Spatial heterogeneity of calcium transient alternans during the early phase of myocardial ischemia in the blood-perfused rabbit heart

Background-Optical mapping of cytosolic calcium transients in intact mammal ian hearts is now possible using long-wavelength [Ca2+](i) indicators. We p ropose that beat-to-beat [Ca2+](i) transient alternans during ischemia may lead to spatial and temporal heterogeneity of calcium-activated membrane cu rrents. Methods and Results-To test this hypothesis, isolated rabbit hearts were lo aded with the fluorescent [Ca2+](i) indicator, rhod-2 AM, and imaged at 300 frames/sec during blood-perfused ischemic trials. High-quality [Ca2+](i) t ransients were recorded in each of 8 hearts. [Ca2+](i) transient alternans was never present in control records but occurred in each of the hearts dur ing ischemia, with onset after 2 to 4 minutes. Alternans was confined to ci rcumscribed regions of the heart surface 5 to 15 mm across. Multiple region s of alternans were found in most hearts, and regions that were out of phas e with one another were found in 6 hearts. Quantitative maps of alternans w ere constructed by calculating an alternans ratio. This ratio behaved as a continuous variable that reached a maximum value in the center of the regio ns with alternans. Conclusions-These results demonstrate marked spatial heterogeneity of the [ Ca2+](i) transient during the early phase of ischemia, which could produce electrical instability and arrhythmias in large mammalian hearts.