Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cardiac arrhythmias cause more than 300,000 sudden deaths each year in the USA alone. Long QT syndrome (LQT) is a cardiac disorder that causes sudden death from ventricular tachyarrhythmias, specifically torsade de pointes. Four LQT genes have been identified: KVLQT1 (LQT1) on chromosome 11p15.5, HERG (LQT2) on chromosome 7q35-36, SCN5A (LQT3) on chromosome 3p21-24, and MinK (LQT5) on chromosome 21q22. SCN5A encodes the cardiac sodium channel, and LQT-causing mutations in SCN5A lead to the generation of a late phase of inactivation-resistant whole-cell inward currents. Mexiletine, a sodium channel blocker, is effective in shortening the QT interval corrected for heart rate (QTc) of patients with SCN5A mutations. HERG encodes the cardiac I(Kr) potassium channel. Mutations in HERG act by a dominant-negative mechanism or by a loss-of-function mechanism. Raising the serum potassium concentration can increase outward HERG potassium current and is effective in shortening the QTc of patients with HERG mutations. KVLQT1 is a cardiac potassium channel protein that interacts with another small potassium channel MinK to form the cardiac I(Ks) potassium channel. Like HERG mutations, mutations in KVLQT1 and MinK can act by a dominant-negative mechanism or a loss-of-function mechanism. An effective treatment for LQT patients with KVLQT1 or MinK mutations is expected to be developed based on the functional characterization of the I(Ks) potassium channel. Genetic testing is now available for some patients with LQT.
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PMID:Genetics, molecular mechanisms and management of long QT syndrome. 955 90

Cardiac disorders are observed when excessive plasma concentrations of local anaesthetics are reached, following for instance intravascular accidental injection for epidural anaesthesia or brachial plexus block. Bupivacaine particularly, which is one of the most used local anaesthetics, adversely affects intraventricular conduction and cardiac contractile strength from the 3.0-4.0 micrograms/ml blood levels. Depression of conduction is especially to be feared, for it can result in reentrant arrhythmias likely to degenerate into often fatal ventricular fibrillation. Such accidents may sometimes occur at far lower concentrations, subsequent to diffusion into systemic circulation from the injection site (0.4-1.2 micrograms/ml). These accidents were probably due to various factors which concomitantly intervene during the anaesthesia. We could identify a number of these factors by associating them to an intravenous infusion of bupivacaine (0.04 mg/kg/min after a loading dose of 1.00 mg/kg) in animals (dogs and pigs) under electrocardiographic monitoring, in which conduction time, monophasic action potential duration, effective refractory period and electrical fibrillation threshold were determined in the ventricular fibres. The electrophysiological changes due to bupivacaine may be enhanced by 1) dilution hyponatremia (115-110 mmol/l) induced by a short (5 min) intravenous 10 ml/kg/min infusion of hypotonic solution and/or hyperkalemia (7-8 mmol/l) induced by 0.05 mmol/kg/min infusion of potassium chloride; 2) the acceleration of cardiac contractions (180-210 beats/min) induced by ventricular pacing; 3) mild hypothermia (35-34 degrees C) induced by blood cooling in an extracorporeal circuit; 4) myocardial ischaemia induced by complete temporary occlusion of the left anterior descending coronary artery near its origin. The risk of cardiac accidents, possibly severe, is therefore enhanced by each of these factors capable of lowering the concentration required for their triggering and, of course, the combination of two or several of them. On the contrary, the knowledge of these factors should allow to prevent most of cardiac accidents of locoregional anaesthesia.
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PMID:[Cardiac accidents of locoregional anesthesia: experimental study of risk factors with bupivacaine]. 964 39

