Biphasic Elevation of Bilirubin Oxidation During Myocardial Ischemia Reperfusion

Abstract

lthough therapeutic intervention or coronary artery bypass grafting can recover coronary blood flow, myocardial damage after blood flow reperfusion, namely myocardial ischemia reperfusion (MIR) injury, remains to be resolved. Among the factors affecting MIR, oxidative stress might play an important role in both the myocardial injury and the cardiac events after reperfusion therapy. 1 Oxidative stress induced by superoxide generated via the xanthine oxidase system and infiltrating inflammatory cells is the major proposed mechanism of MIR progression. [2][3][4][5] We have reported that reactive oxygen species (ROS) influence the opening of the mitochondrial permeability transition pore in myocardial cells, which led to progression of myocardial infarction (MI) in a rat MIR model. 6 Moreover, total nitric oxide (NO) synthesis in the reperfused heart was increased in previous investigations. 7-9 Physiological concentrations of NO produced from endothelial NO synthase (eNOS) or NO donors exert significant cardioprotective effects, whereas the reaction between NO and ROS produces peroxynitrite and results in oxidative and nitrative tissue injury. [7][8][9][10][11][12][13] Evidence from several model systems supports the notion that NO radicals cause myocardial damage in MIR, 7,8,[12][13][14][15] whereas a small amount of NO exerts a cytoprotective effect in the reperfused heart. 11,12,16,17 The dynamics of oxidative stress up to 48 h after MIR remain unclear because of the difficulties associated with monitoring oxidation in vivo. This period is considered critical in both cardiac surgery and therapeutic intervention, so more sensitive and reliable markers of in vivo oxidative stress are required.Bilirubin is an intrinsic antioxidant that quenches radicals under several inflammatory conditions. 18-21 Its synthesis is regulated by the rate-limiting enzyme, heme oxygenase-1 (HO-1), which is rapidly induced by oxidative stress and inflammatory reactions caused by factors such as cytokines, ischemia and NO. [22][23][24][25][26][27][28][29] Bilirubin generates several hydrophilic metabolites called biopyrrins upon oxidation and these can be detected using the anti-bilirubin monoclonal antibody 24G7. 30,31 Biopyrrins are immediately excreted in urine because of their hydrophilic properties and thus can reflect the severity of oxidative stress. 25,[32][33][34][35][36][37][38] Biopyrrin synthesis reflects NO radicals, 25 so urinary biopyrrin levels can indicate ongoing changes in oxidative stress in vivo and thus function as a marker of oxidative stress.The time course of urinary and tissue biopyrrin levels in rat models of cardiac transplantation and hepatic ischemia reperfusion has been investigated. 25,32 A cardiac transplantation study showed that levels of urinary biopyrrins become more rapidly and sensitively elevated than either urinary 8-hydroxy-2'-deoxyguanosine or serum troponin-T during Biphasic Elevation of Bilirubin Oxidation During Myocardial Ischemia ReperfusionMasaki Yamamoto, MD; Hironori Maeda, MD; Nobuyuki...

Change in Ischemia-Modified Albumin and Its Clinical Significance During Exercise Stress Testing

“…[17][18][19][20] In this study, we demonstrated that an increase in IMA after EST suggests a large ischemic burden of CAD.…”

Bilirubin Is Negatively Associated With Hemoglobin A1c Independently of Other Cardiovascular Risk Factors in Apparently Healthy Japanese Men and Women

“…19 Yamamoto et al studied the dynamics of oxidative stress after myocardial ischemia reperfusion in rat models using urinary excretion of biopyrrins and their generation in various organs as oxidative stress markers and suggested that urinary excretion of biopyrrins can serve as a useful marker of systemic oxidative stress after myocardial ischemia -reperfusion. 20 Ueyama et al reported that cardiac and aortic macrophages upregulate HO-1 in response to emotional stress and catecholamine surges as an endogenous defense mechanism against oxidative stress in rat models of takotsubo cardiomyopathy. 21 Kunii et al demonstrated that serum bilirubin and biopyrrins were elevated in patients with acute myocardial infarction, and that biopyrrins and HO-1 expression were increased in the infarcted myocardium and that plasma and urinary biopyrrin elevation was associated with mortality and morbidity.…”

Dynamics of Oxidative Stress Evoked by Myocardial Ischemia Reperfusion After Off-Pump Coronary Artery Bypass Grafting Elucidated by Bilirubin Oxidation

“…the alveolar wall in the lungs after MIR, as in systemic inflammatory response syndrome (SIRS). 13 However, further study is required to elucidate the relationship between lung congestion and oxidative stress, as the lung is a target in various inflammatory situations and because the mechanism by which oxidative stress is generated in the lung is not well understood. 32 There was no significant difference between the UAP and EAP groups statistically, as this study had a small sample size.…”