Key Points
- To determine whether ischemia-induced kinetic differences between membrane voltage and intracellular calcium transients drive cardiac vulnerability to repolarization alternans.
- Subjected Langendorff-perfused guinea pig hearts to 10–15 minutes of global no-flow ischemia followed by 10–15 minutes of reperfusion.
- Stained myocardium with rhod-2 AM and RH-237 to record action potentials and intracellular calcium transients simultaneously using a dual 16x16 photodiode optical mapping array.
- Ischemia shortened action potential duration (APD) with marked spatial heterogeneity, whereas intracellular calcium transient duration lengthened more uniformly via delayed upstroke, broader peaks, and slowed decay.
- Rapid pacing consistently triggered calcium transient alternans when action potential upstrokes preceded complete calcium relaxation, though sites with greater APD shortening exhibited little to no APD alternans.
- Spatial discordance between calcium transient alternans and APD alternans generated substantial spatial dispersion of repolarization across ischemic tissue.
Structured PICO
PPopulationPerfused Langendorff guinea pig hearts
IIntervention10-15 min of global no-flow ischemia followed by 10-15 min of reperfusion
OOutcomeChanges in action potential (AP) and intracellular calcium transient (Ca(i)T) resulting in alternanssurrogate
Contrasting effects of ischemia on the spatial distribution of action potential and calcium transient durations explain the vulnerability of the ischemic heart to electrical alternans.