Introduction 12 23 41 52 2 36 44 21 37 1 36 44 45 T peak T end 54 33 T peak T end 53 40 28 proarrhythmic decrease antiarrhythmic increase Materials and methods Experimental animals Mice were housed in an animal facility at 21 ± 1°C with 12 h light/dark cycles. Animals 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 the experiments. All procedures complied with UK Home Office regulations (Animals [Scientific Procedures] Act 1986). Solutions 3 2 4 2 2 2 2 + Preparation 4 Electrophysiological measurements 9 Experimental protocol 30 90 43 22 P Modeling 16 18 6 + + 24 17 + + + + + + K1 to + 29 90 Results After-depolarizations initiate arrhythmic activity in bradycardic hypokalemic hearts + n + n n n 1 11 P Fig. 1 + a + b c d  1 P 1 1 P P 1 Extrasystolic stimulation immediately after recovery from refractoriness initiates arrhythmic activity in hypokalemic hearts 43 22 2 Fig. 2 A B C + a + b c d Single vertical lines double lines  2 n 2 n just after  recovery from refractoriness 2 2 2 n 2 n Arrhythmic tendency in hypokalemia correlates with increased local critical intervals 90 2 90 90 90 3 4 3 4 90 P 90 P 3 4 n 90 P 3 4 n P Fig. 3 + A + B C D 90 vertical solid lines vertical broken lines shading a 90 dense hashing sparse hashing shading b Asterisks P daggers  Fig. 4 + A + B C D 90 vertical solid lines vertical broken lines shading a 90 dense hashing sparse hashing shading b Asterisks P daggers  90 + 90 6 + + 24 + + K1 to 29 5 5 5 90 90 7 20 90 5 + 90 5 + K1 to 90 5 Fig. 5 + A + 90 vertical solid lines vertical broken lines shading a B C + K1 to 90 dense hashing sparse hashing shading b  The abolition of arrhythmic tendency by lidocaine correlates with negative shifts in local critical intervals 3 4 P 90 P n P 3 4 90 90 P n P Arrhythmic tendency in hypokalemia also correlates with increased transmural critical intervals 6 7 6 7 90 P 6 90 7 90 Fig. 6 90 vertical solid lines vertical broken lines shading + A + B C D Horizontal arrows a 90 dense hashing sparse hashing horizontal hashing shading b Asterisks P daggers  Fig. 7 90 vertical solid lines vertical broken lines shading + A + B C D Horizontal arrows a 90 dense hashing sparse hashing horizontal hashing shading b Asterisks P daggers  P 6 7 P P 6 7 The abolition of arrhythmic tendency by lidocaine also correlates with significantly decreased transmural critical intervals P 6 7 P P 6 7 Arrhythmogenesis occurs in the absence of significant alterations in the TDR 90 2 8 8 (P n 8 P 8 n 8 n Fig. 8 up-sloping hashing down-sloping hashing open bars + A + B C D Asterisks P  90 Discussion 52 23 42 12 41 2 1 3 37 10 13 46 51 2+ 27 35 2+ + + 2+ 47 2+ 2+ 26 10 13 46 51 43 22 14 38 48 30 15 31 39 + o 90 90 90 + o + 90 + o decreased 90 + o 19 + o + K1 to 29 90 increased + overcompensates 90 90 + 32 34 5 39 25 90 90 critical interval 40 transmural critical intervals 90 90 25 8 90 7 20 30 36 44 45 90 90 49 50 90 + o 90