Most arrhythmias occur in patients with structural heart disease, where anatomical factors play an important role. Patients without structural heart disease may also suffer from arrhythmias, and recently the genetic basis for such so-called idiopathic arrhythmias has been elucidated. In the congenital long QT syndrome, characterized by a prolonged QT interval, torsade de pointes and sudden death, three aberrant ionic currents have been identified, resulting in a prolongation of the ventricular action potential, which in its turn may cause early afterdepolarization and torsade de pointes. In LQTS1, mutations in the KvLQT1 gene reduce the slow component of the delayed rectifier Iks; in LQTS, mutations in the Human Ether a-go-go Related Gene (HERG) reduce the rapid component of the delayed rectifier Iks. Both potassium currents are important determinants of repolarization: a reduction in outward currents carried by K+ ions prolongs the action potential. In LQTS3, there are mutation in the NA+ channel gene (SCN5A) which causes the channel to inactivate incompletely; the persistent inward current carried by Na+ ions also prolongs the action potential. In the Brugada syndrome, characterized by right bundle branch block, ST elevation in V1-V3 and sudden death, mutations have been observed in the Na+ channel gene, but it is as yet unclear which functional changes in the NA+ channel are responsible for the typical ECG changes and the arrhythmias. Various cardiac disorders may lead to changes in gene expression that modify channel function. In hypertrophy, the ventricular action potential is prolonged by a decrease in the inward rectifier and the transient outward current. After prolonged episodes of rapid electrical activity, the atrial action potential is shortened, because of a reduction in the Iks type calcium current. Finally, many carriers of mutated genes display no abnormalities on the ECG. It is conceivable that such individuals may show excessive QT prolongation when taking cardiac or noncardiac drugs (such as neuroleptics, antidepressants, antihistamines, antimicrobials, antimalarials) that block potassium currents.
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PMID:Molecular mechanisms of arrhythmias. 983 81

Although prostate cancer is the number one diagnosed cancer in men, the importance of emphasizing and preventing other common diseases after diagnosis is essential. For example, heart disease still remains the number one cause of mortality in men, accounting for 50% of the deaths in Western countries. Therefore, promoting overall healthy behaviors also seems essential, especially in light of past and recent evidence that an individual can maintain proper health by following some simple guidelines. The increased consumption of healthy foods, greater intakes of B-vitamins and minerals such as potassium can significantly reduce the risk of heart disease, stroke, and possibly cancer in a patient with a prior or current malignancy. Overall dietary change as observed from the Mediterranean diet, light exercise, and improved mental health should also be stressed to the patient because of recent studies.
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PMID:Emphasizing and promoting overall health and nontraditional treatments after a prostate cancer diagnosis. 1033 26

Paroxysmal atrial fibrillation is defined as an atrial fibrillation that terminates spontaneously. It is desirable that atrial fibrillation should be terminated immediately after onset, and should be prevented from re-initiation to avoid atrial electrical remodeling or atrial stunning after cardioversion. Antiarrhythmic agents are used for these reasons. The important factors for pharmacological cardioversion of atrial fibrillation are thought to be prolongation of atrial refractory and suppression of conduction time in the atrium. Therefore, class Ia and Ic antiarrhythmic drugs, including bepridil as class IV because of its characteristics of class Ia, are administered to restore sinus rhythm. Verapamil and diltiazem, or beta adrenergic blocker, or digitalis decreases the ventricular response during atrial fibrillation for disturbance of atrioventricular nodal conduction, and then cardioversion of atrial fibrillation may occur. Suppression of supraventricular extrasystoles and atrial conduction time, or prolongation of atrial refractoriness will be needed to maintain sinus rhythm. Class I, III, or bepridil as class IV excepting lidocaine and mexiletine are used to prevent paroxysmal atrial fibrillation. In general, sodium channel blocker is superior for defibrillation and potassium channel blocker is superior for prophylaxis of atrial fibrillation. Considering efficacy, antiarrhythmic agents should be selected depending on the following factors: cardiac function, renal or hepatic function, underlying heart disease, exercise-induced or enhanced mental condition, cholinergic induced, drug-resistant atrial fibrillation or not.
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PMID:[Pharmacological restoration and maintenance of sinus rhythm by antiarrhythmic agents]. 1034 38

