Abstract 2626: Simultaneous Transmural Mapping of Voltage and Calcium in the Human Heart
Simultaneous measurements of both action potential (AP) and calcium transient (CaT) play an important role in studies of electro-mechanical coupling and mechanisms of cardiac arrhythmias but such measurements have not been performed in the human heart. Here, we report first results of optical mapping of the AP and CaT in coronary-perfused LV transmural wedge preparations from both failing (F) and non-failing (NF) human hearts. We mapped failing hearts (n=3, age 59±9), which were obtained during transplantation, and non-failing hearts (n=6, age 57±6), which were rejected from transplantation due to LV hypotrophy, history of ischemic heart disease, or age. LV wedge preparations were stained with fluorescence dyes RH237 and Rhod-2. Optical AP and CaT were simultaneously recorded at varying pacing rates by two precisely aligned CMOS cameras. The mean delay between AP and CaT upstrokes was transmurally uniform in both NF and F hearts; at 40 bpm (beat per minute), the mean delay was 8.3±1.6 ms and 8.4±1.7 ms in NF and F hearts, respectively. The delay prolonged upon rate acceleration. AP duration (APD) at 80% recovery at 40 bpm was significantly longer at the endocardium compared with the epicardium (409±60 vs. 367±48ms in NF; 474±56 vs. 437±54ms in F). Similarly, CaT durations at 80% recovery were significantly longer at the endocardium compared with the epicardium (495±42 vs. 426±37ms in NF; 583±67 vs. 509±77ms in F). The relaxation rate quantified by the time constant of a single exponential fit of CaT was significantly slower at the endocardium than at the epicardium (159±32 vs. 131±24ms in NF; 173±39 vs. 149±6ms in F). Increasing pacing rates reduced APD and CaT duration gradients and caused alternans of APD and CaT, which originated at the subendocardium. Alternans of delay between AP and CaT upstrokes were also observed. Western blots showed no significant difference in the expression of SERCA2 ATPase and phospholamban between endocardium and epicardium. In summary, we found the mean delay of 8.3±1.7ms between AP and CaT upstrokes. We also demonstrated a transmural gradient in AP and CaT duration and relaxation rate. SERCA2 ATPase and phospholamban do not appear to be responsible for the observed calcium transient kinetics gradient between endocardium and epicardium.