Ventricular conduction

Describe the modified Vaughan-Williams classification of antiarrhythmic drugs, and compare and contrast the effects of available antiarrhythmic drugs on ventricular conduction velocity, refractory period, automaticity, and inhibition of specific myocardial ion channels. 

The autonomic nervous system exerts the primary control on heart rate. Because the sympathetic and parasympathetic systems have antagonistic effects on the heart, heart rate at any given moment results from the balance or sum of their inputs. The SA node, which is the pacemaker of the heart that determines the rate of spontaneous depolarization, and the AV node are innervated by the sympathetic and parasympathetic systems. The specialized ventricular conduction pathway and ventricular muscle are innervated by the sympathetic system only. 

Cardiovascular Bradycardia and arrhythmia (block of atrio-ventricular conduction) used as surrogate of drug-induced QT prolongation Milan et al. 224 Ulrike et al.225... 

Auricchio A, Kloss M, Trautmann SI, Rodner S, Klein H. Exercise performance following cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. Am. J. Cardiol. 2002 89 198-203. 

Stellbrink C, Breithardt OA, Franke A, et al. Impact of cardiac resynchronization therapy using hemodynami-cally optimized pacing on left ventricular remodeling in patients with congestive heart failure and ventricular conduction disturbances, [see comment]. J. Am. Coll. Cardiol. 2001 38 1957-65. 

IC Flecainide Propafenone Markedly decrease V, of phase 0, profoundly decrease ventricular conduction velocity, markedly inhibit inward sodium current. High potential for proarrhythmia. 

The electrocardiographic effects of moricizine include alterations in conduction velocity without an effect on the refractoriness of heart tissue. Moricizine enhances sinus node automaticity and prolongs sinoatrial and His-Purkinje intervals and the QRS. Moricizine prolongs ventricular conduction, thereby widening the QRS complex on the electrocardiogram. It has no significant effects on the QT interval. 

Trazodone overdose carries a risk of myocardial irritation in patients with preexisting ventricular conduction abnormalities. 

Luke RA, Saffitz JE Remodeling of ventricular conduction pathways in healed canine infarct border zones. J Clin Invest 1991 87 1594-1602. 

Local anesthetics block the sodium channels, are cardiac depressants, and bring about a ventricular conduction defect and block that may progress to cardiac and ventilatory arrest if toxic doses are given. In addition, these agents produce arteriolar dilation. Circulatory failure may be treated with vasopressors such as ephedrine, metaraminol (Aramine), or mephentermine (Wyamine). Artificial respiration and cardiac massage may also become necessary. Among the local anesthetics, only cocaine blocks the uptake of norepinephrine, causes vasoconstriction, and may precipitate cardiac arrhythmias. 

Redfern C, Degtyarev M, et al. 2000. Conditional expression of a Gi-coupled receptor causes ventricular conduction delay and a lethal cardiomyopathy. Proc Natl Acad Sci USA 97 4826-4831. 

Initial clinical work focused on a product that would be used to convert patients who were hospitalized for recent-onset AF as an alternative to a cardioversion procedure. Cardiome partnered with Fujisawa (now Astellas Pharmaceuticals) for the clinical development of a vernakalant (1), which produces robust AF conversion rates and none of the ventricular conduction abnormalities associated with less selective agents.35 By the close of 2009, vernakalant had been in 5 large trials and several smaller trials, including a total of over 1200 AF patients. Four Phase III studies—Atrial Arrhythmia Conversion Trials (ACT 1, 2, 3, and 4) —examined patients with recent onset AF (< 45 days) and the measured the rate of conversion to NSR in various periods after drug administration.36 38 The conversion rate was 45-63% in these studies, which tended to exclude patients with more compromised heart function or a history of heart failure. While there has been no specific study looking at QT prolongation, monitoring in both patients and in healthy volunteers showed only modest increases in the QT interval with no directly associated incidents of TDP across all trials. 

