BackgroundAcute ischaemia and reperfusion (I-R) are associated with pro-arrhythmic electrophysiological changes such as action potential duration (APD) shortening and conduction velocity (CV) slowing, though data from human myocardium are sparse. We studied electrophysiological changes during I-R in intact human myocardium, comparing differences between failing and non-failing hearts. MethodsWe optically mapped coronary-perfused left ventricular wedge preparations from six human hearts with end-stage heart failure (HF) and six non-failing hearts from donors rejected for transplant (NF). At baseline, the preparations were subjected to steady-state pacing across a range of cycle lengths, and then subjected to 30 min of global ischaemia, followed by 30 min of reperfusion. Restitution pacing protocols were repeated after reperfusion. FindingsAt baseline, HF hearts had longer APD80 and slower transmural CV compared with NF hearts across a range of cycle lengths (both ANOVA p<0·001). APD80 and CV were reduced with ischaemia (at cycle lengths of 1000 ms, baseline vs 10 min ischaemia: mean HF APD 375 ms [SE 23] vs 324 [5], p<0·01; NF APD 308 [14] vs 271 [28], p<0·05; HF CV 29 cm/s [4] vs 16 [6], p<0·05; NF CV 40 [2] vs 23 [2], p<0·001), and were restored with reperfusion. APD shortening was greater in HF hearts during ischaemia (ΔAPD80 at 8 min ischaemia: mean HF 75 ms [SE 11], NF 25 [5]; p<0·01). Recovery of electrical excitability after reperfusion was delayed in HF (4·8 min [1·8] vs NF 1·0 [0], p<0.05). APD was restored to pre-ischaemic levels within the first minute of reperfusion in NF hearts, but restoration of APD was incomplete in HF early after reperfusion. InterpretationIn human myocardium, acute ischaemia was associated with APD shortening and CV slowing, which were reversed with reperfusion. In end-stage HF, these changes were accelerated during ischaemia, and recovery was slower following reperfusion. This may enhance the spatial gradients of repolarisation during acute I-R in failing hearts, and thus increase arrhythmia susceptibility. Further work is needed to elucidate the metabolic mechanisms underlying the adverse electrophysiological response to I-R in human heart failure. FundingNational Institute for Health Research, US National Institutes of Health, and British Heart Foundation.