Fig. 5.

PARP1 inhibitors significantly attenuated tachypacing-induced electrophysiological deterioration in HL-1 cardiomyocytes. a–h Optical voltage mapping of HL-1 cardiomyocyte monolayers following 1-Hz electrical stimulation in control nonpaced (NP) or 8 h tachypaced (TP) HL-1 cardiomyocytes with 20 µM olaparib, 40 µM ABT-888 or vehicle DMSO 12-h pretreatment before tachypacing. a Representative filtered optical signal traces. To indicate electrical heterogeneity, three tracers which vary in time and space [1 and 3] to excitation block [2] in the TP DMSO group are depicted b typical APD₃₀ and c APD₈₀ maps for indicated groups. d–h Corresponding quantitative analysis of APD₃₀, APD₈₀, APD₃₀ dispersion, APD₈₀ dispersion and excited cell surface area, showing that TP resulted in significant APD prolongation (a, d, e), an increase in APD dispersion (b, c, f, g) and a significant decrease of excited cell surface area (h) in HL-1 cardiomyocyte monolayers. Pretreatment of HL-1 cultures with ABT-888 or olaparib significantly prevented the tachypacing-induced electrophysiological deteriorations (a–h). ^***P < 0.001 vs. DMSO NP, ^###P < 0.001 vs. DMSO TP. n = 11 for NP DMSO, n = 9 for NP olaparib TP, n = 11 for NP ABT-888, n = 6 for TP DMSO, n = 6 for TP olaparib, n = 6 for TP + ABT-888. n = number of experiments. Data are all expressed as mean ± s.e.m. Individual group mean differences were evaluated with the two-tailed Student’s t test