Regional changes in ventricular excitability during load manipulation of the in situ pig heart.

1. The effect of load manipulation on myocardial excitability was studied in the anaesthetized, in situ pig heart. 2. A 33% increase in systolic left ventricular pressure achieved by aortic clamping reduced the mean effective refractory period by 11 ms (7.6%, P less than 0.01); whereas a 15% reduction in ventricular pressure achieved by intravenous infusion of sodium nitroprusside increased the mean effective refractory period by 4 ms (3.2%, P less than 0.05). 3. Changes in action potential duration, measured to 70% repolarization, roughly paralleled those of the effective refractory period. 4. The changes in effective refractory period were inhomogeneous, with a greater change occurring at the apex compared to the base in response to an increase in load, i.e. there was an increase in regional dispersion of refractoriness across the left ventricle. 5. Since inhomogeneity of repolarization and refractoriness is known to be potentially arrhythmogenic, these findings suggest that mechanical factors may contribute directly to the arrhythmias commonly seen clinically in high load states such as congestive cardiac failure and may also have consequences for the treatment of such arrhythmias.