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High-Dose Polymerized Hemoglobin Fails to Alleviate Cardiac Ischemia/Reperfusion Injury due to Induction of Oxidative Damage in Coronary Artery.

Yang Q, Wu W, Li Q, Chen C, Zhou R, Qiu Y, Luo M, Tan Z, Li S, Chen G, Zhou W, Liu J, Yang C, Liu J, Li T - Oxid Med Cell Longev (2015)

Bottom Line: 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.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, China ; Department of Medicinal Chemistry, School of Pharmacy, Chengdu Medical College, Chengdu 610083, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Total CK-MB (a), LDH (b), and cTnI (c) releases at baseline and after 2-hour reperfusion (n = 6). (d) Representative photomicrographs of H&E-stained left ventricular tissue section (n = 5). Scale bar: 100 μm. (e) Pathological scores for hyaline change, cloudy swelling, fatty change, inflammatory infiltration, perinuclear halo, interstitial edema, and acute myocardial necrosis. Values are presented as mean ± SD. *P < 0.05, **P < 0.01, and ***P < 0.001 versus the 0.1% PolyPHb group; #P < 0.05 versus the I/R group. CK-MB: creatine kinase-MB; LDH: lactate dehydrogenase; cTnI: cardiac troponin-I; H&E: hematoxylin and eosin.
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fig4: Total CK-MB (a), LDH (b), and cTnI (c) releases at baseline and after 2-hour reperfusion (n = 6). (d) Representative photomicrographs of H&E-stained left ventricular tissue section (n = 5). Scale bar: 100 μm. (e) Pathological scores for hyaline change, cloudy swelling, fatty change, inflammatory infiltration, perinuclear halo, interstitial edema, and acute myocardial necrosis. Values are presented as mean ± SD. *P < 0.05, **P < 0.01, and ***P < 0.001 versus the 0.1% PolyPHb group; #P < 0.05 versus the I/R group. CK-MB: creatine kinase-MB; LDH: lactate dehydrogenase; cTnI: cardiac troponin-I; H&E: hematoxylin and eosin.

Mentions: As markers of myocardial necrosis, the levels of CK-MB, LDH, and cTnI in plasma were greatly increased in the I/R group. Less cardiac enzymes release was observed in the 0.1% PolyPHb group, whereas in the 3% PolyPHb group, the enzymes release was still in a high level and not different from the I/R group (Figures 4(a)–4(c)). Moreover, the results of H&E staining showed that the 3% PolyPHb did not limit myocardial histopathological changes after I/R injury and further increased myocardial necrosis (P < 0.05 versus the I/R group; Figures 4(d) and 4(e)).


High-Dose Polymerized Hemoglobin Fails to Alleviate Cardiac Ischemia/Reperfusion Injury due to Induction of Oxidative Damage in Coronary Artery.

Yang Q, Wu W, Li Q, Chen C, Zhou R, Qiu Y, Luo M, Tan Z, Li S, Chen G, Zhou W, Liu J, Yang C, Liu J, Li T - Oxid Med Cell Longev (2015)

Total CK-MB (a), LDH (b), and cTnI (c) releases at baseline and after 2-hour reperfusion (n = 6). (d) Representative photomicrographs of H&E-stained left ventricular tissue section (n = 5). Scale bar: 100 μm. (e) Pathological scores for hyaline change, cloudy swelling, fatty change, inflammatory infiltration, perinuclear halo, interstitial edema, and acute myocardial necrosis. Values are presented as mean ± SD. *P < 0.05, **P < 0.01, and ***P < 0.001 versus the 0.1% PolyPHb group; #P < 0.05 versus the I/R group. CK-MB: creatine kinase-MB; LDH: lactate dehydrogenase; cTnI: cardiac troponin-I; H&E: hematoxylin and eosin.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4487275&req=5

fig4: Total CK-MB (a), LDH (b), and cTnI (c) releases at baseline and after 2-hour reperfusion (n = 6). (d) Representative photomicrographs of H&E-stained left ventricular tissue section (n = 5). Scale bar: 100 μm. (e) Pathological scores for hyaline change, cloudy swelling, fatty change, inflammatory infiltration, perinuclear halo, interstitial edema, and acute myocardial necrosis. Values are presented as mean ± SD. *P < 0.05, **P < 0.01, and ***P < 0.001 versus the 0.1% PolyPHb group; #P < 0.05 versus the I/R group. CK-MB: creatine kinase-MB; LDH: lactate dehydrogenase; cTnI: cardiac troponin-I; H&E: hematoxylin and eosin.
Mentions: As markers of myocardial necrosis, the levels of CK-MB, LDH, and cTnI in plasma were greatly increased in the I/R group. Less cardiac enzymes release was observed in the 0.1% PolyPHb group, whereas in the 3% PolyPHb group, the enzymes release was still in a high level and not different from the I/R group (Figures 4(a)–4(c)). Moreover, the results of H&E staining showed that the 3% PolyPHb did not limit myocardial histopathological changes after I/R injury and further increased myocardial necrosis (P < 0.05 versus the I/R group; Figures 4(d) and 4(e)).

Bottom Line: 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.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu 610041, China ; Department of Medicinal Chemistry, School of Pharmacy, Chengdu Medical College, Chengdu 610083, China.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus