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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 HR (a), MAP (b), CVP (c), PAWP (d), PAP (e), LVSP (f), LVEDP (g), and CO (h) at baseline and during 2-hour of reperfusion (n = 5). Values are presented as mean ± SD. *P < 0.05 and **P < 0.01 versus the 0.1% group; #P < 0.05 versus the I/R group. HR: heart rate; MAP: mean arterial pressure; CVP: central venous pressure; PAWP: pulmonary artery wedge pressure; PAP: pulmonary arterial pressure; LVSP: left ventricular systolic pressure; LVEDP: left ventricular end-diastolic pressure; CO: cardiac output.
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fig2: The HR (a), MAP (b), CVP (c), PAWP (d), PAP (e), LVSP (f), LVEDP (g), and CO (h) at baseline and during 2-hour of reperfusion (n = 5). Values are presented as mean ± SD. *P < 0.05 and **P < 0.01 versus the 0.1% group; #P < 0.05 versus the I/R group. HR: heart rate; MAP: mean arterial pressure; CVP: central venous pressure; PAWP: pulmonary artery wedge pressure; PAP: pulmonary arterial pressure; LVSP: left ventricular systolic pressure; LVEDP: left ventricular end-diastolic pressure; CO: cardiac output.

Mentions: All the hemodynamic parameters at baseline, as well as the HR, CVP, and MAP during reperfusion, were not different among groups (Figures 2(a)–2(c)). Treatment with the low-dose PolyPHb exhibited cardioprotective effect. Increase of the dosage of PolyPHb did not enhance this effect, as shown by the increased PAWP, PAP, and LVEDP and reduced LVSP and CO (all P < 0.001 versus the Sham group; Figures 2(d)–2(h)). The recovery of LVEDP and CO during the first 60 minutes of reperfusion were even worse as compared to the I/R group (P < 0.05 and P < 0.05, respectively; Figures 2(g) and 2(h)). In addition, the 0.1% PolyPHb alleviated the reduction of cardiac VO2 and elevated O2EI as compared to the I/R group, while the 3% PolyPHb failed to improve these parameters and further decreased cardiac VO2 at 60 minutes of reperfusion (P < 0.05 versus the I/R group; Figure 3).


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 HR (a), MAP (b), CVP (c), PAWP (d), PAP (e), LVSP (f), LVEDP (g), and CO (h) at baseline and during 2-hour of reperfusion (n = 5). Values are presented as mean ± SD. *P < 0.05 and **P < 0.01 versus the 0.1% group; #P < 0.05 versus the I/R group. HR: heart rate; MAP: mean arterial pressure; CVP: central venous pressure; PAWP: pulmonary artery wedge pressure; PAP: pulmonary arterial pressure; LVSP: left ventricular systolic pressure; LVEDP: left ventricular end-diastolic pressure; CO: cardiac output.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: The HR (a), MAP (b), CVP (c), PAWP (d), PAP (e), LVSP (f), LVEDP (g), and CO (h) at baseline and during 2-hour of reperfusion (n = 5). Values are presented as mean ± SD. *P < 0.05 and **P < 0.01 versus the 0.1% group; #P < 0.05 versus the I/R group. HR: heart rate; MAP: mean arterial pressure; CVP: central venous pressure; PAWP: pulmonary artery wedge pressure; PAP: pulmonary arterial pressure; LVSP: left ventricular systolic pressure; LVEDP: left ventricular end-diastolic pressure; CO: cardiac output.
Mentions: All the hemodynamic parameters at baseline, as well as the HR, CVP, and MAP during reperfusion, were not different among groups (Figures 2(a)–2(c)). Treatment with the low-dose PolyPHb exhibited cardioprotective effect. Increase of the dosage of PolyPHb did not enhance this effect, as shown by the increased PAWP, PAP, and LVEDP and reduced LVSP and CO (all P < 0.001 versus the Sham group; Figures 2(d)–2(h)). The recovery of LVEDP and CO during the first 60 minutes of reperfusion were even worse as compared to the I/R group (P < 0.05 and P < 0.05, respectively; Figures 2(g) and 2(h)). In addition, the 0.1% PolyPHb alleviated the reduction of cardiac VO2 and elevated O2EI as compared to the I/R group, while the 3% PolyPHb failed to improve these parameters and further decreased cardiac VO2 at 60 minutes of reperfusion (P < 0.05 versus the I/R group; Figure 3).

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