Arrhythmias, Cardiac: Any disturbances of the normal rhythmic beating of the heart or MYOCARDIAL CONTRACTION. Cardiac arrhythmias can be classified by the abnormalities in HEART RATE, disorders of electrical impulse generation, or impulse conduction.Arrhythmia, Sinus: Irregular HEART RATE caused by abnormal function of the SINOATRIAL NODE. It is characterized by a greater than 10% change between the maximum and the minimum sinus cycle length or 120 milliseconds.Electrocardiography: Recording of the moment-to-moment electromotive forces of the HEART as projected onto various sites on the body's surface, delineated as a scalar function of time. The recording is monitored by a tracing on slow moving chart paper or by observing it on a cardioscope, which is a CATHODE RAY TUBE DISPLAY.Tachycardia, Ventricular: An abnormally rapid ventricular rhythm usually in excess of 150 beats per minute. It is generated within the ventricle below the BUNDLE OF HIS, either as autonomic impulse formation or reentrant impulse conduction. Depending on the etiology, onset of ventricular tachycardia can be paroxysmal (sudden) or nonparoxysmal, its wide QRS complexes can be uniform or polymorphic, and the ventricular beating may be independent of the atrial beating (AV dissociation).Anti-Arrhythmia Agents: Agents used for the treatment or prevention of cardiac arrhythmias. They may affect the polarization-repolarization phase of the action potential, its excitability or refractoriness, or impulse conduction or membrane responsiveness within cardiac fibers. Anti-arrhythmia agents are often classed into four main groups according to their mechanism of action: sodium channel blockade, beta-adrenergic blockade, repolarization prolongation, or calcium channel blockade.Ventricular Fibrillation: A potentially lethal cardiac arrhythmia that is characterized by uncoordinated extremely rapid firing of electrical impulses (400-600/min) in HEART VENTRICLES. Such asynchronous ventricular quivering or fibrillation prevents any effective cardiac output and results in unconsciousness (SYNCOPE). It is one of the major electrocardiographic patterns seen with CARDIAC ARREST.Ventricular Premature Complexes: A type of cardiac arrhythmia with premature contractions of the HEART VENTRICLES. It is characterized by the premature QRS complex on ECG that is of abnormal shape and great duration (generally >129 msec). It is the most common form of all cardiac arrhythmias. Premature ventricular complexes have no clinical significance except in concurrence with heart diseases.Heart Conduction System: An impulse-conducting system composed of modified cardiac muscle, having the power of spontaneous rhythmicity and conduction more highly developed than the rest of the heart.Tachycardia: Abnormally rapid heartbeat, usually with a HEART RATE above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.Electrocardiography, Ambulatory: Method in which prolonged electrocardiographic recordings are made on a portable tape recorder (Holter-type system) or solid-state device ("real-time" system), while the patient undergoes normal daily activities. It is useful in the diagnosis and management of intermittent cardiac arrhythmias and transient myocardial ischemia.Cardiac Complexes, Premature: A group of cardiac arrhythmias in which the cardiac contractions are not initiated at the SINOATRIAL NODE. They include both atrial and ventricular premature beats, and are also known as extra or ectopic heartbeats. Their frequency is increased in heart diseases.Death, Sudden, Cardiac: Unexpected rapid natural death due to cardiovascular collapse within one hour of initial symptoms. It is usually caused by the worsening of existing heart diseases. The sudden onset of symptoms, such as CHEST PAIN and CARDIAC ARRHYTHMIAS, particularly VENTRICULAR TACHYCARDIA, can lead to the loss of consciousness and cardiac arrest followed by biological death. (from Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 7th ed., 2005)Long QT Syndrome: A condition that is characterized by episodes of fainting (SYNCOPE) and varying degree of ventricular arrhythmia as indicated by the prolonged QT interval. The inherited forms are caused by mutation of genes encoding cardiac ion channel proteins. The two major forms are ROMANO-WARD SYNDROME and JERVELL-LANGE NIELSEN SYNDROME.Atrial Fibrillation: Abnormal cardiac rhythm that is characterized by rapid, uncoordinated firing of electrical impulses in the upper chambers of the heart (HEART ATRIA). In such case, blood cannot be effectively pumped into the lower chambers of the heart (HEART VENTRICLES). It is caused by abnormal impulse generation.Tachycardia, Supraventricular: A generic expression for any tachycardia that originates above the BUNDLE OF HIS.Heart Rate: The number of times the HEART VENTRICLES contract per unit of time, usually per minute.Electrophysiologic Techniques, Cardiac: Methods to induce and measure electrical activities at specific sites in the heart to diagnose and treat problems with the heart's electrical system.Atrial Flutter: Rapid, irregular atrial contractions caused by a block of electrical impulse conduction in the right atrium and a reentrant wave front traveling up the inter-atrial septum and down the right atrial free wall or vice versa. Unlike ATRIAL FIBRILLATION which is caused by abnormal impulse generation, typical atrial flutter is caused by abnormal impulse conduction. As in atrial fibrillation, patients with atrial flutter cannot effectively pump blood into the lower chambers of the heart (HEART VENTRICLES).Defibrillators, Implantable: Implantable devices which continuously monitor the electrical activity of the heart and automatically detect and terminate ventricular tachycardia (TACHYCARDIA, VENTRICULAR) and VENTRICULAR FIBRILLATION. They consist of an impulse generator, batteries, and electrodes.Catheter Ablation: Removal of tissue with electrical current delivered via electrodes positioned at the distal end of a catheter. Energy sources are commonly direct current (DC-shock) or alternating current at radiofrequencies (usually 750 kHz). The technique is used most often to ablate the AV junction and/or accessory pathways in order to interrupt AV conduction and produce AV block in the treatment of various tachyarrhythmias.Heart Ventricles: The lower right and left chambers of the heart. The right ventricle pumps venous BLOOD into the LUNGS and the left ventricle pumps oxygenated blood into the systemic arterial circulation.Heart: The hollow, muscular organ that maintains the circulation of the blood.Cardiac Pacing, Artificial: Regulation of the rate of contraction of the heart muscles by an artificial pacemaker.Flecainide: A potent anti-arrhythmia agent, effective in a wide range of ventricular and atrial ARRHYTHMIAS and TACHYCARDIAS.Ventricular Dysfunction: A condition in which HEART VENTRICLES exhibit impaired function.Torsades de Pointes: A malignant form of polymorphic ventricular tachycardia that is characterized by HEART RATE between 200 and 250 beats per minute, and QRS complexes with changing amplitude and twisting of the points. The term also describes the syndrome of tachycardia with prolonged ventricular repolarization, long QT intervals exceeding 500 milliseconds or BRADYCARDIA. Torsades de pointes may be self-limited or may progress to VENTRICULAR FIBRILLATION.NAV1.5 Voltage-Gated Sodium Channel: A voltage-gated sodium channel subtype that mediates the sodium ion PERMEABILITY of CARDIOMYOCYTES. Defects in the SCN5A gene, which codes for the alpha subunit of this sodium channel, are associated with a variety of CARDIAC DISEASES that result from loss of sodium channel function.Dogs: The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065)Electric Countershock: An electrical current applied to the HEART to terminate a disturbance of its rhythm, ARRHYTHMIAS, CARDIAC. (Stedman, 25th ed)Amiodarone: An antianginal and class III antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting POTASSIUM CHANNELS and VOLTAGE-GATED SODIUM CHANNELS. There is a resulting decrease in heart rate and in vascular resistance.Action Potentials: Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli.Myocardium: The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.Heart Atria: The chambers of the heart, to which the BLOOD returns from the circulation.Myocytes, Cardiac: Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).Digitalis Glycosides: Glycosides from plants of the genus DIGITALIS. Some of these are useful as cardiotonic and anti-arrhythmia agents. Included also are semi-synthetic derivatives of the naturally occurring glycosides. The term has sometimes been used more broadly to include all CARDIAC GLYCOSIDES, but here is restricted to those related to Digitalis.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (CORONARY ARTERY DISEASE), to obstruction by a thrombus (CORONARY THROMBOSIS), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (MYOCARDIAL INFARCTION).Bradycardia: Cardiac arrhythmias that are characterized by excessively slow HEART RATE, usually below 50 beats per minute in human adults. They can be classified broadly into SINOATRIAL NODE dysfunction and ATRIOVENTRICULAR BLOCK.Models, Cardiovascular: Theoretical representations that simulate the behavior or activity of the cardiovascular system, processes, or phenomena; includes the use of mathematical equations, computers and other electronic equipment.Aconitine: A C19 norditerpenoid alkaloid (DITERPENES) from the root of ACONITUM plants. It activates VOLTAGE-GATED SODIUM CHANNELS. It has been used to induce ARRHYTHMIAS in experimental animals and it has antiinflammatory and antineuralgic properties.Myocardial Infarction: NECROSIS of the MYOCARDIUM caused by an obstruction of the blood supply to the heart (CORONARY CIRCULATION).Death, Sudden: The abrupt cessation of all vital bodily functions, manifested by the permanent loss of total cerebral, respiratory, and cardiovascular functions.Tropaeolaceae: A plant family of the order Geraniales, subclass Rosidae, class Magnoliopsida.Atrial Premature Complexes: A type of cardiac arrhythmia with premature atrial contractions or beats caused by signals originating from ectopic atrial sites. The ectopic signals may or may not conduct to the HEART VENTRICLES. Atrial premature complexes are characterized by premature P waves on ECG which are different in configuration from the P waves generated by the normal pacemaker complex in the SINOATRIAL NODE.Body Surface Potential Mapping: Recording of regional electrophysiological information by analysis of surface potentials to give a complete picture of the effects of the currents from the heart on the body surface. It has been applied to the diagnosis of old inferior myocardial infarction, localization of the bypass pathway in Wolff-Parkinson-White syndrome, recognition of ventricular hypertrophy, estimation of the size of a myocardial infarct, and the effects of different interventions designed to reduce infarct size. The limiting factor at present is the complexity of the recording and analysis, which requires 100 or more electrodes, sophisticated instrumentation, and dedicated personnel. (Braunwald, Heart Disease, 4th ed)Propafenone: An antiarrhythmia agent that is particularly effective in ventricular arrhythmias. It also has weak beta-blocking activity.Myocardial Reperfusion Injury: Damage to the MYOCARDIUM resulting from MYOCARDIAL REPERFUSION (restoration of blood flow to ischemic areas of the HEART.) Reperfusion takes place when there is spontaneous thrombolysis, THROMBOLYTIC THERAPY, collateral flow from other coronary vascular beds, or reversal of vasospasm.Heart Block: Impaired conduction of cardiac impulse that can occur anywhere along the conduction pathway, such as between the SINOATRIAL NODE and the right atrium (SA block) or between atria and ventricles (AV block). Heart blocks can be classified by the duration, frequency, or completeness of conduction block. Reversibility depends on the degree of structural or functional defects.Ether-A-Go-Go Potassium Channels: A family of voltage-gated potassium channels that are characterized by long N-terminal and C-terminal intracellular tails. They are named from the Drosophila protein whose mutation causes abnormal leg shaking under ether anesthesia. Their activation kinetics are dependent on extracellular MAGNESIUM and PROTON concentration.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Encainide: One of the ANTI-ARRHYTHMIA AGENTS, it blocks VOLTAGE-GATED SODIUM CHANNELS and slows conduction within the His-Purkinje system and MYOCARDIUM.Electrophysiology: The study of the generation and behavior of electrical charges in living organisms particularly the nervous system and the effects of electricity on living organisms.Follow-Up Studies: Studies in which individuals or populations are followed to assess the outcome of exposures, procedures, or effects of a characteristic, e.g., occurrence of disease.Voltage-Sensitive Dye Imaging: Optical imaging techniques used for recording patterns of electrical activity in tissues by monitoring transmembrane potentials via FLUORESCENCE imaging with voltage-sensitive fluorescent dyes.Telemetry: Transmission of the readings of instruments to a remote location by means of wires, radio waves, or other means. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Syncope: A transient loss of consciousness and postural tone caused by diminished blood flow to the brain (i.e., BRAIN ISCHEMIA). Presyncope refers to the sensation of lightheadedness and loss of strength that precedes a syncopal event or accompanies an incomplete syncope. (From Adams et al., Principles of Neurology, 6th ed, pp367-9)Treatment Outcome: Evaluation undertaken to assess the results or consequences of management and procedures used in combating disease in order to determine the efficacy, effectiveness, safety, and practicability of these interventions in individual cases or series.Pericardium: A conical fibro-serous sac surrounding the HEART and the roots of the great vessels (AORTA; VENAE CAVAE; PULMONARY ARTERY). Pericardium consists of two sacs: the outer fibrous pericardium and the inner serous pericardium. The latter consists of an outer parietal layer facing the fibrous pericardium, and an inner visceral layer (epicardium) resting next to the heart, and a pericardial cavity between these two layers.Cardiac Electrophysiology: The study of the electrical activity and characteristics of the HEART; MYOCARDIUM; and CARDIOMYOCYTES.Tachycardia, Ectopic Atrial: Abnormally rapid heartbeats originating from one or more automatic foci (nonsinus pacemakers) in the HEART ATRIUM but away from the SINOATRIAL NODE. Unlike the reentry mechanism, automatic tachycardia speeds up and slows down gradually. The episode is characterized by a HEART RATE between 135 to less than 200 beats per minute and lasting 30 seconds or longer.Cardiomyopathies: A group of diseases in which the dominant feature is the involvement of the CARDIAC MUSCLE itself. Cardiomyopathies are classified according to their predominant pathophysiological features (DILATED CARDIOMYOPATHY; HYPERTROPHIC CARDIOMYOPATHY; RESTRICTIVE CARDIOMYOPATHY) or their etiological/pathological factors (CARDIOMYOPATHY, ALCOHOLIC; ENDOCARDIAL FIBROELASTOSIS).Tetralogy of Fallot: A combination of congenital heart defects consisting of four key features including VENTRICULAR SEPTAL DEFECTS; PULMONARY STENOSIS; RIGHT VENTRICULAR HYPERTROPHY; and a dextro-positioned AORTA. In this condition, blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into the body often causing CYANOSIS.Sodium Channels: Ion channels that specifically allow the passage of SODIUM ions. A variety of specific sodium channel subtypes are involved in serving specialized functions such as neuronal signaling, CARDIAC MUSCLE contraction, and KIDNEY function.Procainamide: A class Ia antiarrhythmic drug that is structurally-related to PROCAINE.Pacemaker, Artificial: A device designed to stimulate, by electric impulses, contraction of the heart muscles. It may be temporary (external) or permanent (internal or internal-external).Connexin 43: A 43-kDa peptide which is a member of the connexin family of gap junction proteins. Connexin 43 is a product of a gene in the alpha class of connexin genes (the alpha-1 gene). It was first isolated from mammalian heart, but is widespread in the body including the brain.Mexiletine: Antiarrhythmic agent pharmacologically similar to LIDOCAINE. It may have some anticonvulsant properties.Quinidine: An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular ACTION POTENTIALS, and decreases automaticity. Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.Risk Factors: An aspect of personal behavior or lifestyle, environmental exposure, or inborn or inherited characteristic, which, on the basis of epidemiologic evidence, is known to be associated with a health-related condition considered important to prevent.Sotalol: An adrenergic beta-antagonist that is used in the treatment of life-threatening arrhythmias.Disopyramide: A class I anti-arrhythmic agent (one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent) with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties.Atrioventricular Block: Impaired impulse conduction from HEART ATRIA to HEART VENTRICLES. AV block can mean delayed or completely blocked impulse conduction.Tachycardia, Sinus: Simple rapid heartbeats caused by rapid discharge of impulses from the SINOATRIAL NODE, usually between 100 and 180 beats/min in adults. It is characterized by a gradual onset and termination. Sinus tachycardia is common in infants, young children, and adults during strenuous physical activities.Disease Models, Animal: Naturally occurring or experimentally induced animal diseases with pathological processes sufficiently similar to those of human diseases. They are used as study models for human diseases.Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.Magnetic Resonance Spectroscopy: Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).Arrhythmogenic Right Ventricular Dysplasia: A congenital cardiomyopathy that is characterized by infiltration of adipose and fibrous tissue into the RIGHT VENTRICLE wall and loss of myocardial cells. Primary injuries usually are at the free wall of right ventricular and right atria resulting in ventricular and supraventricular arrhythmias.Autonomic Nervous System: The ENTERIC NERVOUS SYSTEM; PARASYMPATHETIC NERVOUS SYSTEM; and SYMPATHETIC NERVOUS SYSTEM taken together. Generally speaking, the autonomic nervous system regulates the internal environment during both peaceful activity and physical or emotional stress. Autonomic activity is controlled and integrated by the CENTRAL NERVOUS SYSTEM, especially the HYPOTHALAMUS and the SOLITARY NUCLEUS, which receive information relayed from VISCERAL AFFERENTS.Heart Failure: A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (VENTRICULAR DYSFUNCTION), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as MYOCARDIAL INFARCTION.Prospective Studies: Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group.Potassium Channels, Voltage-Gated: Potassium channel whose permeability to ions is extremely sensitive to the transmembrane potential difference. The opening of these channels is induced by the membrane depolarization of the ACTION POTENTIAL.Myocardial Contraction: Contractile activity of the MYOCARDIUM.Epinephrine: The active sympathomimetic hormone from the ADRENAL MEDULLA. It stimulates both the alpha- and beta- adrenergic systems, causes systemic VASOCONSTRICTION and gastrointestinal relaxation, stimulates the HEART, and dilates BRONCHI and cerebral vessels. It is used in ASTHMA and CARDIAC FAILURE and to delay absorption of local ANESTHETICS.Heart Diseases: Pathological conditions involving the HEART including its structural and functional abnormalities.Echocardiography: Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic.KCNQ1 Potassium Channel: A voltage-gated potassium channel that is expressed primarily in the HEART.Refractory Period, Electrophysiological: The period of time following the triggering of an ACTION POTENTIAL when the CELL MEMBRANE has changed to an unexcitable state and is gradually restored to the resting (excitable) state. During the absolute refractory period no other stimulus can trigger a response. This is followed by the relative refractory period during which the cell gradually becomes more excitable and the stronger impulse that is required to illicit a response gradually lessens to that required during the resting state.Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of PROCAINE but its duration of action is shorter than that of BUPIVACAINE or PRILOCAINE.Atrioventricular Node: A small nodular mass of specialized muscle fibers located in the interatrial septum near the opening of the coronary sinus. It gives rise to the atrioventricular bundle of the conduction system of the heart.Wolff-Parkinson-White Syndrome: A form of ventricular pre-excitation characterized by a short PR interval and a long QRS interval with a delta wave. In this syndrome, atrial impulses are abnormally conducted to the HEART VENTRICLES via an ACCESSORY CONDUCTING PATHWAY that is located between the wall of the right or left atria and the ventricles, also known as a BUNDLE OF KENT. The inherited form can be caused by mutation of PRKAG2 gene encoding a gamma-2 regulatory subunit of AMP-activated protein kinase.