Effect of repetitive episodes of exercise induced myocardial ischaemia on left ventricular function in patients with chronic stable angina: evidence for cumulative stunning or ischaemic preconditioning?

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Abstract
BACKGROUND Myocardial stunning is known to occur following a single episode of effort angina in patients with coronary artery disease. The effect on left ventricular (LV) function of repeated episodes of ischaemia is unknown. OBJECTIVES To investigate the effects of repeated episodes of exercise induced ischaemia on LV function in patients with chronic stable angina. METHODS Patients with significant coronary artery disease and normal LV function underwent two episodes of symptom limited treadmill exercise separated by three different time intervals: either 30 minutes (group A, n = 14); 60 minutes (group B, n = 14); or 240 minutes (group C, n = 14). Quantitative stress echocardiography was performed at repeated intervals between the two exercises and for 240 minutes following the second test. RESULTS For all groups there was no difference between the degree of ischaemia judged by maximal ST depression during the two tests. All episodes of exercise induced ischaemia produced prolonged abnormalities of LV systolic and diastolic function despite rapid normalisation of haemodynamic and ECG changes. In group A (30 minutes) these abnormalities were less pronounced after the second test than after the first, while in group B (60 minutes) they were more severe and long lasting. In group C (240 minutes) the two tests produced similar abnormalities of LV function. CONCLUSIONS Prolonged abnormalities of LV function occurred following exercise induced ischaemia with a time course consistent with myocardial stunning. The severity and degree of LV dysfunction caused by a further episode of ischaemia appear to be dependent on the time interval between ischaemic episodes.