Heme-Oxygenase-1 mRNA Expression Affects Hemorrhagic Shock-Induced Leukocyte Adherence

BACKGROUND Hemorrhagic shock-related leukocyte adherence to endothelial cells is a key step in microvascular injury-related organ damage. Heme-oxygenase-1 (HO-1) metabolizes heme, a potent cytotoxic agent, to carbon monoxide and biliverdin. We hypothesized that changing HO-1 expression would change leukocyte adherence after hemorrhagic shock. METHODS Rats were administered hemin, zinc protoporphyrin, or vehicle 6 hours before surgery. HO-1 expression was determined by reverse-transcriptase polymerase chain reaction in various tissues. Shock was induced in urethane-anesthetized animals by decreasing mean arterial blood pressure to 40 mm Hg for 60 minutes, followed by standard resuscitation measures. Leukocyte adherence was measured by intravital microscopy in rat mesenteric venules. RESULTS Hemin, hemorrhagic shock, and the combination resulted in significantly increased HO-1 expression, whereas zinc-protoporphyrin (ZNPP) resulted in significantly decreased leukocyte adherence. After hemorrhagic shock and hemin administration, leukocyte adherence was significantly decreased 60 minutes into resuscitation (7.92 +/- 2.29 vs. 4.84 +/- 0.71 cells/100 microm, p < 0.05) and significantly increased after ZNPP plus shock (14.08 +/- 3.95, p