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Epicardial Mapping: Recording the locations and measurements of electrical activity in the EPICARDIUM by placing electrodes on the surface of the heart to analyze the patterns of activation and to locate arrhythmogenic sites.Retrospective Studies: Studies used to test etiologic hypotheses in which inferences about an exposure to putative causal factors are derived from data relating to characteristics of persons under study or to events or experiences in their past. The essential feature is that some of the persons under study have the disease or outcome of interest and their characteristics are compared with those of unaffected persons.Cardiomyopathy, Dilated: A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.Heart Arrest: Cessation of heart beat or MYOCARDIAL CONTRACTION. If it is treated within a few minutes, heart arrest can be reversed in most cases to normal cardiac rhythm and effective circulation.Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.Ventricular Function: The hemodynamic and electrophysiological action of the HEART VENTRICLES.Signal Processing, Computer-Assisted: Computer-assisted processing of electric, ultrasonic, or electronic signals to interpret function and activity.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Rabbits: The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.Moricizine: An antiarrhythmia agent used primarily for ventricular rhythm disturbances.Endocardium: The innermost layer of the heart, comprised of endothelial cells.Molecular Conformation: The characteristic three-dimensional shape of a molecule.Pulmonary Veins: The veins that return the oxygenated blood from the lungs to the left atrium of the heart.Acetanilides: Compounds based on N-phenylacetamide, that are similar in structure to 2-PHENYLACETAMIDES. They are precursors of many other compounds. They were formerly used as ANALGESICS and ANTIPYRETICS, but often caused lethal METHEMOGLOBINEMIA.Postoperative Complications: Pathologic processes that affect patients after a surgical procedure. They may or may not be related to the disease for which the surgery was done, and they may or may not be direct results of the surgery.Potassium Channels: Cell membrane glycoproteins that are selectively permeable to potassium ions. At least eight major groups of K channels exist and they are made up of dozens of different subunits.Purkinje Fibers: Modified cardiac muscle fibers composing the terminal portion of the heart conduction system.Digitalis: A genus of toxic herbaceous Eurasian plants of the Plantaginaceae which yield cardiotonic DIGITALIS GLYCOSIDES. The most useful species are Digitalis lanata and D. purpurea.Recurrence: The return of a sign, symptom, or disease after a remission.Ryanodine Receptor Calcium Release Channel: A tetrameric calcium release channel in the SARCOPLASMIC RETICULUM membrane of SMOOTH MUSCLE CELLS, acting oppositely to SARCOPLASMIC RETICULUM CALCIUM-TRANSPORTING ATPASES. It is important in skeletal and cardiac excitation-contraction coupling and studied by using RYANODINE. Abnormalities are implicated in CARDIAC ARRHYTHMIAS and MUSCULAR DISEASES.Sinoatrial Node: The small mass of modified cardiac muscle fibers located at the junction of the superior vena cava (VENA CAVA, SUPERIOR) and right atrium. Contraction impulses probably start in this node, spread over the atrium (HEART ATRIUM) and are then transmitted by the atrioventricular bundle (BUNDLE OF HIS) to the ventricle (HEART VENTRICLE).Blood Pressure: PRESSURE of the BLOOD on the ARTERIES and other BLOOD VESSELS.Tachycardia, Atrioventricular Nodal Reentry: Abnormally rapid heartbeats caused by reentry of atrial impulse into the dual (fast and slow) pathways of ATRIOVENTRICULAR NODE. The common type involves a blocked atrial impulse in the slow pathway which reenters the fast pathway in a retrograde direction and simultaneously conducts to the atria and the ventricles leading to rapid HEART RATE of 150-250 beats per minute.Hemodynamics: The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.Tachycardia, Paroxysmal: Abnormally rapid heartbeats with sudden onset and cessation.Vagus Nerve: The 10th cranial nerve. The vagus is a mixed nerve which contains somatic afferents (from skin in back of the ear and the external auditory meatus), visceral afferents (from the pharynx, larynx, thorax, and abdomen), parasympathetic efferents (to the thorax and abdomen), and efferents to striated muscle (of the larynx and pharynx).Predictive Value of Tests: In screening and diagnostic tests, the probability that a person with a positive test is a true positive (i.e., has the disease), is referred to as the predictive value of a positive test; whereas, the predictive value of a negative test is the probability that the person with a negative test does not have the disease. Predictive value is related to the sensitivity and specificity of the test.Ventricular Function, Left: The hemodynamic and electrophysiological action of the left HEART VENTRICLE. Its measurement is an important aspect of the clinical evaluation of patients with heart disease to determine the effects of the disease on cardiac performance.Rats, Wistar: A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.Hydrogen Bonding: A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.Atrial Function: The hemodynamic and electrophysiological action of the HEART ATRIA.Cardiotonic Agents: Agents that have a strengthening effect on the heart or that can increase cardiac output. They may be CARDIAC GLYCOSIDES; SYMPATHOMIMETICS; or other drugs. They are used after MYOCARDIAL INFARCT; CARDIAC SURGICAL PROCEDURES; in SHOCK; or in congestive heart failure (HEART FAILURE).Halothane: A nonflammable, halogenated, hydrocarbon anesthetic that provides relatively rapid induction with little or no excitement. Analgesia may not be adequate. NITROUS OXIDE is often given concomitantly. Because halothane may not produce sufficient muscle relaxation, supplemental neuromuscular blocking agents may be required. (From AMA Drug Evaluations Annual, 1994, p178)Stroke Volume: The amount of BLOOD pumped out of the HEART per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume.Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures.Heart Defects, Congenital: Developmental abnormalities involving structures of the heart. These defects are present at birth but may be discovered later in life.GuanineBundle of His: Small band of specialized CARDIAC MUSCLE fibers that originates in the ATRIOVENTRICULAR NODE and extends into the membranous part of the interventricular septum. The bundle of His, consisting of the left and the right bundle branches, conducts the electrical impulses to the HEART VENTRICLES in generation of MYOCARDIAL CONTRACTION.Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.Cardiac Surgical Procedures: Surgery performed on the heart.Stellate Ganglion: A paravertebral sympathetic ganglion formed by the fusion of the inferior cervical and first thoracic ganglia.Andersen Syndrome: A form of inherited long QT syndrome (or LQT7) that is characterized by a triad of potassium-sensitive periodic paralysis, VENTRICULAR ECTOPIC BEATS, and abnormal features such as short stature, low-set ears, and SCOLIOSIS. It results from mutations of KCNJ2 gene which encodes a channel protein (INWARD RECTIFIER POTASSIUM CHANNELS) that regulates resting membrane potential.Coronary Disease: An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels.Sick Sinus Syndrome: A condition caused by dysfunctions related to the SINOATRIAL NODE including impulse generation (CARDIAC SINUS ARREST) and impulse conduction (SINOATRIAL EXIT BLOCK). It is characterized by persistent BRADYCARDIA, chronic ATRIAL FIBRILLATION, and failure to resume sinus rhythm following CARDIOVERSION. This syndrome can be congenital or acquired, particularly after surgical correction for heart defects.Hypokalemia: Abnormally low potassium concentration in the blood. It may result from potassium loss by renal secretion or by the gastrointestinal route, as by vomiting or diarrhea. It may be manifested clinically by neuromuscular disorders ranging from weakness to paralysis, by electrocardiographic abnormalities (depression of the T wave and elevation of the U wave), by renal disease, and by gastrointestinal disorders. (Dorland, 27th ed)Heterocyclic Compounds, Bridged-Ring: A class of organic compounds which contain two rings that share a pair of bridgehead carbon atoms.Electrophysiological Phenomena: The electrical properties, characteristics of living organisms, and the processes of organisms or their parts that are involved in generating and responding to electrical charges.Plant Extracts: Concentrated pharmaceutical preparations of plants obtained by removing active constituents with a suitable solvent, which is evaporated away, and adjusting the residue to a prescribed standard.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Bundle-Branch Block: A form of heart block in which the electrical stimulation of HEART VENTRICLES is interrupted at either one of the branches of BUNDLE OF HIS thus preventing the simultaneous depolarization of the two ventricles.Perfusion: Treatment process involving the injection of fluid into an organ or tissue.Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes, sparks, or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins.Base Pairing: Pairing of purine and pyrimidine bases by HYDROGEN BONDING in double-stranded DNA or RNA.Pachyrhizus: A plant genus of the family FABACEAE. Some Pachyrhizus have been reclassified to PUERARIA. Do not confuse with yam (IPOMOEA; or DIOSCOREA) or African yam bean (SPHENOSTYLIS).Myocardial Reperfusion: Generally, restoration of blood supply to heart tissue which is ischemic due to decrease in normal blood supply. The decrease may result from any source including atherosclerotic obstruction, narrowing of the artery, or surgical clamping. Reperfusion can be induced to treat ischemia. Methods include chemical dissolution of an occluding thrombus, administration of vasodilator drugs, angioplasty, catheterization, and artery bypass graft surgery. However, it is thought that reperfusion can itself further damage the ischemic tissue, causing MYOCARDIAL REPERFUSION INJURY.Exercise Test: Controlled physical activity which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used.Ventricular Dysfunction, Left: A condition in which the LEFT VENTRICLE of the heart was functionally impaired. This condition usually leads to HEART FAILURE; MYOCARDIAL INFARCTION; and other cardiovascular complications. Diagnosis is made by measuring the diminished ejection fraction and a depressed level of motility of the left ventricular wall.Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of CONNEXINS, the family of proteins which form the junctions.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Deoxyguanosine: A nucleoside consisting of the base guanine and the sugar deoxyribose.Isoproterenol: Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.Cardiomyopathy, Hypertrophic: A form of CARDIAC MUSCLE disease, characterized by left and/or right ventricular hypertrophy (HYPERTROPHY, LEFT VENTRICULAR; HYPERTROPHY, RIGHT VENTRICULAR), frequent asymmetrical involvement of the HEART SEPTUM, and normal or reduced left ventricular volume. Risk factors include HYPERTENSION; AORTIC STENOSIS; and gene MUTATION; (FAMILIAL HYPERTROPHIC CARDIOMYOPATHY).Risk Assessment: The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. (Last, Dictionary of Epidemiology, 1988)Potassium: An element in the alkali group of metals with an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the WATER-ELECTROLYTE BALANCE.Patch-Clamp Techniques: An electrophysiologic technique for studying cells, cell membranes, and occasionally isolated organelles. All patch-clamp methods rely on a very high-resistance seal between a micropipette and a membrane; the seal is usually attained by gentle suction. The four most common variants include on-cell patch, inside-out patch, outside-out patch, and whole-cell clamp. Patch-clamp methods are commonly used to voltage clamp, that is control the voltage across the membrane and measure current flow, but current-clamp methods, in which the current is controlled and the voltage is measured, are also used.Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Incidence: The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from PREVALENCE, which refers to all cases, new or old, in the population at a given time.Coronary Vessels: The veins and arteries of the HEART.Sarcoplasmic Reticulum: A network of tubules and sacs in the cytoplasm of SKELETAL MUSCLE FIBERS that assist with muscle contraction and relaxation by releasing and storing calcium ions.Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent.Ajmaline: An alkaloid found in the root of RAUWOLFIA SERPENTINA, among other plant sources. It is a class Ia antiarrhythmic agent that apparently acts by changing the shape and threshold of cardiac action potentials.Guinea Pigs: A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research.Potassium Channel Blockers: A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS.Sodium-Calcium Exchanger: An electrogenic ion exchange protein that maintains a steady level of calcium by removing an amount of calcium equal to that which enters the cells. It is widely distributed in most excitable membranes, including the brain and heart.Calsequestrin: Acidic protein found in SARCOPLASMIC RETICULUM that binds calcium to the extent of 700-900 nmoles/mg. It plays the role of sequestering calcium transported to the interior of the intracellular vesicle.Isolated Noncompaction of the Ventricular Myocardium: Rare congenital cardiomyopathies characterized by the lack of left ventricular myocardium compaction. The noncompaction results in numerous prominent trabeculations and a loose myocardial meshwork (spongy myocardium) in the LEFT VENTRICLE. Heterogeneous clinical features include diminished systolic function sometimes associated with left ventricular dilation, that presents either neonatally or progressively. Often, the RIGHT VENTRICLE is also affected. CONGESTIVE HEART FAILURE; PULMONARY EMBOLISM; and ventricular ARRHYTHMIA are commonly seen.Monitoring, Physiologic: The continuous measurement of physiological processes, blood pressure, heart rate, renal output, reflexes, respiration, etc., in a patient or experimental animal; includes pharmacologic monitoring, the measurement of administered drugs or their metabolites in the blood, tissues, or urine.DNA: A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).Catecholamines: A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine.Astemizole: Antihistamine drug now withdrawn from the market in many countries because of rare but potentially fatal side effects.Butylscopolammonium Bromide: Antimuscarinic quaternary ammonium derivative of scopolamine used to treat cramps in gastrointestinal, urinary, uterine, and biliary tracts, and to facilitate radiologic visualization of the gastrointestinal tract.Heterocyclic Compounds with 4 or More Rings: A class of organic compounds containing four or more ring structures, one of which is made up of more than one kind of atom, usually carbon plus another atom. The heterocycle may be either aromatic or nonaromatic.Tachycardia, Ectopic Junctional: A rare form of supraventricular tachycardia caused by automatic, not reentrant, conduction initiated from sites at the atrioventricular junction, but not the ATRIOVENTRICULAR NODE. It usually occurs during myocardial infarction, after heart surgery, or in digitalis intoxication with a HEART RATE ranging from 140 to 250 beats per minute.Aprindine: A class Ib anti-arrhythmia agent used to manage ventricular and supraventricular arrhythmias.Deoxycytosine Nucleotides: Cytosine nucleotides which contain deoxyribose as the sugar moiety.Prognosis: A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.Propanolamines: AMINO ALCOHOLS containing the propanolamine (NH2CH2CHOHCH2) group and its derivatives.Ventricular Dysfunction, Right: A condition in which the RIGHT VENTRICLE of the heart was functionally impaired. This condition usually leads to HEART FAILURE or MYOCARDIAL INFARCTION, and other cardiovascular complications. Diagnosis is made by measuring the diminished ejection fraction and a depressed level of motility of the right ventricular wall.Guanosine: A purine nucleoside that has guanine linked by its N9 nitrogen to the C1 carbon of ribose. It is a component of ribonucleic acid and its nucleotides play important roles in metabolism. (From Dorland, 28th ed)Sodium Channel Blockers: A class of drugs that act by inhibition of sodium influx through cell membranes. Blockade of sodium channels slows the rate and amplitude of initial rapid depolarization, reduces cell excitability, and reduces conduction velocity.KCNQ Potassium Channels: A family of delayed rectifier voltage-gated potassium channels that share homology with their founding member, KCNQ1 PROTEIN. KCNQ potassium channels have been implicated in a variety of diseases including LONG QT SYNDROME; DEAFNESS; and EPILEPSY.Pre-Excitation Syndromes: A group of conditions in which HEART VENTRICLE activation by the atrial impulse is faster than the normal impulse conduction from the SINOATRIAL NODE. In these pre-excitation syndromes, atrial impulses often bypass the ATRIOVENTRICULAR NODE delay and travel via ACCESSORY CONDUCTING PATHWAYS connecting the atrium directly to the BUNDLE OF HIS.Calcium Channels, L-Type: Long-lasting voltage-gated CALCIUM CHANNELS found in both excitable and nonexcitable tissue. They are responsible for normal myocardial and vascular smooth muscle contractility. Five subunits (alpha-1, alpha-2, beta, gamma, and delta) make up the L-type channel. The alpha-1 subunit is the binding site for calcium-based antagonists. Dihydropyridine-based calcium antagonists are used as markers for these binding sites.Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system.Chlorofluorocarbons, Methane: A group of methane-based halogenated hydrocarbons containing one or more fluorine and chlorine atoms.Magnesium Sulfate: A small colorless crystal used as an anticonvulsant, a cathartic, and an electrolyte replenisher in the treatment of pre-eclampsia and eclampsia. It causes direct inhibition of action potentials in myometrial muscle cells. Excitation and contraction are uncoupled, which decreases the frequency and force of contractions. (From AMA Drug Evaluations Annual, 1992, p1083)Plants, Medicinal: Plants whose roots, leaves, seeds, bark, or other constituent parts possess therapeutic, tonic, purgative, curative or other pharmacologic attributes, when administered to man or animals.Molecular Sequence Data: Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.Cisapride: A substituted benzamide used for its prokinetic properties. It is used in the management of gastroesophageal reflux disease, functional dyspepsia, and other disorders associated with impaired gastrointestinal motility. (Martindale The Extra Pharmacopoeia, 31st ed)Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Disease Susceptibility: A constitution or condition of the body which makes the tissues react in special ways to certain extrinsic stimuli and thus tends to make the individual more than usually susceptible to certain diseases.Phenethylamines: A group of compounds that are derivatives of beta- aminoethylbenzene which is structurally and pharmacologically related to amphetamine. (From Merck Index, 11th ed)Digoxin: A cardiotonic glycoside obtained mainly from Digitalis lanata; it consists of three sugars and the aglycone DIGOXIGENIN. Digoxin has positive inotropic and negative chronotropic activity. It is used to control ventricular rate in ATRIAL FIBRILLATION and in the management of congestive heart failure with atrial fibrillation. Its use in congestive heart failure and sinus rhythm is less certain. The margin between toxic and therapeutic doses is small. (From Martindale, The Extra Pharmacopoeia, 30th ed, p666)Terfenadine: A selective histamine H1-receptor antagonist devoid of central nervous system depressant activity. The drug was used for ALLERGY but withdrawn due to causing LONG QT SYNDROME.Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.G-Quadruplexes: Higher-order DNA and RNA structures formed from guanine-rich sequences. They are formed around a core of at least 2 stacked tetrads of hydrogen-bonded GUANINE bases. They can be formed from one two or four separate strands of DNA (or RNA) and can display a wide variety of topologies, which are a consequence of various combinations of strand direction, length, and sequence. (From Nucleic Acids Res. 2006;34(19):5402-15)Ouabain: A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE.Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).Electric Stimulation: Use of electric potential or currents to elicit biological responses.Excitation Contraction Coupling: A process fundamental to muscle physiology whereby an electrical stimulus or action potential triggers a myocyte to depolarize and contract. This mechanical muscle contraction response is regulated by entry of calcium ions into the cell.

