Conducting tissues, slow

The most frequently used classification system is that proposed by Vaughan Williams (Table 6-1). Type la drugs slow conduction velocity, prolong refractoriness, and decrease the automatic properties of sodium-dependent (normal and diseased) conduction tissue. Type la drugs are broad-spectrum antiarrhythmics, being effective for both supraventricular and ventricular arrhythmias. 

The slow Ca current in smooth muscle, nodal and conducting tissues. 

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). 

To be effective, this method must be carried out on samples which have been blanched, and upon peas from which the skins have been removed. The heat applied in blanching drives off gases entrapped in the tissues, and removal of the skins is required to remove air that may be entrapped under them, although it materially slows up the operation and makes it very tedious. In order that there may be consistency in grading, the test must be conducted under closely standardized conditions of temperature and solution concentration. This becomes of considerable importance in borderline cases, and failure to take it into consideration no doubt accounts for some of the inconsistency in results experienced by the industry. The test is not a true measure of tenderness, in that it accounts for variation in skin texture only in so far as maturity affects skin texture. Skin texture is affected by factors other than maturity (4). Other methods for the estimation of maturity based upon density or specific gravity have been suggested by Jodidi (16) and by Lee (22). 

The process of reentry is depicted in Fig. 6-3.4 Under normal circumstances, when a premature impulse is initiated, it cannot be conducted in either direction down either pathway because the tissue is in its absolute refractory period from the previous beat. A premature impulse may be conducted down both pathways if it is only slightly premature and arrives after the tissue is no longer refractory. However, when refractoriness is prolonged down one of the pathways, a precisely timed premature beat may be conducted down one pathway, but cannot be conducted in either direction in the pathway with prolonged refractoriness because the tissue is still in its absolute refractory period (Fig. 6-3, panel la).4 When the third condition for reentry is present, that is, when the velocity of impulse conduction in the other pathway is slowed, the impulse traveling forward down the other pathway still cannot be conducted. However, because the impulse in the other pathway is traveling so slowly, by the time it circles around and travels upward down the other pathway, that pathway is no longer in its absolute refractory period, and now the impulse may travel upward in that pathway. In other words,... 

O Paroxysmal supraventricular tachycardia is caused by reentry that includes the AV node as a part of the reentrant circuit. Typically, electrical impulses travel forward (antegrade) down the AV node and then travel back up the AV node (retrograde) in a repetitive circuit. In some patients, the retrograde conduction pathway of the reentrant circuit may exist in extra-AV nodal tissue adjacent to the AV node. One of these pathways usually conducts impulses rapidly, while the other usually conducts impulses slowly. Most commonly, during PSVT the impulse conducts antegrade through the slow... 

An internodal conduction pathway also extends from the SA node and transmits the impulse directly to the atrioventricular (AV) node. This node is located at the base of the right atrium near the interventricular septum, which is the wall of myocardium separating the two ventricles. Because the atria and ventricles are separated from each other by fibrous connective tissue, the electrical impulse cannot spread directly to the ventricles. Instead, the AV node serves as the only pathway through which the impulse can be transmitted to the ventricles. The speed of conduction through the AV node is slowed, resulting in a slight delay (0.1 sec). The cause of this AV nodal delay is partly due to the smaller fibers of the AV node. More importantly, however, fewer gap junctions exist between the cells of the node, which... 

Verapamil (Class IV antiarrhythmic drug) is an effective agent for atrial or supraventricular tachycardia. A Ca++ channel blocker, it is most potent in tissues where the action potentials depend on calcium currents, including slow-response tissues such as the SA node and the AV node. The effects of verapamil include a decrease in heart rate and in conduction velocity of the electrical impulse through the AV node. The resulting increase in duration of the AV nodal delay, which is illustrated by a lengthening of the PR segment in the ECG, reduces the number of impulses permitted to penetrate to the ventricles to cause contraction. 

It is known that 10B collects in brain tumors to a greater extent than in normal tissue. Research has been conducted on the use of the isotope 10B for treating brain tumors. Bombardment of the tumor with slow neutrons leads to the production of alpha particles (4He2+) and lithium nuclei that have enough energy to destroy the abnormal tissue. 

For the most part the selective Class III agents appear to act by inhibition of one or more repolarizing potassiuim currents, especially the delayed rectifier (/k) and/or the inward rectifier (/ki). Less selective agents generally affect sodium currents, as well as potassium currents, which translates to Class I (conduction-slowing) activity. Additional work still needs to be done to increase our understanding of the currents and channels involved in regulation of APD. Care must be taken to evaluate species differences, tissue dif-... 

Class rv drugs block the slow inward Ca current (L-type calcium channel) in cardiac tissue. The most pronounced electrophysiological effects are exerted on cardiac cells that depend on the Ca" " channel for initiating the action potential, such as those found in the sinoatrial and A-V nodes. The administration of class IV drugs slows conduction velocity and increases refractoriness in the A-V node, thereby reducing the ability of the A-V node to conduct rapid impulses to the ventricle. This action may terminate supraventricular tachycardias and can slow conduction during atrial flutter or fibrillation. 

The action potential duration and ERP of atrial muscle are both prolonged by propafenone. The electrophysiological effects persist beyond removal of the drug from the tissue. In patients with atrial flutter, fibrillation, or tachycardia, propafenone can slow the atrial rate, resulting in a change from 2 1 or 4 1 A-V block to 1 1 A-V conduction with a subsequent increase in the ventricular rate. 

Mechanism of Action A betaj-adrenergic blocker that competitively blocks beta,-adrenergic receptors in cardiac tissue. Reduces the rate of spontaneous firing of the sinus pacemaker and delays AV conduction. Therapeutic Effect Slows heart rate, decreases cardiac output, decreases BP, and exhibits antiarrhythmic activity. Pharmacokinetics ... 

Verapamil blocks both activated and inactivated L-type calcium channels. Thus, its effect is more marked in tissues that fire frequently, those that are less completely polarized at rest, and those in which activation depends exclusively on the calcium current, such as the sinoatrial and atrioventricular nodes. Atrioventricular nodal conduction time and effective refractory period are invariably prolonged by therapeutic concentrations. Verapamil usually slows the sinoatrial node by its direct action, but its hypotensive action may occasionally result in a small reflex increase of sinoatrial nodal rate. 

Amiodarone Blocks IKr, JNa/ Ica-L channels, adrenoceptors Prolongs action potential duration and QT interval slows heart rate and AV node conduction low incidence of torsade de pointes Serious ventricular arrhythmias and supraventricular arrhythmias Oral, IV variable absorption and tissue accumulation hepatic metabolism, elimination complex and slow Toxicity Bradycardia and heart block in diseased heart, peripheral vasodilation, pulmonary and hepatic toxicity hyper- or hypothyroidism. Interactions Many, based on CYP metabolism... 

What is the role of the gap junctions By coupling the myocardial cells in both directions (longitudinal and transverse) they are responsible for the biophysical properties of the tissue. A reduction in gap junction distribution or a closure of the gap junction channels causes nonuniformities and discontinuities which alter the biophysical properties of the tissue and make it more prone to nonuniform anisotropic reentry. According to the model proposed by Krinsky [1966], a reduction in gap junctions or a closure of gap junction channels will lead to local slowing of conduction, thereby allowing smaller perimeters of reentrant arrhythmia. In addition, slowing of conduction is generally believed to be a risk factor for initiation of reentry. Since in many... 

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