Cause Of Arrhythmias Research Articles

Perspectives on the current treatment of cardiac arrhythmias

Our current understanding of human cardiac arrhythmias is primitive and their treatment is largely empirical. For a few arrhythmias for which the mechanism is known, this information is valuable in selecting therapy. Primary methods for arrhythmia detection are 24-hour electrocardiographic recordings, patient-activated recordings, exercise and cardiac electrophysiologic studies. A search for removable causes of arrhythmia should be sought before instituting specific treatment with antiarrhythmic drugs, surgery or implantable devices. Over the past 20 years, the spectrum of antiarrhythmic drug action has broadened; sodium channel blockers, β-adrenergic blockers and calcium channel blockers have extended our therapeutic options, but the ideal drug has yet to appear. Efficacy and convenience of antiarrhythmic drugs have improved significantly, but adverse effects and drug interactions still occur much too frequently. The outlook for patients with malignant arrhythmias has improved significantly. However, the 2 methods for evaluating therapy of malignant arrhythmias are time-consuming, uncomfortable and expensive. Basic and clinical research is rapidly advancing our knowledge and effectiveness in dealing with cardiac arrhythmias. As a result, we can expect substantial improvements in arrhythmia control in the future.

Effects of pacing on triggered activity induced by early afterdepolarizations.

Early afterdepolarizations (EADs) are depolarizing potentials that occur during phase 2 or phase 3 of repolarization. They can induce triggered activity and have been proposed as a cause for arrhythmias in the heart in situ. To determine the response of EADs and triggered activity to interventions analogous to those used in the clinic for identifying arrhythmogenic mechanisms, we used a pacing protocol to study the response of EADs to sustained drive and extrastimuli. Cesium chloride (5 to 20 mM), which induces triggered arrhythmias in the intact dog, was used to induce EADs in isolated canine Purkinje fibers, and these were studied by microelectrode techniques. Cesium prolonged action potential duration and induced two types of EADs. At a potassium concentration of 4 mM, EADs occurred at membrane potentials of -3 to -30 mV. They were initiated 240 to 680 msec after the action potential upstroke and were 2 to 30 mV in amplitude. Their amplitude increased as drive cycle length increased, but their coupling interval to the action potential did not change with drive cycle length. These EADs did not induce triggered action potentials. At a potassium concentration of 2 mM, EADs usually occurred at higher membrane potentials (-50 to -70 mV) and longer coupling intervals (470 to 1360 msec) and were manifested as a delay of phase 3 repolarization. These EADs induced triggered action potentials. When the triggered rhythms became sustained, premature stimuli either reset or terminated them, depending on the maximum diastolic potential. Termination occurred more frequently as the maximum diastolic potential increased. The extent of overdrive suppression induced by pacing for 15 sec to 3 min also increased as the maximum diastolic potential increased. In summary, cesium induced EADs at low or high membrane potentials. The former did not induce triggered activity, but the latter did. The triggered rhythms that occurred were similar to abnormal automatic mechanisms in their response to overdrive pacing and extrastimuli.

Diuretic-induced magnesium losses.

Long term administration of common loop or distal tubular diuretics may cause somatic magnesium depletion. The resultant deficiency of Mg++ destabilises the myocardium electrically and is a principal cause of cardiac arrhythmias ascribed to diuretics. The adverse effects of diuretics caused by Mg++ depletion can be avoided by selecting diuretics that do not cause magnesium deficiency, minimising the diuretic dose, supplementation of Mg++ intake, or the concomitant use of a K+-retaining, Mg++-sparing diuretic.

Induction and termination of triggered activity by pacing in isolated canine Purkinje fibers.

The clinical importance of delayed afterdepolarizations and resultant triggered activity as a cause of cardiac arrhythmias is uncertain. We studied the response of ouabain-induced delayed afterdepolarizations and triggered activity to a pacing protocol similar to those used clinically in an effort to quantify the types of responses to pacing that occur as a result of this arrhythmogenic mechanism. Isolated canine Purkinje fibers were superfused with 2 X 10(7)M ouabain until delayed afterdepolarizations occurred and attained an amplitude of 5 mV at a paced cycle length of 500 msec. We then studied the induction of triggered activity in these fibers by pacing. We found that: (1) As the pacing cycle length decreased, the coupling interval from the last paced beat to the first triggered beat decreased and 83% of fibers developed triggered activity. (2) The coupling interval of the first triggered beat after single (S2) or double (S2S3) premature beats was in part dependent on preceding pacing cycle lengths. S2 pacing induced triggered activity in 39% of fibers, and S2S3 pacing induced triggered activity in 48% of fibers. We then studied the termination of ouabain-induced sustained rhythmic activity by pacing: 89% of sustained rhythmic activity could be terminated by overdrive pacing at a cycle length less than or equal to 300 msec. The coupling interval of the first beat or first delayed afterdepolarization after the termination of overdrive decreased as pacing cycle length decreased. S2 premature beats reset the sustained rhythmic activity and terminated 14% of sustained rhythmic activity. The coupling interval of the first escape beat or delayed afterdepolarization after S2S3 premature beats decreased as the S2S3 interval shortened, and S2S3 terminated 26% of sustained rhythmic activity. Pacing at an S1S1 cycle length of 400 msec followed by an S2 terminated 50% of sustained rhythmic activity; S1S1 at a cycle length of 400 msec followed by S2S3 terminated 85% of sustained rhythmic activity. This quantitative demonstration of the responses of delayed afterdepolarizations, triggered activity, and sustained rhythmic activity to pacing may be useful in differentiating these from other mechanisms for arrhythmias.

