Introduction 13 25 2 28 38 7 33 52 10 45 15 49 1 34 39 46 47 64 12 14 21 24 32 22 8 31 37 2+ 35 44 54 55 12 30 57 6 36 48 19 23 18 40 42 temporal short 40 41 spatial long 55 58 63 20 26 Taken together, these novel findings implicate a dynamic component to arrhythmic substrate under conditions of hypokalaemia for which restitution may furnish a possible underlying mechanism. Materials and methods Experimental animals Mice were housed at 21 ± 1°C with 12-h light/dark cycles, were fed sterile chow (RM3 Maintenance Diet, SDS, Witham, Essex, UK) and had free access to water. Wild-type 129 Sv mice aged 3–6 months were used in all experiments. All procedures complied with the UK Animals (Scientific Procedures) Act 1986. Solutions 3 2 4 2 2 2 2 + Preparation 3 Electrophysiological measurements 5 Experimental protocol 19 dynamic pacing protocol 9 90 P Results 41 + + 21 Alternans and arrhythmic activity occur in hypokalaemic hearts paced at a reduced baseline cycle length 23 1 1 P 1 P 1 6 41 42 48 Fig. 1 + a + b c d A B C Vertical lines  Electrophysiological waveforms after the initiation of arrhythmic activity 16 58 63 4 16 2 A 2 A 2 Fig. 2 + A B a b  B 2 B 2 Alternans occurs in the epicardia and endocardia of hypokalaemic hearts paced at a baseline cycle length of 70 ms C 1 3 90 Fig. 3 filled bars open bars 90 a b + A + B C D  90 P 90 P P 90 P 90 P The dynamic pacing protocol initiates alternans in hypokalaemic hearts at short baseline cycle lengths 21 90 4 5 4 y x 5 4 5 4 5 Fig. 4 + a + b c d Vertical lines  Fig. 5 90 + a + b c d Filled open circles Arrow y x broken line  Alterations in the slopes of restitution curves correlate with pro- and anti-arrhythmic effects 90 90 21 29 32 55 90 90 6 A 6 B Fig. 6 90 DI circles A squares B + a + b c d 90 solid lines broken lines Shaded boxes  90 A B 6 A B 6 90 underestimation A B 6 A B 6 Restitution curves yield parameters predictive of arrhythmogenicity 13 1 \documentclass[12pt]{minimal}
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\begin{document}$$ \chi ^{2}_{R}  $$\end{document} P P These parameters also predict the anti-arrhythmic effect of lidocaine P 7 A τ \documentclass[12pt]{minimal}
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\begin{document}$$ \chi ^{2}_{R}  $$\end{document} P P Slopes of restitution curves thus precisely correlate with the presence or absence of alternans and arrhythmogenesis under all the conditions explored in the hypokalaemic Langendorff-perfused murine heart. Discussion 2 25 28 38 7 33 52 39 46 47 49 64 29 14 21 24 29 32 2+ 35 44 54 53 56 55 I Kr 27 61 59 11 + 17 62 19 23 18 40 42 temporal 40 41 spatial 26 50 I Kr I Ks I to 2 + 6 11 16 + I Na,f 4 + 7 1 3 8 5 10 2 7 33 38 52 29 55 8 31 37 43 63 51 16 58 9 60