Biphasic elevation of bilirubin oxidation during myocardial ischemia reperfusion.
BACKGROUND
The time course of oxidative stress involving nitric oxide (NO) after myocardial ischemia reperfusion (MIR) has not been elucidated in detail, so the present study was designed to assess the dynamics of oxidative stress after MIR, urinary excretion of oxidized bilirubin metabolites (ie, biopyrrins) and their generation in various organs.


RESULTS
Rat models of MIR were created by occluding the left coronary artery for 30 min followed by 48 h of reperfusion. Levels of urinary biopyrrins increased biphasically at 8 h and 24 h after MIR. Biopyrrins were upregulated in the lungs at 8 h after MIR, according to immunohistochemistry and ELISA, and at 24 h biopyrrin expression was increased in the heart and lungs. The NO synthase inhibitor, NG-monomethyl-L-arginine, significantly diminished biopyrrin synthesis in the heart and lungs at 24 h, but not in the lungs at 8 h after MIR. Hemodynamic assessment revealed increased left ventricle end-diastolic pressure, suggesting that lung congestion influences pulmonary biopyrrin formation.


CONCLUSIONS
The dynamics of urinary biopyrrins might reflect earlier biopyrrin generation in the lungs and delayed formation in both the lungs and heart when NO is involved. Therefore, urinary biopyrrins can serve as a useful marker of systemic oxidative stress after MIR.
Yamamoto
Masaki
M
Department of Surgery II, Faculty of Medicine, Kochi University, Nankoku, Japan.
Maeda
Hironori
H
Hirose
Nobuyuki
N
Yamamoto
Morio
M
Nakagawa
Aimi
A
Radhakrishnan
Geethalakshmi
G
Gopalrao
Rajesh Katare
RK
Sato
Takayuki
T
Yamaguchi
Tokio
T
Sasaguri
Shiro
S
D000818:Animals; D001663:Bilirubin / Q000652:urine*; D015415:Biomarkers / Q000652:urine; D004177:Dipyrone / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D013997:Time Factors
D015415:Biomarkers; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D004177:Dipyrone; D001663:Bilirubin; D019331:NG-Nitroarginine Methyl Ester