INVESTIGATION OF THE MECHANISMS AND CONSEQUENCES OF TRANSIENT MYOCARDIAL ISCHAEMIA

A majority of patients with coronary artery disease do not suffer the morbidity and mortality of ischaemic heart disease. The basic mechanism for angina and myocardial infarction is probably myocardial ischaemia. The investigation of myocardial ischaemia represents an important goal for rational management and research. Patients with angina pectoris were admitted for the following investigations. Sixteen lead ECG maps with standardised exercise were performed to detect the precordial ischaemic ECG signs and exercise tolerance. Krypton-81m scientigraphy and pacing were used to study the sequence of changes in regional myocardial perfusion in relation to the ECG and pain during ischaemic events in patients. Ambulatory monitoring of the ECG and ST segment changes was used to identify evidence of ischaemia during the patients daily activities. The positron camera (11c-acetate and rubidium-82) was used with the electrocardiogram to examine regional myocardial perfusion and metabolism when the ST segment was isoelectric, depressed or elevated. Precordial mapping of the ECG revealed concentric regions on the chest with central regions of maximal ECG signs of ischaemia. Ambulatory monitoring of the electrocardiogram from this particular area identified more ischaemic events of which 52 % were asymptomatic. Ischaemic episodes occurred at night (21 %) and without any increase in the heart rate (20 %). Krypton scintigraphy showed that regional myocardial perfusion to segments of the ventricle supplied by stenosed coronary arteries increased, remain unchanged or decreased at the very onset of atrial pacing. Eventually during pacing, regional myocardial perfusion fell below the control values before the ECG and symptomatic evidence of myocardial ischaemia. There was a relationship between the amount of work performed during exercise and the pattern of disturbed regional myocardial perfusion. The positron camera demonstrated the transmural distribution of regional myocardial ischaemia in tomograms. Acute regional myocardial ischaemia was produced by cold, isometrics and exercise. The ischaemic lesion demonstrated an absolute reduction in the regional myocardial uptake of cation and this disturbance lasted for up to 40 minutes after the ECG and symptomatic evidence of ischaemia. The anaerobic metabolism affecting the ischaemic tissue was demonstrated by positive labelling with 11c-acetate. This also confirmed the prolonged metabolic derangement that followed an ischaemic event with angina. The standardised exercise test, ambulatory monitoring and positron camera were also used in clinical trials to show that the combined pharmacological effects of beta blockade and calcium antagonists were beneficial in the treatment of angina and myocardial ischaemia. Similarly a specific antagonist of platelet aggregation (Ticlopidine) showed a beneficial effect on episodes of myocardial ischaemia that occurred at night and without an increase in heart rate. These clinical trials indicate a possible role of platelets in the genesis of myocardial ischaemia in patients with coronary artery disease.