Freysz M., Timour Q., Mazze R. I., et al. (1989) Potentiation by mild hypothermia of ventricular conduction disturbances and reentrant arrhythmias induced by bupivacaine in dogs. Anesthesiology 70, 799-804. 

Short episodes of aberrant ventricular conduction and ventricular tachycardia occurred in three of 32... 

Cardiac beta-1 stimulation results in increases in sinoatrial rate, myocardial contractility, and increased atrial, atrioventricular node, and ventricular conduction velocity. Beta blockers decrease heart... 

Acute overdosage can result in both cardiovascular and neurologic effects. Ventricular dysrhythmias and hypotension are the most serious toxicities. Cardiac effects occur as a result of myocardial depression and depression of atrial, atrioventricular, and ventricular conduction. EKG changes will be evident. These EKG changes include a widening of the QT, PR, and QRS complexes ST depression and T inversion. Myocardial depression and vasodilation can cause hypotension to develop. Syncope can result from transient Torsade de Pointes (i.e., bursts of atypical ventricular tachycardia). Ventricular tachycardia and ventricular fibrillation may develop. Possible central nervous system (CNS) effects include lethargy, seizures, and coma. Other acute effects can include apnea. Signs of toxicity are expected to occur in... 

Prior to cellular excitation, an electrical gradient exists between the inside and the outside of the cell membrane. At this time, the cell is polarized. In atrial and ventricular conducting tissue, the intracellular space is about 80 to 90 mV negative with respect to the extracellular environment. The electrical gradient just prior to excitation is referred to as resting membrane potential (RMP) and is the result of differences in ion concentrations between the inside and the outside of the cell. At RMP, the cell is polarized primarily by the action of active membrane ion pumps, the most notable of these being the sodium-potassium pump. For example, this specific pump (in addition to other systems) attempts to maintain the intracellular sodium concentration at 5-15 mEq/L and the extracellular sodium concentration at 135-142 mEq/L and the intracellular potassium concentration at 135-140 mEq/L and the extracellular potassium concentration at 3-5 mEq/L. RMP can be calculated by using the Nemst equation ... 

Auricchio A, Stellbrink C, Butter C, et al. Clinical efficacy of cardiac resynchronization therapy using left ventricular pacing in heart failure patients stratified by severity of ventricular conduction delay. J Am Coll Cardiol 2003 42 2109-16. 

Auricchio A, Ding J, Spinelli JC, et al. Cardiac resynchronization therapy restores optimal atrioventricular mechanical timing in heart failure patients with ventricular conduction delay. 

Local anesthetics block the sodium channels, are cardiac depressants, and bring about a ventricular conduction defect and block that may progress to cardiac and ventilatory arrest if toxic doses are given. In addition, these agents produce... 

Flecainide, one of a classic membrane-stabilizing group of antiarrhythmic agents, decreases intracardiac conduction in all parts of the heart with the greatest effects being noted in the His-Purkinje system. Effects upon atrioventricular (AV) nodal conduction time and intra-atrial conduction time, although present, are less pronounced than those on the ventricular conduction system. 

Acetylcholine (ACh) decreases the rate of firing of the sinoatrial (SA) node (negative chronotropic effect) and the rate of conduction through the atrioventricular (AV) node and ventricular conduction system (negative dromotropic effect), resulting in bradycardia. The force of contraction of the heart muscle is also reduced (negative inotropic effect), resulting in decreased ejection fraction and decreased cardiac output. 

Supraventricular arrhythmias arising from accessory conduction pathways include Wolff-Parkinson-White syndrome (re-entrant arrhythmias). In this case, a depolarization and conduction occur in an accessory pathway, which circumvents the upper portion of the AV node and weakly depolarizes AV nodal tissue. Then, because the tissue is quickly repolarized, it is able to rapidly depolarize the upper portion of the AV node after depolarization of myocardial tissue, causing a re-entrant loop or circus rhythm. (The nodal tissue is normally refractory to stimulus, and thus serves as the termination stimulus for ventricular conduction.) The therapy of supraventricular arrhythmias involves partial blockade of the AV node. 

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