Limits...
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

(a) Representative immunohistochemical staining of coronary arteries for DHE and vWF. Scale bar: 200 μm. (b–d) The ROS production, SOD activity, and MDA formation in HUVECs after incubation with 0.1% or 3% PolyPHb. One unit of SOD activity corresponded to 50% reduction of absorbance at 550 nm. Values are presented as mean ± SD (n = 5 to 6 per group). *P < 0.05 and **P < 0.01 versus the 0.1% PolyPHb group; #P < 0.05 and ##P < 0.01 versus the Control group. DHE: dihydroethidium; ROS: reactive oxygen species; SOD: superoxide dismutase; MDA: malonaldehyde; HUVECs: human umbilical vein endothelial cells.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4487275&req=5

fig6: (a) Representative immunohistochemical staining of coronary arteries for DHE and vWF. Scale bar: 200 μm. (b–d) The ROS production, SOD activity, and MDA formation in HUVECs after incubation with 0.1% or 3% PolyPHb. One unit of SOD activity corresponded to 50% reduction of absorbance at 550 nm. Values are presented as mean ± SD (n = 5 to 6 per group). *P < 0.05 and **P < 0.01 versus the 0.1% PolyPHb group; #P < 0.05 and ##P < 0.01 versus the Control group. DHE: dihydroethidium; ROS: reactive oxygen species; SOD: superoxide dismutase; MDA: malonaldehyde; HUVECs: human umbilical vein endothelial cells.

Mentions: An increase of positive staining of DHE was observed after coronary artery exposure to the 3% PolyPHb, indicating an overproduction of ROS in the coronary artery (Figure 6(a)). Also, the cell study confirmed that 3% PolyPHb treatment resulted in increased ROS production (P < 0.01 versus the 0.1% PolyPHb group; Figure 6(b)), inhibited SOD activity, and elevated MDA formation in HUVECs (P < 0.05 and P < 0.05 versus the 0.1% PolyPHb group; Figures 6(c) and 6(d)).


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)

(a) Representative immunohistochemical staining of coronary arteries for DHE and vWF. Scale bar: 200 μm. (b–d) The ROS production, SOD activity, and MDA formation in HUVECs after incubation with 0.1% or 3% PolyPHb. One unit of SOD activity corresponded to 50% reduction of absorbance at 550 nm. Values are presented as mean ± SD (n = 5 to 6 per group). *P < 0.05 and **P < 0.01 versus the 0.1% PolyPHb group; #P < 0.05 and ##P < 0.01 versus the Control group. DHE: dihydroethidium; ROS: reactive oxygen species; SOD: superoxide dismutase; MDA: malonaldehyde; HUVECs: human umbilical vein endothelial cells.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4487275&req=5

fig6: (a) Representative immunohistochemical staining of coronary arteries for DHE and vWF. Scale bar: 200 μm. (b–d) The ROS production, SOD activity, and MDA formation in HUVECs after incubation with 0.1% or 3% PolyPHb. One unit of SOD activity corresponded to 50% reduction of absorbance at 550 nm. Values are presented as mean ± SD (n = 5 to 6 per group). *P < 0.05 and **P < 0.01 versus the 0.1% PolyPHb group; #P < 0.05 and ##P < 0.01 versus the Control group. DHE: dihydroethidium; ROS: reactive oxygen species; SOD: superoxide dismutase; MDA: malonaldehyde; HUVECs: human umbilical vein endothelial cells.
Mentions: An increase of positive staining of DHE was observed after coronary artery exposure to the 3% PolyPHb, indicating an overproduction of ROS in the coronary artery (Figure 6(a)). Also, the cell study confirmed that 3% PolyPHb treatment resulted in increased ROS production (P < 0.01 versus the 0.1% PolyPHb group; Figure 6(b)), inhibited SOD activity, and elevated MDA formation in HUVECs (P < 0.05 and P < 0.05 versus the 0.1% PolyPHb group; Figures 6(c) and 6(d)).

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