Creatine kinase-MB release during pacing-induced transient myocardial ischemia: Do oxygen free radicals mediate cardiac myocyte damage?

Background: The role of oxygen free radicals in transient episodes of myocardial ischemia is unknown. We, therefore, evaluated the in vivo activity of oxygen free radicals during pacing-induced myocardial ischemia and related it to malondialdehyde generation and creatine kinase-MB release. Method: Sixteen patients with coronary artery disease and chronic stable angina were studied. Atrial pacing rate was increased by 10 bpm every 3 minutes until myocardial ischemia or an atrioventricular Wenckebach period developed. Oxygen free radical activity, and malondialdehyde and creatine kinase-MB levels were measured at peak pacing rate and then 10 and 20 minutes after pacing was stopped. Results: Eight patients developed angina and ECG changes of myocardial ischemia, while another eight, with anatomically similar coronary artery disease, did not. Oxygen free-radical activity increased significantly only in patients who had inducible myocardial ischemia with atrial pacing. The high activity returned to normal within 20 minutes of resolution of ischemia. Malondialdehyde levels increased in the same group but remained elevated for up to 20 minutes. Creatine kinase-MB levels also increased only in this group but the rise in creatine kinase-MB was delayed and followed oxygen free-radical activation and malondialdehyde formation. These changes occurred in absence of any evidence of myocardial infarction. Conclusions: Transient myocardial ischemia induced by rapid atrial pacing can lead to oxygen free-radical generation, cardiac myocyte membrane damage, and release of creatine kinase-MB even in the absence of detectable myocardial infarction. It is possible that a similar process occurs in patients with coronary artery disease during spontaneous episodes of myocardial ischemia.