We studied the effect of atrial pacing-induced myocardial ischemia on the generation of oxygen free radicals (OFR) in 8 patients with verified coronary artery disease (CAD) and in a control group of 4 patients without coronary atherosclerosis. Myocardial ischemia was measured metabolically by simultaneous lactate sampling from coronary sinus (CS) and arterial blood. Generation of OFR from purified viable polymorphonuclear neutrophils (PMN) was assessed by means of the chemiluminescence (CL) method. At peak pacing, 7 of 8 patients with CAD exhibited transient myocardial ischemia (mean lactate extraction ratio at rest: 23.6 +/- 7.7 vs 5.21 +/- 5.1% at peak pacing, p = 0.012). In these patients, unstimulated PMN harvested from the CS depicted a significant increase of luminol-enhanced CL (from 1.06 +/- 0.54 to 2.15 +/- 1.28 cpm x 10(5), p = 0.012) after atrial pacing. There was no additional effect from further ex vivo stimulation with phorbol myristate acetate. This finding underscores the role of myocardial ischemia as a potent endogenous activator of PMN function and may have implications in the pathogenesis and progression of atherosclerosis.