Activated human platelet products induce proarrhythmic effects in ventricular myocytes

Area of Science:

• Cardiovascular Physiology
• Cardiac Electrophysiology
• Platelet Biology

Background:

• Sudden cardiac death, often due to ventricular fibrillation (VF) during ischemia, is a major cause of mortality.
• Platelet activation is implicated in increasing VF susceptibility in ischemic heart tissue, but the underlying mechanisms are unclear.

Purpose of the Study:

• To investigate the effects of activated blood platelet products (ABPPs) on cardiac electrophysiology and intracellular calcium (Ca(2+)(i)) homeostasis.
• To elucidate the cellular mechanisms by which ABPPs may contribute to arrhythmias in ischemic conditions.

Main Methods:

• Human platelets were activated, and secreted products (ABPPs) were applied to isolated rabbit ventricular myocytes.
• Electrophysiological properties (membrane potential) and Ca(2+)(i) transients were measured using patch-clamp and indo-1 fluorescence.
• Specific ion channel currents, including L-type Ca(2+) current (I(Ca,L)), were analyzed.

Main Results:

• ABPPs prolonged action potential duration and induced early and delayed afterdepolarizations.
• ABPPs significantly increased I(Ca,L) density and enhanced systolic Ca(2+)(i), Ca(2+)(i) transient amplitude, and sarcoplasmic reticulum Ca(2+) content.
• Other major ion currents and Na(+)-Ca(2+) exchange current remained unaffected.

Conclusions:

• Secreted products from activated human platelets alter cardiac electrophysiology by modulating I(Ca,L) and Ca(2+)(i) homeostasis.
• These alterations lead to action potential prolongation and afterdepolarizations, which may promote reentrant arrhythmias in scenarios like coronary thrombosis.