Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac repolarisation depends mainly on the cellular extrusion of positive electrical charge related to the potassium ion through different channels. There are many potassium channels which are responsible for repolarisation in different cardiac tissues. Prolongation or shortening of the repolarisation period may be both antiarrhythmic and proarrhythmic depending on the given experimental conditions. Different potassium channels may be opened or blocked by clinically prescribed drugs. Activators of the iK(ATP) channels may exert antiarrhythmic effects by inhibiting activity induced by prolonged repolarisation. Experimentally, they may exert a proarrhythmic effect by predisposing to arrhythmias during myocardial ischemia. However, these effects have not been clearly demonstrated clinically. Potassium channel blockers may have an antiarrhythmic effect by reducing the variability of repolarisation, by prolonging the atrial and ventricular refractory periods and by their antifibrillatory actions. Nevertheless, they may have proarrhythmic effects resulting in triggered activation under particular conditions of bradycardia and/or ischemia. Examples of these effects have been reported in man. The understanding of the relationship between potassium channels and arrhythmias is particularly complex because of the multiple factors regulating the duration of repolarisation and the effects of drugs on this duration. These factors include the activity of the autonomic nervous system, the heart rate, ischemia and acidosis and the differences in response to endocardial and epicardial tissues.
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PMID:[Potassium channels and arrhythmia]. 130 98

Myocardial disease states are characterized by multiple electrophysiologic abnormalities, including alterations in potassium channel activities. During acute myocardial ischemia, activation of ATP-regulated K+ current (IK(ATP)) results in shortening of action potential duration and elevation of extracellular K+ concentration. In hypertrophied myocardium, increases in inward rectifier K+ current (IK1) and decreases in delayed rectifier K+ current (IK) are observed. Alterations in K+ channel activity in myocardial disease states suggest the potential to therapeutically modify cardiac rhythm and function with K+ channel modulators. Class III anti-arrhythmic agents, which prolong myocardial refractoriness predominantly via a blockade of IK, have demonstrated efficacy in suppressing reentrant atrial and ventricular arrhythmias in animal models as well as promising efficacy in initial clinical studies. Potassium channel openers (PCOs), which activate cardiac IK(ATP), have demonstrated both antiarrhythmic and proarrhythmic activities in various experimental settings, and also are being investigated as potential cardioprotective agents. Sulfonylureas, which block cardiac IK(ATP), also have been investigated as potential antiarrhythmic agents with equivocal results, and have displayed a propensity to exacerbate ischemic myocardial dysfunction in experimental studies. A more comprehensive understanding of K+ channel activity in various myocardial disease states, including concomitant disorders such as myocardial ischemia and hypertrophy, will facilitate the development of more useful potassium channel modulators, as well as a clearer recognition of the undesirable effects of such agents.
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PMID:Therapeutic potential of modulating potassium currents in the diseased myocardium. 138 85

During acute myocardial ischemia, passage of potassium ions across the sarcolemma to the extracellular space is a well-established phenomenon. A recent hypothesis is that the ATP-dependent potassium channel plays a role in contributing to the potassium loss. As the potassium loss starts while the overall level of ATP is still relatively high, and as the channel is inhibited by rather low concentrations of ATP, the question arises as to how the channel is opened. Among the proposals are that, in addition to the total concentration of ATP, there is modulation of the regulation by its breakdown products, such as ADP and adenosine. Alternatively, or in addition, breakdown products of anaerobic glycolysis, such as lactate and protons, may also play a role. Extracellular acidosis may help to activate the channel, and internal lactate accumulation may have a similar effect. In certain circumstances there is evidence that ATP produced by glycolysis plays a significant role in the control of potassium channel activity. The concept of subsarcolemmal ATP is another explanation for the activation of the channel at relatively high ATP concentrations. Potassium channel closing drugs, such as glibenclamide, may prolong the action potential duration (shortened by ischemia) and thereby decrease the incidence of early ventricular arrhythmias. This same category of drugs may reduce early potassium loss from the ischemic tissue, thereby lessening the potentially protective effect of the external accumulation of potassium on the ischemic zone, the so-called local cardioplegic effect. Conversely, drugs of the potassium channel activating group are likely to have opposite effects on these arrhythmias and on myocardial protection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of ischemia by regulation of the ATP-sensitive potassium channel. 825 20

Decreasing heart rate is potentially useful in ischaemic heart disease. Tedisamil is a bradycardic agent resulting from its ability to inhibit transient outward current (I(to)) in atria. Tedisamil inhibits I(to), potassium current (IK), K(ATP) and the protein kinase A-activated chloride channel in ventricles as well as vascular IK and Ca(2+)-activated IK (IK((Ca))). Tedisamil prolongs cardiac action potentials and the corrected QT (QTc) of the ECG and also increases cardiac refractoriness. Tedisamil is anti-arrhythmic in animal models of ventricular arrhythmias and atrial flutter. The bradycardic effect of tedisamil is associated with a reduction in myocardial oxygen demand. On isolated rat ventricle, tedisamil is a positive inotrope and on isolated rabbit atria, tedisamil reverses the negative inotropic effect of pinacidil. Tedisamil contracts the isolated rat portal vein and aorta, reduces cromakalim-induced relaxations of contracted rat aorta and increases blood pressure in animals and humans. Tedisamil is 96% bound to plasma proteins, has a plasma half-life of about 10 h and is cleared from the kidney unchanged. Clinical trials have shown that the electrophysiology of tedisamil is that of a class III anti-arrhythmic. In coronary artery disease, tedisamil has no effect on inotropism and increases the threshold for angina. Potassium channel blockade with tedisamil may have advantages over calcium channel blockers or K(ATP) channel openers as an anti-ischaemic mechanism in coronary artery disease. In exercise-induced myocardial ischaemia, beta-blockers are probably favourable to tedisamil, as they will limit the increase in heart rate, contractility and blood pressure caused by sympathetic stimulation, whereas tedisamil will not. In heart failure patients, tedisamil reduces heart rate, but increases blood pressure. The usefulness of tedisamil as a bradycardic agent is limited by the increase in blood pressure. A drug that is bradycardic without increasing blood pressure would be an improvement on tedisamil as the master switch of nature for ischaemic heart disease.
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PMID:Tedisamil: master switch of nature? 1111 86