Inhomogeneous transmural conduction during early ischaemia in patients with coronary artery disease

Abstract

Electrical inhomogeneity and conduction slowing are critical factors in the initiation and maintenance of ventricular arrhythmias during early ischaemia. Studies in animal models have shown delay in epicardial activation compared to endocardial activation. Epicardial activation delay has been attributed to either enhanced sensitivity of epicardium to ischaemia or to mid-myocardial conduction delay. No information is available in humans and in particular in patients with chronic ischaemia due to coronary artery disease who may have altered electrophysiological properties. Twenty-three patients undergoing routine coronary surgery were studied. All had severe two or three vessel coronary artery disease and a documented history of angina for a mean of 2.4 years. On cardiopulmonary bypass a 3 min period of ischaemia was created by cross clamping the aorta between the input from the pump oxygenator and the coronary arteries. During atrial pacing (normal endocardial to epicardial activation) intramyocardial activation time within the left ventricular free wall between subendocardial and subepicardial plunge electrode terminals, increased from 12.7+/-1.5 ms (control) to 28.2+/-3.2 ms after 3 min ischaemia at the base. At the apex, the activation time increase (over the same distance) was less (19.5+/-2 ms at 3 min ischaemia). This difference in increase in activation time at the base and apex was significant (P<0.05). At the apex the ischaemia induced activation delay occurred primarily over the endocardial half of the wall, whereas the opposite was observed at the base of the heart. Using an epicardial electrode array stimulation along the long axis of the epicardial fibres showed minimal conduction delay during ischaemia whereas stimulation transverse to the epicardial fibres resulted in substantial conduction time prolongation, as was the case with intramural conduction. Intramural conduction during ischaemia was similar in non-infarcted regions of infarcted hearts compared to hearts with no previous MI. To conclude, in patients with coronary artery disease epicardial activation delay early during ischaemia is caused primarily by intramural delay and not by delay along the epicardium. Moreover, the ischaemia-induced transmural activation delay is inhomogeneous.