Ventricular refractory period

Dantrolene is the mainstay of MH treatment. It has long been available for the treatment of muscle spasm in cerebral palsy and similar diseases. It is a hydantoin derivative that was first synthesized in 1967, and reported to be effective in the treatment of porcine MH in 1975. Also in 1975, dantrolene was shown to be more effective than procainamide in the treatment of human MH, which until that time was the drug of choice. However, the intravenous preparation was not made available until November 1979. It significantly lowered mortality. The half-life of dantrolene is estimated to be 6-8 hr. Dantrolene s primary mode of action is the reduction in calcium release by the sarcoplasmic reticulum. Dantrolene also exerts a primary antiarrhythmic effect by increasing atrial and ventricular refractory periods. Side effects of dentrolene include hepatotoxicity, muscle weakness, ataxia, blurred vision, slurred speech, nausea, and vomiting. Dantrolene is not contraindicated in pregnancy, but it does cross into breast milk and its effect on the neonate is unknown. 

The Class III effects of amiodarone develop over several weeks. This time-course is similar to that seen in thyroid gland ablation [25]. It is well known that patients with hypothyroidism have long QT intervals which are indicative of prolonged action potentials. Amiodarone has been shown to inhibit the conversion of thyroxine (T4) to triiodothyronine (T3) both in human subjects [26] and in vitro [27]. It has been argued that the Class III effects of amiodarone are due to its effects on thyroid hormones [28]. Others, however, argue that there is no relationship between prolongation of ventricular refractory period by amiodarone and thyroid state [29]. 

Mechanism of Action An antiarrhythmicthat prolongs both atrial and ventricular action potential duration and increases the atrial and ventricular refractory period. Activates slow, inward current (mostly of sodium), produces mild slowing of sinus node rate and AV conduction, and causes dose-related prolongation of QT interval. Therapeutic Effect Converts arrhythmias to sinus rhythm. 

Erythromycin has antidysrhythmic properties similar to those of Class lA antidysrhythmic drugs, and causes an increase in atrial and ventricular refractory periods. This is only likely to be a problem in patients with heart disease or in those who are receiving drugs that delay ventricular repolarization (5). High-doses intravenously have caused ventricular fibrillation and torsade de pointes (6). Each episode of dysrhythmia, QT interval prolongation, and myocardial dysfunction occurred 1-1.5 hours after erythromycin infusion and resolved after withdrawal. 

The WI mode is characterized by sensing and pacing in the ventricle so that pacing will occur when no intrinsic ventricular activity has occurred within a specified interval defined by the LRL. There are four intervals in the WI pacing mode VV, VR, RV, and RR where R is an intrinsically sensed R wave and V is a ventricular-paced event. VVI pacemakers have three basic timing cycles that must be considered LRL, hysteresis rate, and the ventricular refractory period. 

Fig. 3.10 Example of WI pacing from Fig. 3.2 with refractory periods added. The ventricular refractory period (VRP) has an initial absolute blanking period (solid black). During the absolute blanking period, no sensed events are noted in the marker channel. During the remaining portion of the VRP, the relative lefiactory period (gray), sensed events may be noted, but the LRL will not be reset.

The PR interval represents the time required for electrical impulse conduction from its origin at the onset of atrial depolarisation through the atrial conduction system to the ventricular myocardium. It generally represents conduction time across the AVN. Changes in this interval, in most species, reflect changes in Ca " channel function however, in the rat Na" channels are dominant (Botting et al. 1985). Unlike the PR interval, the QT interval represents the ventricular refractory period and includes depolarisation and repolarisation of ventricular muscle. In contrast to the atria, the AP in ventricular tissue is long ( 300 ms), which is a time interval that is similar to the duration of the QT interval. Thus, the QT interval is an approximate measure of ventricular repolarisation and thus channel function. 

Sensing in an ICD is quite dissimilar to that in a pacemaker. Why Recall that the R wave signals of a typical pacemaker system may fall between about 5-25 millivolt (mV). In contrast, an ICD needs to be able to detect VF wavelets that may be of very small amplitude, on the order of tenths of a millivolt. Simply setting a fixed sensitivity level at such a low level in an ICD without any other adjustments would likely cause T wave oversensing in any baseline rhythm. A ventricular refractory period would not solve this issue as the ICD needs to be alert during this time period for any tachycardia events. 

Indeca.inide. Indecainide hydrochloride is a po active antiarrhythmic agent that received PDA approval in 1989, but it has not been marketed as of this writing. Chemically, it is 9-[3-(isopropylamino)propyl]fiuorine-9-carboxamide [74517-78-5]. The dmg has potent activity against premature ventricular complexes (PVCs) and ventricular tachycardias. Indecainide has no effect on sinus node function, atrial or ventricular effective refractory periods (32,33). 

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. 

O Ventricular tachycardia is usually initiated by a precisely timed VPD, occurring during the relative refractory period, which provokes reentry within ventricular tissue. 

The effective refractory period is followed by a relative refractory period that lasts for the remaining 50 msec of the ventricular action potential. During this period, action potentials may be generated however, the myocardium is more difficult than normal to excite. 

Procainamide (Class IA antiarrhythmic drug) is an effective agent for ventricular tachycardia. Its mechanism of action involves blockade of the fast Na+ channels responsible for phase 0 in the fast response tissue of the ventricles. Therefore, its effect is most pronounced in the Purkinje fibers. The effects of this drug s activity include a decrease in excitability of myocardial cells and in conduction velocity. Therefore, a decrease in the rate of the phase 0 upstroke and a prolonged repolarization are observed. As a result, duration of the action potential and the associated refractory period is prolonged and the heart rate is reduced. These effects are illustrated by an increase in the duration of the QRS complex. 

Propranolol slows heart rate, increases the effective refractory period of atrioventricular ganglia, suppresses automatism of heart cells, and reduces excitability and contractibihty of the myocardium. It is used for supraventricular and ventricular arrhythmias. Synonyms of this drug are anaprilin, detensiel, inderal, novapranol, and others. 

Pharmacology Therapeutic concentrations of lidocaine attenuate phase 4 diastolic depolarization, decrease automaticity and cause a decrease or no change in excitability and membrane responsiveness. Action potential duration and effective refractory period (ERP) of Purkinje fibers and ventricular muscle are decreased, while the ratio of ERP to action potential duration is increased. Lidocaine raises ventricular fibrillation threshold. AV nodal conduction time is unchanged or shortened. Lidocaine increases the electrical stimulation threshold of the ventricle during diastole. 

A. Class la Lengthens duration of action potential (t the refractory period in atrial and ventricular muscle, in SA and AV conduction systems, and Purkinje fibers)... 

In the undamaged myocardium, cardiac impulses travel rapidly antegrade through the Purkinje hbers to deliver the excitatory electrical impulse to the ventricular myocardium. During the normal activation sequence, retrograde conduction from ventricular myocardium to the conducting hbers is prevented by the longer duration of the membrane action potential and thus the refractory period in the Purkinje hbers. 

K, clecrease in conduction velocity I, increase in conduction velocity —, no known conduction effects APD, action potential duration ERP, effective refractory period (ventricular). 

The dominant effect on ventricular myocardium that has been chronically exposed to either amiodarone or desethylamiodarone is a prolongation in the action potential with an associated increase in the refractory period and a modest decrease in Vmax as a function of stimulus frequency. Amiodarone inhibits the delayed outward potassium current, a finding consistent with the observation of a prolonged action potential. Both amiodarone and its metabolite significantly decrease the ac-... 

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