Ischemia-induced interleukin-8 release after human heart transplantation: A potential role for endothelial cells

Background: Interleukin-8 (IL-8) secreted from endothelial cells is a powerful neutrophil chemoattractant and activator. We hypothesized that human endothelial cells deprived of oxygen would secrete IL-8, which might translate into elevated IL-8 production after cardiac ischemia. Furthermore, we hypothesized that coronary sinus (CS) IL-8 levels would be particularly high after cardiac preservation for transplantation, due to extended ischemic times. Methods and Results: Human saphenous vein endothelial cells exposed to a hypoxic environment (PO₂ <20 mm Hg) demonstrated a time-dependent release of IL-8 (measured by ELISA) into the culture supernatant as early as 4 hours alter exposure. To determine whether cardiac preservation in humans was associated with IL-8 production, we obtained CS blood samples 5 minutes after reperfusion in a consecutive series of patients after they underwent cardiac transplantation (CTX, n=20) or elective cardiac surgery (non-CTX, n=21). CTX patients demonstrated significantly higher CS IL-8 levels than non-CTX patients (325±123 versus 50±17 ng/mL, respectively, P<.05). Further analysis of the CS samples revealed that a biochemical marker of myocyte injury (myoglobin) was similarly elevated in the CTX patients compared with the non-CTX patients (3340±625 versus 1151±525 ng/mL, respectively, P<.05). Conclusions: These differences may reflect the longer ischemic times of CTX compared with non-CTX hearts (161±10 versus 80±6 minutes, P<.0001) and suggest that the neutrophil chemoattractant/activator IL-8 may contribute to myocyte injury after prolonged hypothermic cardiac ischemia, as occurs during human cardiac transplantation.