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Steep action potential duration (APD) restitution has been shown to facilitate wavebreak and ventricular fibrillation. The global APD restitution properties in cardiac patients are unknown. We report a combined clinical electrophysiology and computer modelling study to: (1) determine global APD restitution properties in cardiac patients; and (2) examine the interaction of the observed APD restitution with known arrhythmia mechanisms. In 14 patients aged 52-85 years undergoing routine cardiac surgery, 256 electrode epicardial mapping was performed. Activation-recovery intervals (ARI; a surrogate for APD) were recorded over the entire ventricular surface. Mono-exponential restitution curves were constructed for each electrode site using a standard S1-S2 pacing protocol. The median maximum restitution slope was 0.91, with 27% of all electrode sites with slopes < 0.5, 29% between 0.5 and 1.0, and 20% between 1.0 and 1.5. Eleven per cent of restitution curves maintained slope > 1 over a range of diastolic intervals of at least 30 ms; and 0.3% for at least 50 ms. Activation-recovery interval restitution was spatially heterogeneous, showing regional organization with multiple discrete areas of steep and shallow slope. We used a simplified computer model of 2-D cardiac tissue to investigate how heterogeneous APD restitution can influence vulnerability to, and stability of re-entry. Our model showed that heterogeneity of restitution can act as a potent arrhythmogenic substrate, as well as influencing the stability of re-entrant arrhythmias. Global epicardial mapping in humans showed that APD restitution slopes were organized into regions of shallow and steep slopes. This heterogeneous organization of restitution may provide a substrate for arrhythmia.

Transmural repolarisation differences within the ventricular wall of the human heart were absent at cycle lengths within the physiological range but also during prolonged cycles. During early (global) ischaemia repolarisation changed equally in subepicardial and subendocardial regions and transmural homogeneity of repolarisation was preserved.

Aspirin has an established benefit in reducing the incidence of coronary events and vein graft occlusion. We have now assessed the risk of pre-operative aspirin in a prospective, randomised, double-blind clinical trial in 100 patients scheduled for elective coronary artery surgery. Any prescribed aspirin and non-steroidal anti-inflammatory drugs were discontinued 2 weeks pre-operatively and these were replaced by a randomly assigned tablet of either aspirin 300 mg daily or placebo taken until the day of surgery. Patient compliance was confirmed by serum and urinary salicylate analysis. The two groups were similar in demographic characteristics, bypass time, number of grafts placed and number of internal mammary arteries used. All patients survived to be discharged home (see Table). Aspirin decreases platelet aggregation to arachidonic acid and to collagen both pre- and post-operatively. The benefit of pre-operative aspirin has to be balanced against the risk of increasing post-operative blood loss, re-exploration for excessive bleeding and transfusion requirements.

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