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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

The net tension of coronary arteries (a) after incubation with 0.1% or 3% PolyPHb. SNP-induced endothelium-independent relaxation (b) and ACh-induced endothelium-dependent relaxation (c) in coronary arteries after incubation with 0.1% or 3% PolyPHb. Control vessels were treated with KH solution alone. Values are presented as mean ± SD (n = 5 to 6 per group). *P < 0.05 versus the 0.1% PolyPHb group; #P < 0.05 versus the Control group. SNP: sodium nitroprusside; Ach: acetylcholine; KH: Krebs-Henseleit.
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fig5: The net tension of coronary arteries (a) after incubation with 0.1% or 3% PolyPHb. SNP-induced endothelium-independent relaxation (b) and ACh-induced endothelium-dependent relaxation (c) in coronary arteries after incubation with 0.1% or 3% PolyPHb. Control vessels were treated with KH solution alone. Values are presented as mean ± SD (n = 5 to 6 per group). *P < 0.05 versus the 0.1% PolyPHb group; #P < 0.05 versus the Control group. SNP: sodium nitroprusside; Ach: acetylcholine; KH: Krebs-Henseleit.

Mentions: Incubation with the 0.1% PolyPHb did not alter the net tension of coronary artery, whereas it was greatly elevated by the 3% PolyPHb (0.29 ± 0.07 g; Figure 5(a)). Further study found that the endothelium-independent vasorelaxation induced by SNP did not differ among groups (Figure 5(b)). However, treatment with the 3% PolyPHb induced a significant impairment in vasodilatory responses to ACh (P < 0.05 versus the Sham group and P < 0.05 versus the 0.1% PolyPHb group; Figure 5(c)).


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)

The net tension of coronary arteries (a) after incubation with 0.1% or 3% PolyPHb. SNP-induced endothelium-independent relaxation (b) and ACh-induced endothelium-dependent relaxation (c) in coronary arteries after incubation with 0.1% or 3% PolyPHb. Control vessels were treated with KH solution alone. Values are presented as mean ± SD (n = 5 to 6 per group). *P < 0.05 versus the 0.1% PolyPHb group; #P < 0.05 versus the Control group. SNP: sodium nitroprusside; Ach: acetylcholine; KH: Krebs-Henseleit.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig5: The net tension of coronary arteries (a) after incubation with 0.1% or 3% PolyPHb. SNP-induced endothelium-independent relaxation (b) and ACh-induced endothelium-dependent relaxation (c) in coronary arteries after incubation with 0.1% or 3% PolyPHb. Control vessels were treated with KH solution alone. Values are presented as mean ± SD (n = 5 to 6 per group). *P < 0.05 versus the 0.1% PolyPHb group; #P < 0.05 versus the Control group. SNP: sodium nitroprusside; Ach: acetylcholine; KH: Krebs-Henseleit.
Mentions: Incubation with the 0.1% PolyPHb did not alter the net tension of coronary artery, whereas it was greatly elevated by the 3% PolyPHb (0.29 ± 0.07 g; Figure 5(a)). Further study found that the endothelium-independent vasorelaxation induced by SNP did not differ among groups (Figure 5(b)). However, treatment with the 3% PolyPHb induced a significant impairment in vasodilatory responses to ACh (P < 0.05 versus the Sham group and P < 0.05 versus the 0.1% PolyPHb group; Figure 5(c)).

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