Most people with the Metabolic Syndrome die from thrombotic complications superimposed to degenerative arterial vascular lesions, mostly myocardial infarction. Type-2-Diabetes is a risk factor per se for such complications, but often clusters with dyslipoproteinemia, hypertension and obesity. This is referred to as "Metabolic Syndrome" and often operates on a genetically programmed susceptibility which accelerates the pathogenesis of coronary artery disease in front of a much wider diabetes specific cardiopathy. From a pathophysiological point of view none of these associated risk factors explains the pathogenetic series of events leading to the precipitation of an occlusive thrombus at sites of complicated coronary plaques. In patients with the Metabolic Syndrome the coagulation system is switched towards a prethrombotic state, involving increased plasmatic coagulation, diminished fibrinolysis, decreased endothelial thromboresistance and predominantly platelet hyperreactivity ("diabetic thrombocytopathy"). Some of these factors are associated with an increased coronary risk (e.g. fibrinogen, PAI-1, platelets), but are also directly linked to the pathogenesis of "atherothrombosis". Altered cardiac remodelling together with adhesion and coagulation mechanisms appears suitable to explain decreased functional performance of infarcted organs, decreased success of acute (reduced fibrinolytic response, no reflow phenomenon) and longterm intervention strategies for vessel patency (PTCA, CABG) in Diabetes. Glucose adjustment alone will not adequately neutralize these complex mechanisms, but in the situation of myocardial infarction eumetabolization with parenteral glucose-insulin-potassium infusion appears mandatory similar to non-diabetics. On the longterm a multidimensional interventional repertoire is required particularly in patients with the Metabolic Syndrome including antihypertensive, antidyslipoproteinemic and antithrombotic drugs, customized according to the individual patients needs as assessed by early diagnostic measures ("early secondary prevention").
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PMID:[The heart and metabolic syndrome]. 1035 72

There exist gender differences in the frequency of the various forms of cardiac arrhythmias. Atrial fibrillation is more common in man in whom it is often a complication of coronary heart disease. Numerous elderly women however present with this rhythm disorder which is often a complication of congestive heart failure or valvular heart disease. Atrial fibrillation carries a high risk of cerebro-vascular embolic accident in female. Symptomatic supraventricular tachycardia and the long QT syndrome, inherited or acquired, are more frequent among women. The latter are also particularly susceptible to develop torsade de pointe as a consequence of therapy with drugs interfering with the potassium ion channels. Sudden cardiac death is more frequent in men than in women even when the latter suffer from coronary heart disease. Sudden cardiac death without structural heart disease is however more frequently seen in women. Nulliparity, tobacco use and alcoholism might be specific risk factors for sudden cardiac death in female. Cardiac arrhythmias may be seen during pregnancy. New onset or aggravated supraventricular tachycardia may be encountered during that period. Ventricular tachycardia in the absence of structural heart disease may also be seen during pregnancy. The treatment of cardiac arrhythmias in pregnant woman remains a challenge for the practising cardiologist.
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PMID:[Cardiac arrhythmias in women]. 1038 66

Numerous experimental, epidemiological and clinical studies have pointed out a relevant role for magnesium deficiency in the development of many cardiovascular diseases. Some pharmacological treatments may interfere with magnesium turnover, and magnesium deficiency may alter the pharmacokinetics and pharmacodynamics of some cardiovascular drugs. Loop and thiazide-like diuretics increase magnesiuresis, and total bodily magnesium deficiency may appear during prolonged treatment with diuretically active doses of these drugs. The potassium retaining agents, such as amiloride, triamterene and spironolactone, tend to retain magnesium but they are not magnesium-retaining substances to the extent to which they are potassium-retaining diuretics. The interaction between magnesium and digitalis is complex. Magnesium, acting as an indirect antagonist of digoxin at the sarcolemma Na(+)-K(+)-ATPase pump, reduces cardiac arrhythmias due to digoxin poisoning. Recent controlled studies have shown that treatment with magnesium significantly reduces the frequency and complexity of ventricular arrhythmias in digoxin-treated patients with congestive heart failure without digoxin toxicity. Magnesium improves the efficacy of digoxin in slowing the ventricular response in atrial fibrillation. Digoxin reduces tubular magnesium reabsorption, and in patients with congestive heart failure this interaction may be cumulative with other causes of magnesium deficiency (diuretics, diet, poor intestinal absorption). The complex and potentially life-threatening interactions between magnesium and some cardiovascular drugs suggest that magnesium status should be carefully monitored in patients receiving such drugs. Therapy with magnesium is rapidly acting, has a safe toxic-therapeutic ratio, is easy to administer and titrate. The correction of magnesium deficit should therefore always be considered for patients with cardiopathy.
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PMID:Magnesium and cardiovascular drugs: interactions and therapeutic role. 1052 23

