Chapter 14 Agents used in Cardiac Arrhythmias Cardiac arrhythmia • Approximately 50% of post-myocardial infarction fatalities result from ventricular tachycarida (VT) or ventricular fibrillation (VF). These fatal arrhythmias arise from mechanical dysfunction and ischemic events interacting within a disordered electrophysiological situation. Definition of arrhythmia • Arrhythmias and disrhythmias are the same thing. Cardiac arrhythmia is an abnormality of the heart rhythm. – Bradycardia – heart rate slow (<60 beats/min) – Tachycardia – heart rate fast (>100 beats/min) Categories of arrhythmias ↗sinus bradycardia ↗ Bradycardia Arrhythmias ↘A-V block ↘ Tachycardia atrial~, supraventricular ~, ventricular~ Cardiac Electrophysiology • To understand the action and classification of the antiarrhythmic drugs, it is first necessary to understand the ionic movements that underlie the Ca Ca2+ cardiac membrane potential. ss • The voltage change of the membrane potential is associated Ca Ca jsr nsr with the changes of ions across membrane, ie Na+, K+, and Ca2+ Inward Na and Ca Outward K Currents Currents Membrane Potential of Cardiac Cell There are two membrane potentials: resting potential and action potential. • The resting potential maintains approximately -80 to –90 mV • The action potential may be elevated to +10 to +20 mV Phases of action potential of cardiac cells A typical AP of ventricular muscle cell can be divided into 5 phases • Phase 0： rapid depolarisation Phase 1 – inflow of Na+ IV • Phase 1：partial repolarization Phase 2 – inward Na+ current deactivated, outflow 0 mV of K+ • Phase 2： plateau – slow inward calcium current III Phase 0 • Phase 3：rapid repolarisation I Phase 3 – calcium current inactivates, K+ outflow • Phase 4：pacemaker potential/diastole – Na+ outflow and K+ inflow by Na- KATPase -80mV Phase 4 – Autorhythmic cell : Na+ inflow to reach threshold potential II Fast and slow response In view of characteristics of 0.12-0.2 s approx. 0.44 s depolarization, cardiac action potentials are classified into slow and fast responses. SA • The action potential of normal node atrial, ventricular cell and His- Purkin-je fibers is typical fast atrial response. AV • Action potentials of SA and AV notes exemplify slow response under normal condition . ventricular Hispurkinje Fast responses • The fast response is characterized by a rapid phase 0 depolarization and a marked negative resting potential (-80 to -90 mV). • The depolarization of fast response is due to the rapid and intense inward flow of Na+ through voltage gated Na+ channels . Slow responses • The slow response is characterized by a slow rising phase 0 and a less negative resting potential in the range of -40 to -70 mV. • The phase 0 depolarization of slow response cardiac cell is elicited by the inward current of Ca2+ through L-type calcium channel.