Amiodarone in refractory life-threatening ventricular arrhythmias.

Ninety-six patients with life-threatening ventricular arrhythmias refractory to two or more conventional agents were treated with amiodarone and followed for 6 to 40 months (mean, 15 months). Currently, 75 are alive and well. Seven patients died from nonarrhythmic and five from arrhythmic causes. Nonfatal arrhythmias recurred in four patients, one with early and three with late onset. Intolerable side effects occurred in five patients but heart failure was not aggravated by the drug. On 24-hour Holter recordings done before and serially during therapy in 72 patients, amiodarone eliminated episodes of ventricular tachycardia and complex ectopy and reduced total ectopic beat counts by 90% or more in all but 4 patients. In contrast, ventricular tachycardia inducible by programmed electrical stimulation was suppressed in only 50% of patients, but failure of such suppression did not compromise an excellent clinical outcome. Thus, amiodarone is highly effective in the prophylaxis of recurrent refractory life-threatening ventricular arrhythmias.

Value and limitations of clinical electrophysiologic study in assessment of patients with unexplained syncope

We assessed the value of clinical electrophysiologic study using intracardiac recording and programed electrical stimulation in 34 patients who had unexplained syncope and/or presyncope. All patients had normal electrocardiograms, and no abnormality was detected by clinical examination, ambulatory electrocardiographic recording, or treadmill testing. The electrophysiologic results were diagnostic in four patients (11.8 percent) and led to appropriate therapy that totally relieved symptoms. The results were abnormal but not diagnostic in two patients (5.8 percent) and normal in the remaining 28 patients (82.4 percent). The patients were followed for a mean period of 15 months (range two to 44) after electrophysiologic testing. Sixteen patients (47 percent) had no further episodes in the absence of any intervention. In four patients (11.8 percent), a definitive diagnosis was made during follow-up. In seven patients, permanent pacing was instituted empirically with relief of syncope. Two patients continued to have syncopal spells. We conclude that the diagnostic yield of electrophysiologic testing is low in a patient population that has no electrocardiographic abnormality or clinical evidence of cardiac disease. Empirical permanent pacing in patients with symptoms continuing after our study appeared to be beneficial, but this result is difficult to evaluate because of the high incidence of spontaneous remission in this group. Persistent attempts to document electrocardiographic abnormalities during a typical episode of symptoms appears to be the only definitive way to confirm or exclude an arrhythmic cause of the symptoms.

Sudden death in mitral valve prolapse: Associated accessory atrioventricular pathways

Sudden death in patients with mitral valve prolapse is a rare complication with a possible arrhythmic mechanism. We made a detailed postmortem examination of the conduction system in three patients with MVP who died suddenly. One patient who died in cardiac failure had a normal conduction system. The two other patients with no cardiac symptoms prior to death had both accessory atrioventricular pathways. These findings suggest a higher incidence than hitherto known of accessory bypass tracts in patients with MVP who die suddenly, and support the presumption of an arrhythmic cause of death.

Hypomagnesemia and Ventricular Tachycardia: A Complication of Ulcerative Colitis and Parenteral Hyperalimentation in a Nondigitalized Noncardiac Patient

A nondigitalized patient without heart disease, but with ulcerative colitis on parenteral hyperalimentation, developed ventricular tachycardia in association with hypomagnesemia. Magnesium infusions were successful in suppressing the arrhythmia, but because of ongoing fecal losses, hypomagnesemia and ventricular tachycardia recurred each time the infusion was stopped. After total colectomy, the patient remained normomagnesemic and free of arrhythmias. The few previous descriptions of arrhythmias attributed to hypomagnesemia in nondigitalized patients are reviewed. The importance of recognizing hypomagnesemia as an easily reversible cause of arrhythmias is stressed.

Concentrations of magnesium, calcium, potassium, and sodium in human heart muscle after acute myocardial infarction.