The cyclo-oxygenase-dependent regulation of rabbit vein contraction: evidence for a prostaglandin E2-mediated relaxation. (1/3137)

1. Arachidonic acid (0.01-1 microM) induced relaxation of precontracted rings of rabbit saphenous vein, which was counteracted by contraction at concentrations higher than 1 microM. Concentrations higher than 1 microM were required to induce dose-dependent contraction of vena cava and thoracic aorta from the same animals. 2. Pretreatment with a TP receptor antagonist (GR32191B or SQ29548, 3 microM) potentiated the relaxant effect in the saphenous vein, revealed a vasorelaxant component in the vena cava response and did not affect the response of the aorta. 3. Removal of the endothelium from the venous rings, caused a 10 fold rightward shift in the concentration-relaxation curves to arachidonic acid. Whether or not the endothelium was present, the arachidonic acid-induced relaxations were prevented by indomethacin (10 microM) pretreatment. 4. In the saphenous vein, PGE2 was respectively a 50 and 100 fold more potent relaxant prostaglandin than PGI2 and PGD2. Pretreatment with the EP4 receptor antagonist, AH23848B, shifted the concentration-relaxation curves of this tissue to arachidonic acid in a dose-dependent manner. 5. In the presence of 1 microM arachidonic acid, venous rings produced 8-10 fold more PGE2 than did aorta whereas 6keto-PGF1alpha and TXB2 productions remained comparable. 6. Intact rings of saphenous vein relaxed in response to A23187. Pretreatment with L-NAME (100 microM) or indomethacin (10 microM) reduced this response by 50% whereas concomitant pretreatment totally suppressed it. After endothelium removal, the remaining relaxing response to A23187 was prevented by indomethacin but not affected by L-NAME. 7. We conclude that stimulation of the cyclo-oxygenase pathway by arachidonic acid induced endothelium-dependent, PGE2/EP4 mediated relaxation of the rabbit saphenous vein. This process might participate in the A23187-induced relaxation of the saphenous vein and account for a relaxing component in the response of the vena cava to arachidonic acid. It was not observed in thoracic aorta because of the lack of a vasodilatory receptor and/or the poorer ability of this tissue than veins to produce PGE2.  (+info)

