Selective overexpression of inflammatory molecules in hearts from brain-dead rats

Inflammatory processes that occur before, during, and after surgery may contribute to damage of transplanted hearts and their ability to withstand acute and chronic rejection.

We determined the expression of mRNA for 10 inflammatory indicator molecules in hearts from brain-dead animals in which stable circulation was maintained. To produce brain death in male rats (n = 11), we inflated an intracranial balloon with saline (245 microl +/- 27 microl) to produce apnea and areflexia. Mean arterial pressure was maintained at 80 +/- 2 mm Hg for 6 hours. Controls (n = 11) received a burr hole but no balloon (mean arterial pressure, 94 +/- 1 mm Hg). We measured expression of each indicator molecule mRNA relative to expression of glyceraldehyde-3-phosphate dehydrogenase mRNA using reverse-transcriptase polymerase chain reaction.

Relative expression of intercellular adhesion molecule-1, vascular adhesion molecule-1, interleukin-1beta, and interleukin-6 mRNAs differed significantly (2.4 -4.6 times higher) between brain-dead and control hearts (p < 0.05; group t-test).

Increases in the inflammatory cytokine, interleukin-1beta, whose mRNA also increased, may mediate the overexpression of the adhesion molecule and interleukin-6 mRNAs. The data suggest that endothelial cells become inflamed during brain death, even when the circulation is stable, which may lead to leukocyte-endothelial interactions during brain death or after graft transplantation.