Atomic absorption spectrometry was used to measure magnesium, calcium, and sodium, and emission spectrometry to measure potassium, in myocardium (left and right ventricles) of 26 control subjects who died of acute trauma. Results were expressed in mumol/g of proteins. Mg/Ca and K/Na ratios were also determined. The same measurements were made in 24 patients who died from acute myocardial infarction. Samples were also taken from the necrotic area. Mg/Ca and K/Na ratios were significantly higher in the left ventricle of both populations, thus providing evidence of anatomical and physiological differences between the two ventricles. As a result of cytolysis and anoxia, the Mg/Ca ratio was very significantly inverted, and the K/Na ratio very significantly smaller, for samples from the necrotic area. In these clinical conditions arrhythmias could certainly be considered likely, and there is reason to believe that magnesium depletion may be a cause of arrhythmias.

Mechanisms of cardiac arrhythmias after the Mustard operation for transposition of the great arteries

To determine the mechanisms of the cardiac arrhythmias frequently seen after the Mustard operation for transposition of the great arteries, intracardiac electrophysiologic studies were performed in 52 children 1 to 8 years after the Mustard operation. Sinus nodal automaticity as judged from the response to rapid atrial pacing was abnormal in 28 of the 52 children. Sinoatrial conduction (conduction of the sinus impulse to the atrium) was found to be abnormal in three of nine patients studied with the atrial extrastimulus method. Conduction of the sinus impulse from the high right atrium to the atrioventricular (A-V) node was abnormally delayed in only 2 of 41 subjects. The low lateral wall of the right atrium was depolarlzed late in 3 of 11 subjects (including the preceding 2). Two subjects showed delayed A-V nodal conduction and one delayed His-Purkinje conduction. The mechanism of supraventricular tachycardia induced in the laboratory was determined to be sinoatrial nodal reentry in four subjects and atrial muscle reentry in four. Two of the four with atrial muscle reentry had prolonged high right atrium to low lateral right atrium intervals during sinus rhythm. Thus, damage to the sinus node remains the most common cause of arrhythmias after the Mustard operation. In addition, delayed atrial conduction may predispose to atrial muscle reentrant tachycardia.

Electrocution during anaesthesia

Cardiac arrest due to electrocution occurred in a young obstetric patient undergoing laparotomy. The patient subsequently died despite initial resuscitation. The cause was traced to an inappropriate and faulty switch in the base of the operating table; the circuit was completed by the ECG monitor which was of the direct earth type.

Reentrant excitation as a cause of cardiac arrhythmias.

Mechanisms that cause reentry were defined in rings of tissue cut from jellyfish as early as 1906 by Mayer. The concepts were developed by Mines and Garrey during the next 10 years. Lewis then tried to demonstrate that reentry caused atrial flutter. Lewis, Garrey, and later Moe also proposed that atrial fibrillation was caused by reentry. Rosenblueth provided additional experimental evidence that reentry could cause atrial arrhythmias after crushing the intercaval bridge of atrial muscle. Recent studies by Allessie using microelectrodes have provided detailed evidence for reentry in atrial tissue. Mines in 1913 also proposed that reentry could occur in the AV node. Scherf then introduced the concept of functional longitudinal dissociation as a cause of return extrasystoles and this was later shown to happen in the node by Moe and his colleagues. Reentry can also occur between atria and ventricles utilizing accessory connecting pathways. Schmitt and Erlanger in 1913 were the first to do experiments which indicated that reentry can also occur in the ventricles. Subsequently it was shown that reentry can occur in Purkinje fiber bundles. Reentry in ventricular muscle may also cause some of the arrhythmias that occur after myocardial infarction.

Atrioventricular Conduction Times and Atrioventricular Nodal Conductivity during Enflurane Anesthesia in Dogs

Because alterations in conduction may be important as a cause of arrhythmias during anesthesia, the authors used His-bundle electrocardiography to evaluate the effects of enflurane on atrioventricular (AV) nodal, His–Purkinje, and ventricular conduction times in dogs. Evaluations were made in hearts beating spontaneously and during atrial pacing at rates between 120 and 200 beats/min. To test the effects of enflurane on the atrial effective refractory period, functional refractory period of the AV node, and AV nodal conductivity, atrial extrastimuli (test beats) were delivered at various cycle lengths (500 msec or less) after the last of a series of paced beats at 120 or 200 beats/min. AV nodal conductivity was evaluated by measurements of minimum conduction time, fatigue (the relation of minimum conduction time to change in heart rate), and interval-related conductivity (the prolongation of AV nodal conduction time beyond minimum conduction time related to prematurity of test response). Increasing concentrations of enflurane from 1.0 to 2.0 MAC prolonged AV nodal, but not His–Purkinje or ventricular, conduction times. AV nodal conduction time increased as heart rate was increased, and this rate-dependency was enhanced by enflurane. His–Purkinje and ventricular conduction times were not affected by rate or enflurane. The atrial effective refractory period, functional refractory period of the AV node, and AV nodal conductivity were depressed by enflurane. For the His–Purkinje and ventricular conduction system, the present results are in contrast to those previously reported for halothane. Conduction changes are necessary for ventricular arrhythmias caused by re-entry of excitation. These findings may in part explain the clinical impression that ventricular arrhythmias appear less likely to occur with enflurane than with halothane.

