Abstract 2871: Optical Mapping of Failing Human Hearts Shows No Consistent M Cell Pattern With Prolonged Action Potential Duration and Ca2+Transient
Introduction: Abnormal intracellular Ca2+handling and prolongation of action potential duration (APD) are hallmark findings in failing hearts and can promote arrhythmias. Transmural differences in both APD and intracellular Ca2+transient (CaT) in pathological conditions have been described in many species but these phenomena are poorly understood in human hearts.
Methods: This study assessed transmural APD and CaT in tissues from 6 failing human hearts obtained at the time of heart transplant (mean age 57±7 years, 5 males; 4 ischemic and 2 non-ischemic cardiomyopathy). Transmural wedges were isolated from scar-free segments of the left ventricular free wall, perfused arterially, stained with a voltage sensitive dye (RH237), and loaded with a Ca2+indicator (Rhod-2 AM). Transmural APDs and duration of CaT (CaT90) during endocardial pacing at cycle lengths of 4000 ms were measured using an optical mapping system having a 16×16 photodiode array. We defined epicardium (Epi) and endocardium (Endo) as within 20% from the respective surface and divided the midmyocardium into 2 equal regions designated M1 (close to Epi) and M2 (close to Endo).
Results: The mean transmural APD was 527 ms (range 443–590 ms) and CaT90 629 ms (range 543–748 ms). The mean transmural dispersion of APD and that of CaT (longest minus shortest) was 93 ms (range 41–137 ms) and 288 ms (range 192– 411 ms), respectively. The pattern of transmural APD showed progressive prolongation from Epi (shortest) to Endo (longest) in 3 tissues, no obvious transmural change in 2 tissues, and M cell behavior (longest APD in M2) in one wedge. In contrast, the longest CaT90 was located in M1 in 4 tissues, in Epi in 1, in Endo in 1 tissue, and exceeded APD by 94 ms (range −47-+236 ms.
Conclusion: While M cell behavior was found in only 1/6 hearts, the longest CaT was noted in the subepicardium in 5/6 hearts. Such APD and CaT mismatch can be a mechanism of arrhythmogenesis in failing human hearts.