Related Experiment Videos
Rate dependence of ischaemic myocardial depolarisation: evidence for a novel membrane current
Insights
Myocardial ischemia causes cellular depolarization partly due to potassium loss. However, rapid heart rates reveal a potassium-independent mechanism worsening conduction and promoting arrhythmias.
Area of Science:
- Cardiology
- Electrophysiology
- Myocardial Ischemia Research
Background:
- Myocardial ischemia leads to cellular depolarization, primarily attributed to potassium ion (K+) loss.
- Unlike other ischemia manifestations, potassium loss is reportedly independent of heart rate.
Purpose of the Study:
- To investigate the relationship between cellular depolarization and extracellular potassium activity during myocardial ischemia under varying heart rates.
- To elucidate the mechanisms underlying depolarization during ischemia, particularly the role of potassium.
Main Methods:
- Utilized Langendorff perfused canine hearts subjected to serial coronary artery occlusions.
- Alternated occlusions between sinus rhythm (approx. 92 bpm) and rapid pacing (180 bpm).
- Measured cellular depolarization via TQ depression and extracellular potassium activity (ΔEK).
Main Results:
- At slow heart rates, potassium accumulation largely explained depolarization.
- During rapid pacing, a potassium-independent mechanism predominated, significantly increasing depolarization (324% in the first minute) with minimal ΔEK.
- This potassium-independent mechanism is crucial in the early stages of ischemia, especially at higher heart rates.
Conclusions:
- Ischemia induces a heart rate-sensitive depolarizing membrane current.
- This current exacerbates conduction abnormalities and increases the risk of arrhythmias during rapid pacing.
- Findings highlight a critical, rate-dependent mechanism in ischemic heart disease pathophysiology.
Abstract:
Depolarisation of ischaemic myocardial cells is at least partly due to loss of cellular potassium. Whereas most manifestations of ischaemia vary with heart rate potassium loss, however, reportedly does not. Cellular depolarisation was therefore correlated with extracellular potassium activity during serial coronary artery occlusions in Langendorff perfused canine hearts. Occlusions in sinus rhythm (92(11) beats X min-1) were alternated with rapidly paced occlusions (180 beats X min-1). For each occlusion cellular depolarisation was estimated from TQ depression and compared with the simultaneous increase in potassium electrode potential, delta EK. Although potassium accumulation accounted for most of the estimated depolarisation at slow heart rates, a potassium independent mechanism predominated during rapid pacing. The potassium independent mechanism was especially important in the first minute of ischaemia when pacing increased depolarisation by 324%, with little increase in delta EK. It appears that ischaemia induces a rate sensitive depolarising membrane current, which worsens conduction and promotes arrhythmias.