Inhibition of Lipid Peroxidation During Cardiac Surgery
Status:
Completed
Trial end date:
2013-06-01
Target enrollment:
Participant gender:
Summary
Acute kidney injury is a major complication of cardiac surgery requiring cardiopulmonary
bypass (CPB). Hemolysis and rhabdomyolysis frequently occur during CPB. Hemolysis leads to an
increase in free hemoglobin, whereas rhabdomyolysis leads to an increase in myoglobin. Free
plasma hemoglobin and myoglobin have been shown to be independent predictors of the acute
kidney injury that results from CPB. When these hemeproteins are released into the plasma,
they undergo redox cycling, generating radical species that initiate lipid peroxidation and a
cascade of oxidative damage to cellular membranes, notably in the kidney. F2-isoprostanes and
isofurans are sensitive and specific markers of oxidative stress in vivo, and are increased
after CPB, particularly in those patients with acute kidney injury. Acetaminophen inhibits
the lipid peroxidation catalyzed by myoglobin and hemoglobin. Moreover, in an animal model of
rhabdomyolysis-induced kidney injury, acetaminophen significantly attenuated the decrease in
creatinine clearance compared to control. The current proposal tests the central hypothesis
that acetaminophen will attenuate the lipid peroxidation associated with the hemolysis and
rhabdomyolysis that occur in patients undergoing CPB. Demonstration that acetaminophen
inhibits the lipid peroxidation resulting from CPB would provide a rationale for a
prospective randomized trial to test the hypothesis that acetaminophen will reduce the acute
kidney injury that results from CPB.