Preconditioning in immature rabbit hearts: role of KATP channels. (2/3137)

BACKGROUND: The protective effects of ischemic preconditioning have been shown to occur in adult hearts of all species studied. We determined whether immature hearts normoxic or chronically hypoxic from birth could be preconditioned, the time window or memory of the cardioprotective effect, and the involvement of the KATP channel. METHODS AND RESULTS: Isolated immature rabbit hearts (7 to 10 days old) were subjected to 0, 1, or 3 cycles of preconditioning consisting of 5 minutes of global ischemia plus 10 minutes of reperfusion. This was followed by 30 minutes of global ischemia and 35 minutes of reperfusion. Normoxic hearts (FIO2=0.21) subjected to 1 cycle of preconditioning recovered 70+/-7% of left ventricular developed pressure compared with 43+/-8% recovery in nonpreconditioned controls. Three cycles of preconditioning did not result in additional recovery (63+/-8%). Hearts from rabbits raised from birth in hypoxic conditions (FIO2=0.12) and subjected to 1 and 3 preconditioning cycles did not show increased recovery (68+/-8% and 65+/-5%) compared with nonpreconditioned hypoxic controls (63+/-9%), although the recovery was greater in chronically hypoxic hearts than in age-matched normoxic controls. Increasing the recovery period after the preconditioning stimulus from 10 to 30 minutes resulted in a loss of cardioprotection. Pretreatment of normoxic hearts for 30 minutes with the KATP channel blocker 5-hydroxydecanoate (300 micromol/L) completely abolished preconditioning (70+/-7% to 35+/-9%) but had no effect on nonpreconditioned hearts (40+/-8%). CONCLUSIONS: Immature hearts normoxic from birth can be preconditioned, whereas immature hearts hypoxic from birth cannot. Preconditioning in normoxic immature hearts is associated with activation of the KATP channel.  (+info)

