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

Abstract

Background: 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. Methods: 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 μl ± 27 μl) 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. Results: Relative expression of intercellular adhesion molecule-1, vascular adhesion molecule-1, interleukin-1β, and interleukin-6 mRNAs differed significantly (2.4 –4.6 times higher) between brain-dead and control hearts ( p < 0.05; group t-test). Conclusion: Increases in the inflammatory cytokine, interleukin-1β, 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.