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(Circulation. 1995;92:428-432.)
© 1995 American Heart Association, Inc.

Articles

Ischemia-Induced Interleukin-8 Release After Human Heart Transplantation

A Potential Role for Endothelial Cells

Mehmet C. Oz, MD; Hui Liao, MD; Yoshifuma Naka, MD; Alex Seldomridge, MD; David N. Becker; Robert E. Michler, MD; Craig R. Smith, MD; Eric A. Rose, MD; David M. Stern, MD; David J. Pinsky, MD

From the Departments of Surgery (M.C.O., Y.N., A.S., R.E.M., C.R.S., E.A.R.), Physiology (H.L., D.N.B., D.M.S.), and Medicine (D.J.P.), College of Physicians and Surgeons, Columbia University, New York, NY.

Correspondence to Mehmet C. Oz, MD, Columbia University, College of Physicians and Surgeons, Milstein 7-435, 177 Fort Washington Ave, New York, NY 10032. E-mail mco2@columbia.edu.

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 after 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.

Key Words: transplantation • ischemia • endothelium • interleukins

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