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.


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.
Oz
M C
MC
Department of Surgery, College of Physicians and Surgeons, Columbia University, New York, NY 100032, USA.
Liao
H
H
Naka
Y
Y
Seldomridge
A
A
Becker
D N
DN
Michler
R E
RE
Smith
C R
CR
Rose
E A
EA
Stern
D M
DM
Pinsky
D J
DJ
D000368:Aged; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005260:Female; D016027:Heart Transplantation; D006801:Humans; D016209:Interleukin-8 / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood*; D011184:Postoperative Period; D012016:Reference Values; D012501:Saphenous Vein / Q000166:cytology / Q000502:physiology
D016209:Interleukin-8