CARDIAC ARRHYTHMIAS

• What is an Arrhythmia?
  An abnormality of rate, regularity, or site of origin of the cardiac impulse or an alteration of the normal sequence of activation of atria and ventricles
  Common atrial tachyarrhythmias
  Atrial fibrillation (350-800 beats/mm); atrial contraction ineffective; 130-170 beats/mm transmitted to ventricle (irregularly) prior to treatment.
  Atrial flutter: regular rapid beating---250-300/min (effective contractions); 50% of impulses transmitted to ventricle.
  Paroxysmal atrial tachycardia (ca. 200 beats per mm); all impulses transmitted; usually terminates spontaneously and can occur in the absence of underlying disease
  Common ventricular arrhythmias
  Ventricular extrasystoles (premature beats): originate in ventricles; bizarre QRS, no P wave; premature interruption of dominant rhythm; possible cause--automaticity that arises in ectopic focus (likely to be within Purkinje system); often associated with acute phase of myocardial infarction or digitalis toxicity and may presage more serious dysrhythmias.
  ventricular tachycardia: 150-200 beats per mm; can produce circulatory impairment, congestive heart failure and severe hypotension.
  Abnormal automaticity
• Depolarized atrial, ventricular, or Purkinje fibers (beyond -60 mV) will cause phase 4 depolarization and spontaneous firing; such cells could become abnormal pacemakers.
• Abnormal automaticity facilitated by catecholamines
  Triggered activity
  Definition: the generation of impulses by afterdepolarizations that reach threshold (this can also occur in cells that ordinarily are incapable of automatic activity).
  Early afterdepolarization: repolarization is interrupted by secondary depolarizations that may excite neighboring fibers and be propagated; experimentally induced by stretching, hypoxia.
  Delayed afterdepolarization: after full repolarization occurs, Vm again transiently depolarizes; if the delayed afterdepolarization reaches threshold a premature propagated response will occur; experimentally induced by high concentrations of catecholamines or digitalis
  RE-ENTRY
  Definition: recirculating activations incited by an initiating depolarization

Required conditions

• unidirectional block
• slow conduction
• length of loop > ERP X Conduction Velocity
• heterogeneity of impulses
  Therapeutic aspect of antiarrhythmics: convert unidirectional block into bidirectional block; extend ERP of APs.
  Slow conduction in depressed area of heart mediated by depressed fast APs and/or slow (Ca-mediated) APs (Class I vs. Class IV antiarrhythmic agents).
  Depressed fast APs and slow APs exhibit post-repolarization refractoriness---a situation that predisposes to re-entry
  ANTIARRHYTHMIC AGENTS
  Class I: Na channel blockers (and K channels to some extent)
• examples: quinidine, procainamide, disopyramide, lidocaine, phenytoin (diphenylhydantoin)
• Depress phase 0 of fast AP
• quinidine, procainamide and disopyramide prolong repolarization and ERP
• quinidine depresses phase 4 depolarization and thus reduced automaticity
• phenytoin particularly useful against digitalis-induced ventricular arrhythmias
  Class II: beta-adrenergic blockade
• example: propranolol
• counteract (by competitive block) effects of norepinephrine, epinephrine (i.e., production of slow responses and enhanced automaticity)

• examples: bretylium, amiodarone
• bretylium has been used as a "chemical defibrillator" when arrhythmia is resistant to standard methods
  Class IV: Calcium channel blockers
• examples: verapamil, diltiazem, nifedipine
• block slow responses; slows A-V conduction (digitalis has similar effect by unknown mechanism)--hence useful to control impulse traffic in atrial tachyarrhythmias)