Modulation of AV nodal and Hisian conduction by changes in extracellular space. (3/3137)

Previous studies have demonstrated that the extracellular space (ECS) component of the atrioventricular (AV) node and His bundle region is larger than the ECS in adjacent contractile myocardium. The potential physiological significance of this observation was examined in a canine blood-perfused AV nodal preparation. Mannitol, an ECS osmotic expander, was infused directly into either the AV node or His bundle region. This resulted in a significant dose-dependent increase in the AV nodal or His-ventricular conduction time and in the AV nodal effective refractory period. Mannitol infusion eventually resulted in Wenckebach block (n = 6), which reversed with mannitol washout. The ratio of AV nodal to left ventricular ECS in tissue frozen immediately on the development of heart block (n = 8) was significantly higher in the region of block (4.53 +/- 0.61) compared with that in control preparations (2.23 +/- 0.35, n = 6, P < 0.01) and donor dog hearts (2.45 +/- 0.18, n = 11, P < 0.01) not exposed to mannitol. With lower mannitol rates (10% of total blood flow), AV nodal conduction times increased by 5-10% and the AV node became supersensitive to adenosine, acetylcholine, and carbachol, but not to norepinephrine. We conclude that mannitol-induced changes in AV node and His bundle ECS markedly alter conduction system electrophysiology and the sensitivity of conductive tissues to purinergic and cholinergic agonists.  (+info)

Delayed rectifier potassium current in undiseased human ventricular myocytes. (4/3137)

OBJECTIVE: The purpose of the study was to investigate the properties of the delayed rectifier potassium current (IK) in myocytes isolated from undiseased human left ventricles. METHODS: The whole-cell configuration of the patch-clamp technique was applied in 28 left ventricular myocytes from 13 hearts at 35 degrees C. RESULTS: An E-4031 sensitive tail current identified the rapid component of IK (IKr) in the myocytes, but there was no evidence for an E-4031 insensitive slow component of IK (IKs). When nifedipine (5 microM) was used to block the inward calcium current (ICa), IKr activation was fast (tau = 31.0 +/- 7.4 ms, at +30 mV, n = 5) and deactivation kinetics were biexponential and relatively slow (tau 1 = 600.0 +/- 53.9 ms and tau 2 = 6792.2 +/- 875.7 ms, at -40 mV, n = 7). Application of CdCl2 (250 microM) to block ICa altered the voltage dependence of the IKr considerably, slowing its activation (tau = 657.1 +/- 109.1 ms, at +30 mV, n = 5) and accelerating its deactivation (tau = 104.0 +/- 18.5 ms, at -40 mV, n = 8). CONCLUSIONS: In undiseased human ventricle at 35 degrees C IKr exists having fast activation and slow deactivation kinetics; however, there was no evidence found for an expressed IKs. IKr probably plays an important role in the frequency dependent modulation of repolarization in undiseased human ventricle, and is a target for many Class III antiarrhythmic drugs.  (+info)

