Use of iron chelators in cardiac surgery with cardiopulmonary bypass.

Abstract

The cardiopulmonary bypass (CPB) exposes blood to non-physiological surfaces and shear forces that lead to the mechanical destruction of red blood cells with the release of free hemoglobin in the circulation. In the presence of oxidants such as hydrogen peroxide and superoxide, free iron is released from heme molecules into the circulation. Iron is a transition metal that has the ability to donate or accept individual electrons. This allows iron to neutralize free radicals and therefore serves as a critical antioxidant defense. In order to maintain the physiological oxidative state of the cells, iron is sequestered with proteins or cofactors. Iron chelators form a complex with iron and, therefore, promote its excretion through the urinary or bile ducts. In several experimental FRA models, the pretreatment of chelation of iron and deferoxamine protects animals against a wide range of nephrotoxic insults. In conclusion, more studies are needed to determine if plasma catalytic iron can serve as a useful biomarker of ARI in humans. In addition, clinical trials with adequate power are needed to assess whether interventions targeting iron regulatory pathways can improve clinical outcomes in human ARI. Current treatment of ARF remains largely favorable. However, recent advances in our understanding of kidney injury and repair signaling pathways in preclinical models have allowed the development of several promising pharmaceutical products that are currently in clinical trials in humans.