Inhibition of Lipid Peroxidation During Cardiac Surgery
| Status: | Not yet recruiting |
|---|---|
| Healthy: | No |
| Age Range: | 18 - 80 |
| Updated: | 5/27/2013 |
| Start Date: | July 2011 |
| End Date: | May 2016 |
| Contact: | Mias Pretorius, MBChB, MSCI |
| Email: | mias.pretorius@vanderbilt.edu |
| Phone: | 615-343-0665 |
Inhibition of Lipid Peroxidation During Cardiopulmonary Bypass
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.
Inclusion Criteria:
1. Subjects, 18 to 80 years of age, scheduled for elective cardiac surgery requiring CPB
2. For female subjects, the following conditions must be met:
postmenopausal for at least 1 year, or status-post surgical sterilization, or if of
childbearing potential, utilizing adequate birth control and a negative urine beta-hcg
prior to drug treatment
Exclusion Criteria:
1. Allergic reaction to ApAP (acetaminophen)
2. Evidence of severe hepatic impairment (history of liver cirrhosis or total bilirubin
>2.0mg/dl)
3. Impaired renal function (serum creatinine >2.0 mg/dl)
4. Emergency surgery
5. Pregnancy
6. Breast-feeding
7. Any underlying or acute disease requiring regular medication which could possibly
pose a threat to the subject or make implementation of the protocol or interpretation
of the study results difficult
8. History of alcohol or drug abuse
9. Treatment with any investigational drug in the 1 month preceding the study
10. Mental conditions rendering the subject unable to understand the nature, scope and
possible consequences of the study
11. Inability to comply with the protocol, e.g. uncooperative attitude and unlikelihood
of completing the study
12. History or evidence of active asthma
We found this trial at
1
site
1211 Medical Center Dr
Nashville, Tennessee 37232
Nashville, Tennessee 37232
(615) 322-5000
Vanderbilt Univ Med Ctr Vanderbilt University Medical Center (VUMC) is a comprehensive healthcare facility dedicated...
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