Cardiac Reentry Arrhythmias and Antiarrhythmic Drug Mechanisms
Mechanisms of Reentry Arrhythmias
The following scenarios illustrate the development of reentrant arrhythmias:
- B: Interruption of Stimulus (Prolonged Refractory Period)
This represents the momentary interruption of the stimulus due to tissue damage that prolongs the refractory period. This tissue is not dead but exhibits a lengthening of the refractory period, perhaps due to localized hypoxia (lack of oxygen). The impulse in the right branch is interrupted, but the impulse in the left branch continues its normal path and does not vanish with the central branch, as seen in diagram A. This process happens in milliseconds, allowing the tissue time to potentially heal.
- C: Impulse Reentry During Recovery
Since these events happen in milliseconds, the tissue can recover and return to an enabled state for the passage of the impulse. The impulse that was not disrupted in B can now pass through the recovered tissue in C, generating impulse reentry. This leads to reentrant arrhythmia (D), which is a pathological condition.
Clinical Management of Reentry Arrhythmias
From a clinical point of view, doctors must determine if a Type I pathology of this kind is an abnormal impulse disorder or a condition of reentry.
Antiarrhythmic Drug Strategies
Antiarrhythmic drugs are used to counteract this situation, primarily by adjusting the refractory period:
- Shortening the Refractory Period: If the refractory period is unusually long, drugs can shorten it, re-establishing the normal circuit (similar to diagram A). Certain drugs act selectively in areas where there is a delay in the refractory period.
- Lengthening the Refractory Period: Another type of drug further extends the refractory period in the pathologically lengthened area. If the refractory period is extended sufficiently, it will block the reentry of the impulse.
These are the two primary ways of dealing with this disease. In summary, reentry arrhythmias involve a prolonged refractory period in a specific sector. Clinically, we can reverse this event by either normalizing the refractory period or further extending it to achieve block.
Note: Certain drugs may produce profound bradycardia. While technically this may be called dysrhythmia, in practice, we often use the term arrhythmia when referring to both a decrease (bradycardia) or an increase (tachycardia) in beats per minute.
Post-Depolarizations: EAD and DAD
Post-depolarizations are crucial mechanisms contributing to arrhythmia:
Early Afterdepolarizations (EAD)
EADs are depolarizations occurring during Phase 3, before the tissue has fully repolarized. This happens when the heart rate is relatively slow (low frequency), allowing a new discharge to occur before normalization.
Delayed Afterdepolarizations (DAD)
DADs occur in Phase 4 and correspond to a late depolarization phase. They are often triggered by factors like catecholamines and digitalis, and typically manifest clinically as an extrasystole.
Antiarrhythmic Effects on Spontaneous Firing
Antiarrhythmics aim to achieve a bradycardic effect by reducing spontaneous firing. The goal is to delay the onset of the second stimulus, displacing it to a later time. This correction is mediated by the drug’s effect on diastolic depolarization (Phase 4):
- Mechanism A: Slowing Phase 4 Depolarization
The drug slows Phase 4 diastolic depolarization, meaning it takes a longer time to reach the threshold. There is no modification of the threshold potential itself.
- Mechanism B: Changing the Threshold Potential
There is a change (lowering) in the threshold potential, while the rate of diastolic depolarization remains relatively unchanged.
- Mechanism C: Increasing Maximum Diastolic Potential (MDP)
The maximum diastolic potential becomes more negative (where the arrow is indicated). By increasing the MDP, the impulse is delayed, as it takes longer to travel the distance to the threshold. The threshold itself is not modified.
- Mechanism D: Increasing Action Potential Duration (APD)
The drug increases the duration of the action potential (PA). This lengthens the action potential and widens repolarization.