TY - JOUR
T1 - Hypoxic reperfusion of the ischemic heart and oxygen radical generation
AU - Angelos, Mark G.
AU - Kutala, Vijay K.
AU - Torres, Carlos A.
AU - He, Guanglong
AU - Stoner, Jason D.
AU - Mohammad, Marwan
AU - Kuppusamy, Periannan
PY - 2006/1
Y1 - 2006/1
N2 - Postischemic myocardial contractile dysfunction is in part mediated by the burst of reactive oxygen species (ROS), which occurs with the reintroduction of oxygen. We hypothesized that tissue oxygen tension modulates this ROS burst at reperfusion. After 20 min of global ischemia, isolated rat hearts were reperfused with temperature-controlled (37.4°C) Krebs-Henseleit buffer saturated with one of three different O 2 concentrations (95, 20, or 2%) for the first 5 min of reperfusion and then changed to 95% O 2. Additional hearts were loaded with 1) allopurinol (1 mM), a xanthine oxidase inhibitor, 2) diphenyleneiodonium (DPI; 1 γM), an NAD(P)H oxidase inhibitor, or 3) Tiron (10 mM), a superoxide scavenger, and were then reperfused with either 95 or 2% O 2 for the first 5 min. ROS production and tissue oxygen tension were quantitated using electron paramagnetic resonance spectroscopy. Tissue oxygen tension was significantly higher in the 95% O 2 group. However, the largest radical burst occurred in the 2% O 2 reperfusion group (P < 0.001). Recovery of left ventricular (LV) contractile function and aconitase activity during reperfusion were inversely related to the burst of radical production and were significantly higher in hearts initially reperfused with 95% O 2 (P < 0.001). Allopurinol, DPI, and Tiron reduced the burst of radical formation in the 2% O 2 reperfusion groups (P < 0.05). Hypoxic reperfusion generates an increased ROS burst originating from multiple pathways. Recovery of LV function during reperfusion is inversely related to this oxygen radical burst, highlighting the importance of myocardial oxygen tension during initial reperfusion.
AB - Postischemic myocardial contractile dysfunction is in part mediated by the burst of reactive oxygen species (ROS), which occurs with the reintroduction of oxygen. We hypothesized that tissue oxygen tension modulates this ROS burst at reperfusion. After 20 min of global ischemia, isolated rat hearts were reperfused with temperature-controlled (37.4°C) Krebs-Henseleit buffer saturated with one of three different O 2 concentrations (95, 20, or 2%) for the first 5 min of reperfusion and then changed to 95% O 2. Additional hearts were loaded with 1) allopurinol (1 mM), a xanthine oxidase inhibitor, 2) diphenyleneiodonium (DPI; 1 γM), an NAD(P)H oxidase inhibitor, or 3) Tiron (10 mM), a superoxide scavenger, and were then reperfused with either 95 or 2% O 2 for the first 5 min. ROS production and tissue oxygen tension were quantitated using electron paramagnetic resonance spectroscopy. Tissue oxygen tension was significantly higher in the 95% O 2 group. However, the largest radical burst occurred in the 2% O 2 reperfusion group (P < 0.001). Recovery of left ventricular (LV) contractile function and aconitase activity during reperfusion were inversely related to the burst of radical production and were significantly higher in hearts initially reperfused with 95% O 2 (P < 0.001). Allopurinol, DPI, and Tiron reduced the burst of radical formation in the 2% O 2 reperfusion groups (P < 0.05). Hypoxic reperfusion generates an increased ROS burst originating from multiple pathways. Recovery of LV function during reperfusion is inversely related to this oxygen radical burst, highlighting the importance of myocardial oxygen tension during initial reperfusion.
KW - Cardiac arrest
KW - Contractile function
KW - Reactive oxygen species
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U2 - 10.1152/ajpheart.00223.2005
DO - 10.1152/ajpheart.00223.2005
M3 - Article
C2 - 16126819
AN - SCOPUS:33644810433
SN - 0363-6135
VL - 290
SP - H341-H347
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 1
ER -