Autocorrelation-based algorythm to detect alternans in calcium buffered ventricular myocytes.

Abstract

Both action potential (AP) alternans (AP-ALT) and intracellular calcium transient (CaT) alternans (CaT-ALT) are arrhythmogenic. Since AP and CaT are bidirectionally coupled, either signal's dynamic response theoretically affects alternans formation in its counterpart. It was shown that CaT-ALT do not require AP-ALT, but whether AP-ALT require CaT-ALT is not well known. Because in isolated myocytes AP-ALT readily change amplitude and persistence, we developed an autocorrelation-based algorithm to objectively detect AP-ALT, and used it to assess how removing CaT-ALT impacts AP-ALT formation. Tyrode perfused (37 oC) isolated rabbit ventricle myocytes were paced at progressively shorter pacing cycles lengths (BCL) from 500 ms to the shortest BCL>179 ms eliciting AP-ALT (>14 consecutive 2:2 activations), i.e. the alternans threshold (ALT-TH). We determined the AP duration (APD) of the last 40 APs at each BCL. The average cross-correlation between the original 40-APD sequence and its mathematically shifted equivalent (shifts equaled odd values 1-through-7) yielded the autocorrelation index (ACI). CaT was abolished using 20 mM BAPTA. 65% control myocytes were alternans positive. ACI ranged from 0 to −1 and correlated negatively with the duration of consecutive long-short APD sequences (alternans)(R=-0.9062, p<0.0001), thus effectively reporting the absence/presence of alternans. Versus controls, BAPTA increased the AP-ALT incidence and ALT-TH (65 vs 91%; 226±36 vs 273±56 ms, p<0.03), but did not change the ACI of alternans positive cells (0.07±0.09 vs 0.13±0.11 at 500 ms BCL; −0.66±0.17 vs −0.60±0.22 at ALT-TH; 2-way-ANOVA p>0.05 factor-group and p<0.0001 factor-BCL). Concomitantly, at ALT-TH BAPTA prolonged APD (225±52 vs 180±34 ms in control, p<0.02), but the diastolic interval remained unaltered. Our autocorrelation-based algorithm efficiently detects alternans. AP-ALT thrive in the absence of CaT and are more sensitive to activation rate changes. Therapies aiming to reduce CaT or its dynamic response should consider this.