Action potentials, afterpotentials, and arrhythmias.

Triggered activity must be added to spontaneous activity and to circus movement as a cause for extrasystoles and tachycardias of either atrial or ventricular origin. The activity of a triggerable focus requires phase 4 depolarization caused by an afterpotential; this distinguishes it from the activity seen in circus movement. A triggerable focus becomes rhythmically active only if driven at a critical rate or by a critically timed premature impulse; this distinguishes it from a focus of spontaneous or automatic activity. The ease of triggering a triggerable focus increases in the presence of catecholamines; triggerable foci in the atrium become quiescent when exposed to acetylcholine. At the present time, fibers within the coronary sinus provide the most persuasive example of triggered activity as a possible cause of arrhythmias of clinical significance. It is possible that the coupled extrasystoles of digitalis toxicity may be triggered; there is every reason to believe that further examples of triggered arrhythmias of possible clinical significance will be discovered.

Electrical malfunction at endoscopy. Possible cause of arrhythmia and death

Electrical malfunction at endoscopy. Possible cause of arrhythmia and death

Effects of Practolol on Respiratory and Cardiovascular Responses to Isoproterenol in Normal and Asthmatic Subjects

One of the most common causes of cardiac arrhythmia is COLD, chronic obstructive lung disease. Patients with asthma, chronic bronchitis or emphysema have episodes of hypoxia and are receiving catecholamines and theophylline. All of these factors contribute to cause cardiac arrhythmias.

Inappropriate ventilation and hypoxemia as causes of cardiac arrhythmias: The control of arrhythmias without antiarrhythmic drugs

Severe ventricular and supraventricular arrhythmias may be produced by inappropriate ventilation (hyperventilation or hypoventilation), hypoxemia or metabolic acidosis. Conventional therapy with antiarrhythmic drugs and precordial counter-shock is ineffective unless the underlying metabolic abnormalities are corrected. Nine representative patients are described and the physiologic determinants of hypoxemia and hyperventilation in the critically ill patient discussed.

Clinical pharmacology of general anesthetics.

The past decade has seen great interest in the clinical pharmacology of general anesthetics. Recently introduced drugs, such as halothane or methoxyflurane, have already been studied in more detail than ether or nitrous oxide had been during the first century of their clinical use. This review discusses some aspects of the actions of anesthetics of immediate clinical significance to the practicing anesthesiologist. Uptake and distribution of anesthetics in the body follows certain well‐defined laws and is a continuously changing process. Volatility and the blood to gas partition ratio are the main factors influencing the onset of inhalation anesthetics, while a high blood to tissue ratio will aid recovery. Lack of ionization and high lipoid solubility explain the rapid onset of the useful intravenous agents. With these drugs the clinical “depth” of anesthesia is often unrelated to the blood level, their action being markedly influenced by dosage and premedication. Most general anesthetics are direct myocardial depressants and cause a variable degree of peripheral vasodilation, but those which increase blood catecholamine levels cause less hypotension. Hypercarbia is a major cause of cardiac arrhythmias during anesthesia, particularly with cyclopropane and halothane. Contrary to some opinions, liver dysfunction is probably no more common after halothane than after other agents, although there may be a particular danger associated with its repeated administration. Many factors other than the general anesthetic itself increase the incidence of postoperative vomiting; opiate premedication is the main factor which is under the direct control of the anesthesiologist.

Management of cardiac arrhythmias during anaesthesia

Disorders of cardiac rhythm may be described as supraventricular or ventricular in origin. The former for the most part are innocuous. Ventricular premature systoles may be the forerunner of ventricular tachycardia or ventricular fibrillation. Ventricular tachycardia if persistent is accompanied by failing circulation. The majority of the arrhythmias observed during anaesthesia can be attributed to hypoxia or accumulation of carbon dioxide. In the opinion of certain anaesthetists, if these two causes of arrhythmia are avoided there is no need for an antiarrhythmia drug. Procaine amide has proven of value in the control of the ventricular arrhythmias which occur during cyclopropane anaesthesia. Rapidly acting digitalis preparations, particularly acetyl strophanthidin, may be needed to slow a rapidly beating heart (supraventricular tachycardias). The ventricular arrhythmias which accompany digitalis toxicity are caused by loss of intracellular potassium. Potassium chloride is effective in the control of digitalis-induced arrhythmias and should be considered in other instances as well.