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Simultaneous maps of optical action potentials and calcium transients in guinea-pig hearts: mechanisms underlying concordant alternans

Bum-Rak Choi and Guy Salama

1. The mechanisms underlying electro-mechanical alternans caused by faster heart rates were investigated in perfused guinea-pig hearts stained with RH237 and Rhod-2 AM to simultaneously map optical action potentials (APs) and intracellular free Ca²⁺ (Ca²⁺_i).

2. Fluorescence images of the heart were focused on two 16 × 16 photodiode arrays to map Ca²⁺_i (emission wavelength (_em) = 585 ± 20 nm) and APs (_em > 715 nm) from 252 sites. Spatial resolution was 0·8 mm × 0·8 mm per diode and temporal resolution 4000 frames s^-1.

3. The mean time-to-peak for APs and [Ca²⁺]_i was spatially homogeneous (8·8 ± 0·5 and 25·6 ± 5·0 ms, respectively; n = 6). The durations of APs (APDs) and Ca²⁺_i transients were shorter at the apex and progressively longer towards the base, indicating a gradient of ventricular relaxation.

4. Restitution kinetics revealed increasingly longer delays between AP and Ca²⁺_i upstrokes (9·5 ± 0·4 to 11·3 ± 0·4 ms) with increasingly shorter S1-S2 intervals, particularly at the base, despite nearly normal peak [Ca²⁺]_i.

5. Alternans of APs and Ca²⁺_i transients were induced by a decrease in cycle length (CL), if the shorter CL captured at the pacing site and was shorter than refractory periods (RPs) near the base, creating heterogeneities of conduction velocity.

6. Rate-induced alternans in normoxic hearts were concordant (long APD with large [Ca²⁺]_i) across the epicardium, with a magnitude (difference between odd-even signals) that varied with the local RP. Alternans were initiated by gradients of RP, producing alternans of conduction that terminated spontaneously without progressing to fibrillation.

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