Journal
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
Volume 2015, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2015/125106
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Funding
- National Natural Science Foundation of China [81100180, 81471042]
- Research Fund for Outstanding Young Scholars of Sichuan University
- National High Technology Research and Development Program of China (863 Program) [2012AA021903]
- Science and Technology Support Program of Sichuan Province [2013SZ0059]
- Special Foundation for Technology Innovation Program of Sichuan Province [2013ZZ0006]
- Research Funds in Chengdu Military Hospital [2011YG-B08, 2013YG-B028]
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Objective. Ischemia/reperfusion (I/R) injury is an unavoidable event for patients in cardiac surgery under cardiopulmonary bypass (CPB). This study was designed to investigate whether glutaraldehyde-polymerized human placenta hemoglobin (PolyPHb), a hemoglobin-based oxygen carrier (HBOC), can protect heart against CPB-induced I/R injury or not and to elucidate the underlying mechanism. Methods and Results. A standard dog CPB model with 2-hour cardiac arrest and 2-hour reperfusion was established. The results demonstrated that a low-dose PolyPHb (0.1%, w/v) provided a significant protection on the I/R heart, whereas the high-dose PolyPHb (3%, w/v) did not exhibit cardioprotective effect, as evidenced by the impaired cardiac function, decreased myocardial oxygen utilization, and elevated enzymes release and pathological changes. Further study indicated that exposure of isolated coronary arteries or human umbilical vein endothelial cells (HUVECs) to a high-dose PolyPHb caused impaired endothelium-dependent relaxation, which was companied with increased reactive oxygen species (ROS) production, reduced superoxide dismutase (SOD) activity, and elevated malonaldehyde(MDA) formation. Consistent with the increased oxidative stress, the NAD(P)H oxidase activity and subunits expression, including gp91(phox), p47(phox), p67(phox), and Nox1, were greatly upregulated. Conclusion. The high-dose PolyPHb fails to protect heart from CPB-induced I/R injury, which was due to overproduction of NAD(P)H oxidase-induced ROS and resultant endothelial dysfunction.
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