead to an increased rate of Ca2+ influx and therefore to the potentiation of the effects of cardiac glycosides. To assess the role of Na(+)-H+ exchange in the mechanism of ouabain action in the beating heart we used amiloride, a known inhibitor of Na(+)-H+ exchange. Isolated rat hearts were perfused with either ouabain (50 microM) alone (n = 8, Group I), amiloride (1.0 mM) + ouabain (50 microM) (n = 8, Group II), or amiloride (1.0 mM) alone as a control group (n = 4, Group III). 23Na and 31P NMR spectroscopy were used to assess the changes in Nai and intracellular pH (pHi), respectively, while simultaneous and continuous monitoring of left ventricular pressure was carried out. Perfusion with both ouabain alone (Group I) or ouabain + amiloride (Group II), resulted in a time dependent increase in Nai levels, reaching (within 25 mins) a maximum of 200 +/- 7% of control in Group I, and 170 +/- 10% of control in Group II. Concurrently, a mild but significant decrease in pHi was observed in both groups. This decrease, however, was significantly higher in Group II compared to Group I (0.34 pH units vs. 0.19 pH units, respectively; P less than 0.05), suggesting that inhibition of Na(+)-H+ exchange by amiloride limits the recovery from ouabain-induced intracellular acidification. While developed pressure gradually increased in Group I to a maximum of 268 +/- 52% of control, the addition of amiloride in Group II substantially reduced the positive inotropic effect. Ventricular fibrillation (VF) developed in three of the eight hearts in Group I within 10-13 mins after the addition of ouabain. Interestingly, the rate of Nai increase in hearts that sustained VF was significantly higher compared to those without VF (mean slope 10.1 +/- 2.11 vs. 3.9 +/- 1.0, respectively; P less than 0.0001). Ventricular fibrillation did not develop in Group II or III.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Amiloride in ouabain-induced acidification, inotropy and arrhythmia: 23Na & 31P NMR in perfused hearts. 132 Jul 2

Effect of acute lethal blood loss on character and frequency of cardiac arrhythmias in postresuscitation period has been studied. Experiments were carried out on mongrel male rats resuscitated after 4- and 6-min clinical death caused by acute blood loss. Electric cardiac instability was found in early postresuscitation period. Pacemaker migration, paroxysmal ventricular tachycardia, blockades and extrasystole that lead to ventricular fibrillation were observed in 20 percent of cases. Supported by correlative analysis it has been established that the main arrhythmogenic factors are abundance of catecholamines, free fatty acids, dienic conjugates, lactate and inhibition of Ca dependent ATPase. Antiarrhythmogenic effects of antihypoxant gutimin, the beta-adrenoreceptor blocker inderal, antioxidant oxypiridin-6 were noticed after their separate administration before clinical death. The same effect of carnosine and phosphocreatine administered during resuscitation also was noticed.
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PMID:Pathogenesis and pharmacorrection of early postresuscitation cardiac arrhythmia. 132 77

High potassium solution is one of the most commonly used cardioplegic solution, but the mechanism of action is still poorly defined. In the present study, isolated rat hearts were utilized to investigate the protective effects and mechanism of action of high potassium against ischemia/reperfusion injury. The results showed that high potassium (22 mmol/L) apparently improved the recovery of contraction amplitude (P < 0.01), inhibited the rise of resting tension (P < 0.01) and abolished ventricular fibrillation during reperfusion after global ischemia for 40 minutes. Moreover, high potassium could preserve myocardial Na+, K(+)-ATPase activity (P < 0.01) and inhibit sodium and calcium overload (P < 0.01) during reperfusion. The results indicate that small amount of high potassium solution (5 ml) administered even after ischemic arrest of rat heart has remarkable protective effects against ischemia/reperfusion injury at 37 degrees C. Its mechanism of action is at least partially by preserving Na+,K(+)-ATPase activity and inhibiting sodium and calcium overload.
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PMID:[Protective effects of high potassium administered after ischemic arrest against reperfusion injury in isolated rat hearts]. 133 40

Isolated perfused rat heart model was used to observe the protective effects of berbamine on myocardial ischemia/reperfusion injury. The hearts were significantly 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, 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. 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:Mechanisms of protective effects of berbamine on ischemia/reperfusion injury in isolated rat heart. 133 20

The delayed effects of 7-oxo-prostacyclin, protecting the heart against extrasystoles, ventricular fibrillation, and cardiac arrest induced by high doses of ouabain or in ischemia and postischemic reperfusion, have already been described; but little is known about the molecular mechanisms involved. In this study, 50 micrograms.kg-1 7-oxo-prostacyclin administered intramuscularly significantly stimulated the activity of (Na+K+)-ATPase in rat heart sarcolemma 24 and 48 hours after application (p less than 0.01 and p less than 0.001, respectively). Kinetic analysis revealed a mixed type of stimulation of ATPase activity, with increased Vmax and decreased Km values. Cycloheximide (1 mg.kg-1) applied together with 7-oxo-prostacyclin, significantly antagonized the stimulatory effect of 7-oxo-prostacyclin, and had a modulatory effect on the kinetics of the (Na+K+)-ATPase both 24 and 48 hours after administration. The results show that protein synthesis is involved in the mechanism of the increase in enzyme activity.
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PMID:Increased activity of sarcolemmal (Na+K+)-ATPase is involved in the late cardioprotective action of 7-oxo-prostacyclin. 165 98

The effects of halothane and isoflurane anaesthesia on myocardial injury in rabbits subjected to coronary artery ligation and subsequent reperfusion were analyzed. Although halothane and isoflurane (at inspired concentrations of 1.0 and 1.5 per cent, respectively) exerted comparable effects on cardiovascular status during ischaemic and reperfusion phases, greater preservation of subcellular integrity (as assessed by mitochondrial and sarcoplasmic reticular ATPase activities and myocardial ionic alterations) and a lower incidence of ventricular fibrillation and severe hypotension occurred with halothane. Our results indicate that in studies of experimental myocardial ischaemia anaesthetics may, independently of cardiovascular actions, influence the nature and extent of resulting injury, possibly by virtue of their differing effects on subcellular membrane systems.
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PMID:Myocardial ischaemic/reperfusion injury in the anaesthetized rabbit: comparative effects of halothane and isoflurane. 294 79

This study was undertaken to characterize catecholamine-induced myocardial necrosis in 10-week alloxan-diabetic rabbits. Myocardial injury was induced by administering graded doses of isoproterenol (ISO) for 15 days. Injection of ISO to control and diabetic rabbits resulted in atrial tachycardias and ventricular fibrillation. The severity of the arrhythmias and the overall mortality was the same in both groups of animals. Analyses of serum biochemical parameters revealed significant increases in blood glucose, free fatty acids and total cholesterol in the ISO-treated diabetic animals relative to ISO-treated controls. ISO-treatment of both control and diabetic animals showed similar increases in heart weight, left ventricular weight and myocardial total water content. Analyses of various subcellular organelle marker enzyme activities indicated a significant decrease in the K+, Ca2+-stimulated sarcoplasmic reticulum, mitochondrial (azide-sensitive) and sarcolemmal Na+, K+-stimulated ATPase activities, decreases in ATP and glycogen and increases in myocardial sodium content in both the ISO-treated control and diabetic animal hearts. In addition, significant accumulation of Ca2+ and hydroxyproline were evident in the ISO-treated diabetic animal hearts.
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PMID:Isoproterenol-induced myocardial alterations in alloxan-diabetic rabbits. 302 4


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