Electrophysiological

Platiaum and its alloys are also used as biomedical electrodes, eg, platiaum—indium wires for permanent and temporary pacemaker leads and defibrillator leads. Electrophysiology catheters, which contain platinum electrodes and marker bands, have been used to map the electrical pathways of the heart so that appropriate treatment, such as a pacemaker, can be prescribed. 

Additionally, the electrophysiological effects are often obtained from normal myocardial preparations and the abnormalities of cellular electrophysiology which cause arrhythmias in a diseased myocardium may be uniquely related to the disease process (10). Nevertheless, antiarrhythmic agent classifications have been useful as a mnemonic device. 

The Class I agents decrease excitability, slow conduction velocity, inhibit diastoHc depolarization (decrease automaticity), and prolong the refractory period of cardiac tissues (1,2). These agents have anticholinergic effects that may contribute to the observed electrophysiologic effects. Heart rates may become faster by increasing phase 4 diastoHc depolarization in SA and AV nodal cells. This results from inhibition of the action of vagaHy released acetylcholine [S1-84-3] which, allows sympathetically released norepinephrine [51-41-2] (NE) to act on these stmctures (1,2). 

Glass lA Antiarrhythmic Agents. Class lA antiarrhythmic agents decrease automaticity, ie, depress pacemaker rates, especially ectopic foci rates produce moderate depression of phase 0 depolarization and thus slow conduction in atria, A-V node, His-Purkinje system, and ventricles prolong repolarization, ie, lengthen action potential duration increase refractoriness and depress excitabiHty. These electrophysiological effects are manifested in the ECG by increases in the PR, QRS, and QT intervals. 

The properties of -adrenoceptor blockers that contribute to antiarrhythmic effects are antagonism of neural/humoral P-adrenergic activity, and antagonism of catecholamine-mediated electrophysiological properties, ie, increase refractory period and decrease in the rate of diastoHc depolarization, ie, decrease automaticity and slow atrioventricular conduction (1,2). 

Elestolol sulfate is a nonselective, ultrashort acting P-adrenoceptor blocker. It has no ISA and produces weak inhibition of the fast sodium channel. The dmg is under clinical investigation for supraventricular tachyarrhythmias, unstable angina, and acute MI. In humans, flestolol has hemodynamics and electrophysiologic effects similar to those of other P-adrenoceptor blockers. The pharmacokinetics of flestolol are similar to those of esmolol. It is 50 times more potent than esmolol and the elimination half-life is 7.2 min. Recovery from P-adrenoceptor blockade is 30—45 min after stopping iv infusions. The dmg is hydrolyzed by tissue esterases and no active metabohtes of flestolol have been identified (41). 

Dlgltoxin. Digitoxin is a cardiac glycoside obtained from Digitalis purpurea. Digitoxin is indicated in the treatment of atrial flutter, atrial fibrillation, and supraventricular tachycardia. Its electrophysiologic and adverse effects are similar to those described for digoxin (87). 

The electrophysiological effects of amiodarone may be a composite of several properties. In addition to prolonging action potential duration and refractory period in ad tissues of the heart, the compound is an effective sodium channel blocker (49), calcium channel blocker (50), and a weak noncompetitive -adrenoceptor blocking agent (51). Amiodarone slows the sinus rate, markedly prolongs the QT interval, and slightly prolongs the QRS duration (1,2). 

The use of a bioadhesive, polymeric dosage form for sustained dehvery raises questions about swallowing or aspirating the device. The surface area is small, and patient comfort should be addressed by designing a small (less than 2 cm ), thin (less than 0.1 mm (4 mil) thick) device that conforms to the mucosal surface. The buccal route may prove useful for peptide or protein dehvery because of the absence of protease activity in the sahva. However, the epithelium is relatively tight, based on its electrophysiological properties. An average conductance in the dog is 1 mS/cm (57) as compared to conductances of about 27 and 10 mS/cm in the small intestine and nasal mucosa, respectively (58,59) these may be classified as leaky epitheha. 

Antiarrhythmic treatment is based upon modulation of the ionic currents mentioned above. A principal problem with this therapy is that the electrophysiology of all cells is targeted and not specifically the arrhythmogenic focus. As a consequence, all antiar-rhythmics acting at transmembrane ionic channels possess a risk for elicitation of arrhythmia (= proar-rhythmic risk). 

Further class IA drugs include the open state blockers procainamide and disopyramide with electrophysiolog-ical effects similar to those of quinidine procainamide lacks the antimuscarinic and antiadrenergic effects. Characteristic side effects of procainamide are hypotension and immunological disorders. 

Since alterations of thyroid fimction by amiodarone are related to the iodine substitution of the drug, the iodine-free derivative dronedarone has been developed with similar electrophysiological effects as amiodarone. It seems to act also as a T3-anatgonist, but does not provoke hyperthyreoidism [1]. 

The antimuscarinic drug atropine, and its derivative ipratropiumbromide, can also be used for antiarrhyth-mic treatment. Muscarinic receptors (M2 subtype) are mainly present in supraventricular tissue and in the AV node. They inhibit adenylylcyclase via G proteins and thereby reduce intracellular cAMP. On the other hand, activation of the M2 receptor leads to opening of hyperpolarizing Ik.acii and inhibits the pacemaker current If probably via the (3y-subunit of the Gi protein associated with this receptor. The results are hyperpolarization and slower spontaneous depolarization. Muscarinic receptor antagonists like atropine lead to increased heart rate and accelerated atrioventricular conduction. There are no or only slight effects on the ventricular electrophysiology. 

Intravenous administration of magnesium sulfate (1-5 g) is used for the termination of torsade de pointes arrhythmia. The underlying electrophysiological mechanism is not well understood. It includes changes of the current-voltage relationship of Iki and Ca2+ channel blockade. 

Clinical uses of antiarrhythmics have been restricted after CAST [2] due to their proarrhythmic risk, and preference is given to electrophysiological methods. 

Cardiac glycosides (CG) are potent and highly specific inhibitors of the intrinsic plasma membrane Na+/K+-ATPase, also known as the sodium pump. They modulate electrophysiological properties of the heart and its contractile functions. 

At a cellular level, the activation of mAChRs leads to a wide spectrum of biochemical and electrophysiological responses [1, 5]. The precise pattern of responses that can be observed does not only depend on the nature of the activated G proteins (receptor subtypes) but also on which specific components of different signaling cascades (e.g. effector enzymes or ion channels) are actually expressed in the studied cell type or tissue. The observed effects can be caused by direct interactions of the activated G protein(s) with effector enzymes or ion channels or may be mediated by second messengers (Ca2+, DP3, etc.) generated upon mAChR stimulation. 

Component of the myelin sheath surrounding the axons of nerve cells. Additional compounds of the myelin sheath are phospholipids, cholesterol, cerebrosides, and specific keratins. The myelin sheath constitutes an isolating barrier during electrophysiological axonal signaling. 

Rapid eye movement sleep. Sleep stage characterized by rapid movements of the eyes and asynchronous EEG activity in the theta-frequency (5-10Hz) range. Counterpart is slow wave sleep, characterized by other electrophysiological (synchronized low frequency l-2Hz, large amplitude EEG and neuronal sharp wave-ripple oscillations) and endocrine (growth hormone surge) activities. 

Electrophysiological studies (mainly using voltage-clamp and patch clamp) revealed the essential properties of the sodium channels kinetics of channel gating and selective ion permeation. Sodium channels are... 

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