Excerpt
Hemorrhage is one of the main causes responsible for the impairment of blood flow, with subsequent tissue hypoperfusion and hypoxia. As the circulating blood volume decreases, oxygen consumption (
VO
2) remains constant for a considerable amount of blood loss. When the oxygen delivery (
DO
2) drops below a critical level, i.e. 10 mL O
2/min per kg,
VO
2 falls abruptly. This signifies a blood volume loss of approximately 50%, associated with substantial reduction in cardiac output and mixed venous oxygen saturation [
1]. At this stage of ischemia, deep tissue hypoxia leads the severely O
2-deprived cell to prime for generation of ROS, upon O
2 re-entry during reperfusion [
2]. Cellular priming consists of ATP depletion, since ATP degrades, reaching the level of hypoxanthine with concurrent xanthine oxidase accumulation. This situation is associated with either absolute O
2 2 restriction (no-flow state) or prolonged O
2 debt (low flow state) [
3]. The profuse and sudden oxygen re-entry at resuscitation acts as a cofactor, allowing xanthine oxidase to convert hypoxanthine to uric acid. The resulting by-products are superoxide anions (O
2 −) and hydrogen peroxide (H
2O
2), representing the main molecules of the initial oxidative burst [
2]. The aforementioned reactive oxygen species, along with the free radicals generated by NADPH oxidase within the neutrophils, attack peroxidating cell membranes. Consequently, ischemia/reperfusion injury occurs, the global equivalent of which is hemorrhagic shock and resuscitation. …