In our review (Law & Morris, 1998), we presented analyses of data from 10 cohort studies yielding the summary estimate that the risk of ischaemic heart disease was 15% lower at the 90th than at the 10th centile of fruit and vegetable consumption. This 10th-90th centile difference in consumption is a realistic increase for an individual (Zino et al, 1997). The estimate of a 15% difference in heart disease mortality was similar to the expected difference in risk from the increase in potassium consumption (given the corresponding decrease in blood pressure) and the increase in folate consumption (given the corresponding decrease in plasma homocysteine) that would result from this specified increase in fruit and vegetable consumption. Ness and colleagues' own approach to such a review was to tabulate the studies with their methodological details and list the result of each study as showing 'no association' or 'protective effect' (Ness & Powles, 1997), when the evidence did not justify the implicit dichotomy. Associations were reproduced as published, in different formats for different studies, and confidence intervals commonly not reported. This left the reader with little impression of the average size of the association nor the degree of consistency between studies. Ness and colleagues express disapproval of our quantitative approach but provide no sound basis for rejecting it. We believe that our results are valid, and that the quantification of the effect is useful in establishing for the first time the moderate but important reduction in heart disease risk that results from a realistic increase in fruit and vegetable consumption. The main argument of Ness and colleagues is that estimates of effect derived from cohort studies are unreliable. We respond to this first, and then to four methodological issues that they raise.
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PMID:By how much does fruit and vegetable consumption reduce the risk of ischaemic heart disease: response to commentary 1055 6

Amiodarone is the most promising drug in the treatment of life-threatening ventricular tachyarrhythmias in patients with significant structural heart disease. The pharmacologic profile of amiodarone is complex and much remains to be clarified about its short- and long-term actions on multiple molecular targets. This article reviews electrophysiologic effects of amiodarone based on previous reports and our own experiments in single cells and multicellular tissue preparations of mammalian hearts. As acute effects, amiodarone inhibits both inward and outward currents. The inhibition of inward sodium and calcium currents (I(Na), I(Ca)) is enhanced in a use- and voltage-dependent manner, resulting in suppression of excitability and conductivity of cardiac tissues especially when stimulated at higher frequencies and in those with less-negative membrane potential. Both voltage- and ligand-gated potassium channel currents (I(K), I(K,Na), I(K,ACh)) are also inhibited at therapeutic levels of drug concentrations. Acutely-administered amiodarone has no consistent effect on the action potential duration (APD). The major and consistent long-term effect of the drug is a moderate APD prolongation with minimal frequency dependence. This prolongation is most likely due to a decrease in the current density of I(K) and I(to). Chronic amiodarone was shown to cause a down-regulation of Kv1.5 messenger ribonucleic acid (mRNA) in rat hearts, suggesting a drug-induced modulation of potassium-channel gene expression. Tissue accumulation of amiodarone and its active metabolite (desethylamiodarone) may modulate the chronic effects, causing variable suppression of excitability and conductivity of the heart through the direct effects of the compounds retained at the sites of action. Amiodarone and desethylamiodarone could antagonize triiodothyronine (T3) action on the heart at cellular or subcellular levels, leading to phenotypic resemblance of long-term amiodarone treatment and hypothyroidism.
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PMID:Amiodarone: ionic and cellular mechanisms of action of the most promising class III agent. 1056 56


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