The development of shock can progress into circulatory collapse, which is a catastrophic complication of trauma. Amongst the complex changes arising during the development of shock is the emergence of the “heat shock proteins.” Heat shock protein 32 is also known as the inducible heme oxygenase (HO)-1. This ubiquitous enzyme catalyzes the metabolism of heme to generate carbon monoxide (CO) in an O2-dependent reaction. In fact, this endogenous source of CO has recently been implicated in the promotion of smooth muscle relaxation, endothelial impairment and cardiac contractility failure. Traumatic blood loss can promote the generation of inflammatory cytokines such as interleukin (IL)-6 and tissue necrosis factor (TNF)-α; both are potent inducers HO-1. The current study was designed to determine if hemorrhagic loss enhances the formation inflammatory cytokines, which in turn promote an induction of HO-1 to result in pathological elevations in CO formation. For this purpose, male Sprague-Dawley rats (300-325 g) were implanted with chronic indwelling carotid catheters. Following 4 days recovery, cytokine and HO-1 expression were measured 24 hours after exposure to a 9 mL blood loss, and were contrasted to unbled controls. Hemorrhagic shock increased HO-1 protein content (ELISA method) 1.8-fold in abdominal aorta tissues (1.6 ± 0.8 vs 2.8 ± 0.4 ng HO-1/mg protein, p < .05). There were no differences in plasma IL-6 and TNF-α levels in animals 24 hours after hemorrhage, relative to the non-bled controls. Total hemoglobin and O2 content were decreased in bled animals (tHb-control: 8.8 ± 0.1 mM vs. bled: 4.2 ± 0.3 mM, O2ct-control: 18.5 ± 0.5 vs. bled: 8.7 ± 0.6; p < .05 each) while blood lactate levels were only slightly elevated relative to non-bled controls. These data show that controlled blood loss can decrease endogenous production of CO but is followed by an induction of HO-1 that is associated with the restoration of CO levels. In addition, it shows that hemorrhagic loss can promote the induction of HO-1 in a manner which is independent of altered expression of inflammatory cytokines. The findings suggest that endogenous CO production is dependent both upon circulating levels of O2 and the expression of HO-1 but does not require the expression of inflammatory cytokines.
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