Directly Damaging Cardiac Factors
Pathogenic agents causing primary damage to the heart muscle are divided into physical, chemical, and biological factors.
Physical factors include:
- Extracardiac heart compression (exudate accumulation in pericarditis, blood in hemopericardium and cardiac tamponade, pressure from tumors or emphysematous lungs).
- Electrical current exposure (household electrical injuries or medical defibrillation).
- Mechanical trauma (chest contusions, penetrating wounds, surgical complications).
Among chemical factors, the following are distinguished:
- Non-pharmacological compounds: heavy metal and calcium salts, enzyme inhibitors, lipid hydroperoxides, and uncouplers of oxidative phosphorylation.
- Medications in inappropriate dosages: cardiac glycosides, beta-blockers, calcium channel blockers.
- Deficiency states: lack of oxygen (hypoxia) or essential ions for metabolism.
Functional Overload and Heart Failure
Excessive myocardial strain is a leading cause of heart failure (HF). Functional overload is divided into two categories:
- Increased preload — heart overload due to excessive blood volume.
- Increased afterload — overload due to pressure (resistance to ejection).
Depending on the ratio of damage to overload, three forms of failure are distinguished:
- Myocardial — caused by primary damage to the cardiomyocytes themselves.
- Overload — occurs under excessive functional load on an initially intact (healthy) myocardium.
- Mixed — combines elements of direct damage and hemodynamic overload.
Role of Potassium and Acidosis in Arrhythmogenesis
During cell damage, a massive efflux of $K^+$ ions into the interstitial fluid occurs. This is driven by three factors: energy deficit (lack of ATP and creatine phosphate), ion pump dysfunction (decreased activity of plasmalemmal $K^+, Na^+$-ATPase), and structural damage (abnormal membrane permeability).
Extracellular potassium excess triggers a cascade of electrophysiological disruptions:
- Excitability threshold decreases due to a reduction in resting membrane potential (partial membrane depolarization).
- Impulse propagation slows down, generating an electrical current of injury in micro-regions of the tissue.
- Arrhythmogenic vulnerability increases: the refractory period shortens, and the myocardium recovers excitability faster, creating conditions for ectopic foci and re-entry waves.
A similar, though less pronounced, arrhythmogenic effect is produced by hydrogen ion ($H^+$) excess during tissue acidosis.
cAMP Accumulation and Arrhythmia Mechanisms
Intracellular cyclic AMP (cAMP) excess is a crucial factor in the development of arrhythmias. It accumulates due to two mechanisms:
- Activation of adenylate cyclase by catecholamines (epinephrine, norepinephrine).
- Inhibition of phosphodiesterases (cAMP-degrading enzymes) during ischemia, myocarditis, or cardiomyopathies.
High cAMP levels stimulate the slow inward calcium current ($I_{Ca}$), which overloads cardiomyocytes with calcium and induces triggered activity.
Ultimately, two main mechanisms of arrhythmias form:
- Abnormal automaticity (early or delayed afterdepolarizations).
- Circulation of the excitation wave (Re-entry), which can manifest as retrograde conduction, wave "reflection," or longitudinal dissociation.