Increased delay in heart electrical conduction

Prolonged atrioventricular (AV) conduction time, also referred to as first-degree AV block, occurs when there is an abnormal delay in the conduction of electrical impulses from the atria to the ventricles via the AV node or the His-Purkinje system. This delay is characterized by a longer-than-normal PR interval on an electrocardiogram (ECG), typically exceeding 200 milliseconds in adults.

Electrocardiogram (ECG) Findings

Prolonged PR Interval: >200 ms (in adults), reflecting delayed conduction through the AV node.

Normal P-wave to QRS relationship: Every P wave is followed by a QRS complex.

Holter Monitoring

Used to evaluate intermittent or progressive AV conduction abnormalities.

Electrophysiology Study (EPS)

Provides detailed mapping of conduction pathways for diagnostic clarification in complex cases.

Blood Tests

Evaluate potential reversible causes (e.g., electrolyte levels, thyroid function).

Electrophysiological Studies

a. Patch-Clamp Recording

Purpose: Measures ionic currents and action potentials in single AV nodal cells.

Key Measurements:

Action Potential Duration (APD): Prolonged APD can contribute to delayed conduction.

Ion Currents:

Calcium Current (ICa): Reduced L-type Ca²⁺ channel activity delays depolarization in the AV node.

Potassium Currents (IK): Altered repolarization currents (e.g., delayed rectifier K⁺ currents) may slow conduction.

Funny Current (If): Dysfunctional pacemaker currents may indirectly affect conduction timing.

Application: Provides detailed insights into the contribution of ion channel dysfunction to conduction delay.

Microelectrode Studies

Purpose: Measures transmembrane potentials in tissue slices or isolated nodal regions.

Key Features:

Detects conduction delay between atrial and ventricular regions.

Identifies specific regions within the AV node where delay occurs.

Optical Mapping

Purpose: Visualizes electrical activity across cardiac tissue at the cellular level.

Key Method:

Use voltage-sensitive dyes to record changes in membrane potential.

Tracks conduction velocity across the AV node and surrounding regions.

Application: Identifies areas of delayed conduction or functional block in the AV node.

Molecular and Cellular Analysis

a. Ion Channel Expression Studies

Purpose: Assesses the expression and function of ion channels critical for AV node conduction.

Key Techniques:

qPCR and Western Blot: Quantify the expression of ion channels like:

L-type Ca²⁺ channels (Cav1.2): Key for depolarization in AV node cells.

HCN Channels: Contribute to pacemaker activity.

Potassium Channels (e.g., Kv, Kir): Involved in repolarization.

Immunostaining: Localizes ion channels in AV nodal cells.

Relevance: Reduced expression or dysfunction of these channels correlates with conduction delays.

b. Connexin Analysis

Purpose: Evaluates gap junction proteins (e.g., Connexin 43, Connexin 45) responsible for cell-to-cell conduction.

Techniques:

Immunohistochemistry or confocal microscopy.

Genetic or pharmacological modulation of connexin function.

Relevance: Decreased gap junction connectivity slows conduction velocity.

Cellular Calcium Handling

Purpose: Measures intracellular calcium transients critical for AV nodal conduction.

Key Method:

Use calcium-sensitive fluorescent dyes (e.g., Fluo-4, Fura-2).

Relevance: Impaired calcium cycling (e.g., reduced Ca²⁺ channel activity) slows depolarization and conduction.

Tissue-Level Functional Studies

AV Node Tissue Slices:

Isolated tissue preparations allow for measurement of conduction delays using extracellular electrodes or optical mapping.

Langendorff-Perfused Hearts:

Enables study of the whole heart, including AV node function, under controlled conditions.

Genetic and Pharmacological Modulation

a. Genetic Models

Knockout or Transgenic Mice: Models with specific ion channel or connexin mutations (e.g., HCN4, Cav1.3) help study the cellular basis of AV conduction delay.

b. Drug Studies

Calcium Channel Blockers (e.g., Verapamil): Induce AV conduction delay to study mechanisms.

Beta-adrenergic Agonists (e.g., Isoproterenol): Test enhancement of AV conduction.

Computational Modeling

Purpose: Simulates ionic currents, action potential propagation, and AV node conduction at the cellular level.

Relevance: Predicts how molecular or cellular changes contribute to prolonged conduction.

Causes of Prolonged AV Conduction Time

1. Intrinsic Factors

   • Age-related degeneration: Fibrosis or sclerosis of the conduction system.
   • Congenital heart disease: Structural abnormalities affecting conduction pathways.
   • Primary conduction system disease: Diseases like Lev's or Lenegre's disease.

2. Extrinsic Factors

   • Medications: Drugs that slow AV node conduction, such as:
     • Beta-blockers.
     • Calcium channel blockers (non-dihydropyridines like verapamil and diltiazem).
     • Digoxin.
     • Antiarrhythmics (e.g., amiodarone).
   • Electrolyte imbalances: Hyperkalemia or hypokalemia affecting conduction.
   • Autonomic factors: Increased parasympathetic (vagal) tone.

3. Cardiac Conditions

   • Ischemic heart disease (e.g., myocardial infarction involving the AV nodal artery).
   • Myocarditis or infiltrative diseases (e.g., sarcoidosis, amyloidosis).
   • Valvular heart disease (e.g., calcification of the mitral or aortic valve).

4. Systemic Causes

   • Infections such as Lyme disease or Chagas disease.
   • Endocrine disorders like hypothyroidism.

Clinical Presentation

• Asymptomatic: Often detected incidentally during ECG.
• Symptomatic (rare):
  • Fatigue.
  • Lightheadedness.
  • Syncope (if associated with progression to higher-degree AV block).

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