Electrophysiologic effect of enalapril on guinea pig papillary muscles in vitro. (5/3137)

AIM: To study the direct effect of enalapril on cellular electrophysiology of myocardium. METHODS: Conventional microelectrodes technique was used to record the action potentials (AP) of guinea pig papillary muscles. RESULTS: Enalapril caused an increase of the AP amplitude (APA) and the resting potential (RP) in a concentration-dependent manner without any significant change of AP duration, Vmax and overshoot of AP. Superfusion of ouabain 0.5 mumol.L-1 reduced APA and RP, induced stable delayed after-depolarizations (DAD) at different basic cycle lengths (BCL) in a frequency-dependent manner. At BCL 200 ms, the amplitude of DAD was large enough to induce nonsustained triggered activity (TA). In additional presence of enalapril 10 mumol.L-1, the DAD amplitude at 500, 400, 300, and 200 ms were decreased from 5.3 +/- 2.3, 5.9 +/- 2.8, 7.4 +/- 2.1, and 8.9 +/- 1.3 to 2.6 +/- 0.7, 3.1 +/- 1.0, 3.7 +/- 1.5, and 5.3 +/- 1.1 (mV) respectively, all P < 0.01. The compensation intervals were increased in a similar frequency-dependent manner. The number of TA induced at BCL 200 ms was decreased from 3.6 +/- 0.7 to 0.8 +/- 0.2 (P < 0.05). CONCLUSION: Enalapril directly inhibits DAD and TA induced by ouabain through increasing RP and APA, which may contribute to its anti-arrhythmic effect.  (+info)

Effects of dauricine, quinidine, and sotalol on action potential duration of papillary muscles in vitro. (6/3137)

AIM: To compare the characteristics of dauricine, sotalol, and quinidine on action potential duration (APD). METHODS: Using intracellular microelectrode method to record APD in guinea pig papillary muscles. RESULTS: Dauricine 20 mumol.L-1 prolonged action potential at 90% repolarization, the percent of APD prolongation were 22 +/- 8, 11 +/- 6, 9 +/- 5, 7 +/- 5, 6 +/- 3, 4.3 +/- 2.8, 4.5 +/- 2.8 at the cycle lengths of 200-2000 ms, dauricine became more effective in lengthening APD at short cycle lengths. The effect of dauricine on prolonging APD exhibited normal use-dependence, whereas quinidine 1 mumol.L-1 and sotalol 10 mumol.L-1 were less effective in lengthening APD at short cycle lengths. The effect of quinidine and sotalol on APD exhibited reverse use-dependence. CONCLUSSION: The effect of dauricine on APD depends on activation frequency.  (+info)

Imipramine blocks the transient outward potassium current in rat ventricular myocytes. (7/3137)

AIM: To examine the effects of imipramine on transient outward potassium current (I(to) in rat ventricular myocytes. METHODS: The patch-clamp whole-cell recording techniques were used. RESULTS: Imipramine resulted in a concentration-dependent inhibition of I(to) with the IC50 of 6.0 mumol.L-1 and a concentration-dependent acceleration of I(to) inactivation. The blocking showed no difference at different testing membrane potentials. Imipramine produced slight effects (about 3 and 4 mV, respectively) on steady-state activation and inactivation curves of I(to), and tended to prolong the recovery of I(to) from inactivation (tau control = 37 +/- 11 ms; tau drug = 58 +/- 17 ms), but not significant (n = 4, P > 0.05). The inhibitory effect of imipramine on Ito was increased when the prepulses were prolonged progressively from 0 to 120 ms. (tau control = 22 +/- 8 ms; tau drug = 14 +/- 5 ms). CONCLUSIONS: Imipramine blocked Ito in concentration-dependent but voltage-independent manners, and with "open channel blocking" properties.  (+info)

Effects of cycloprotobuxine-A on atrial fibrillation. (8/3137)

AIM: To study the effects of cycloprotobuxine-A (Cyc-A) on atrial fibrillation. METHODS: Atrial fibrillations in vivo and in vitro were induced by arrhythmogenic drugs. Action potentials were measured by the standard microelectrode technique. RESULTS: Cyc-A, similar to or slightly stronger than amiodarone (Ami), decreased incidences of atrial fibrillation elicited by CaCl2-acetylcholine in mice and increased doses of aconitine, ouabain, or adrenaline to elicit atrial fibrillation in isolated guinea pig atria. Cyc-A 0.3-100 mumol.L-1 decreased the normal automaticity and 0.3-30 mumol.L-1 attenuated or almost abolished the isoprenaline-induced abnormal increase in automaticity in sinus nodal cells. In isolated left atria, Cyc-A 0.3-30 mumol.L-1 inhibited the abnormal rhythmic activity elicited by adrenaline, prolonged action potential duration (APD) and effective refractory period, and reduced excitability. At 3-30 mumol.L-1, Cyc-A also decreased the maximal velocity of depolarization (Vmax). Cyc-A antagonized the acetylcholine-induced shortening of APD. These electrophysiologic effects were similar to those of amiodarone, but Ami did not affect the Vmax. CONCLUSION: Cyc-A produces a protective effect against experimental atrial fibrillation via a prolongation of repolarization, a decease of automaticity, and an inhibition of excitability.  (+info)

  • A non-selective beta-adrenergic antagonist … A non-selective beta-adrenergic antagonist with a long half-life, used in cardiovascular disease to treat arrhythmias, angina pectoris, and hypertension. (
  • While defibrillators are very effective at preventing death from ventricular arrhythmias, shocks for arrhythmia are painful and decrease quality of life, 3, 4 leading to trials of both pharmacological and ablative techniques to decrease shocks in this population. (
  • Acute myocardial ischemia leads to electrophysiological inhomogeneities in APD, conduction velocity, and refractoriness, which provide the substrate for reentry initiation and maintenance and may lead to malignant arrhythmias. (
  • MILPITAS, Calif. , May 26, 2016 /PRNewswire/ -- Armetheon, Inc., a specialty pharmaceutical company developing novel small molecule drugs for cardiovascular diseases, today announced that it has completed the acquisition of budiodarone, an anti-arrhythmic agent in Phase 2 development. (