Simultaneous Maps of Optical Action Potentials and Calcium Transients in Guinea-pig Hearts: Mechanisms Underlying Concordant Alternans

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 x 16 photodiode arrays to map Ca2+i (emission wavelength (lamdda;em) = 585 +/- 20 nm) and APs (lamdda;em > 715 nm) from 252 sites. Spatial resolution was 0.8 mm x 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.