Soluble L-selectin and neutrophil derived oxidative stress after pacing induced myocardial ischemia in chronic stable coronary artery disease

We studied the effect of atrial pacing induced myocardial ischemia on levels of soluble L-selectin (sL-selectin) and generation of neutrophil derived reactive oxygen species (ROS) in 10 patients with coronary artery disease (CAD) and stable angina and in six individuals without CAD. Myocardial ischemia was measured metabolically by lactate sampling from the coronary sinus (CS) and arterial blood at each pacing step. Before each pacing step, at peak pacing and shortly after cessation, plasma concentrations of sL-selectin and generation of ROS using the chemiluminescence method were measured in CS and femoral artery blood. Baseline sL-selectin levels in CS samples were significantly lower in the CAD compared to the control group (547 ± 80 vs 836 ± 82 ng/mL, P = 0.03). At peak pacing, nine often patients with CAD developed myocardial ischemia (lactate extraction ratio at rest 28% ± 7%, at peak pacing -16% ± 6%). In these patients, luminol-enhanced chemiluminescence (CL, 0.88 ± 0.45 vs 1.9 ± 0.9 cpm x 10⁵, P = 0.09) and levels of sL-selectin (547 ± 80 vs 764 ± 86 ng/mL, P = 0.03) from naive neutrophils increased significantly in CS blood suggesting a potent in vivo activation of neutrophils. In control patients, incremental pacing caused neither myocardial ischemia nor a significant change of chemiluminescence or of sL-selectin levels. In conclusion, myocardial ischemia induced by pacing tachycardia is able to activate neutrophils in patients with chronic stable coronary artery disease leading to increased generation of ROS and shedding of L-selectin into the coronary circulation.