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Oxygen Sensing: Life and Death of a Cell
1Department of Emergency Medicine; 2Division of Pulmonary, Critical Care and Sleep Medicine, and 3Dorothy M. Davis Heart and Lung Research Institute, Ohio State University, Columbus, Ohio
Submitted 25 August 2006 ; accepted in final form 2 October 2006
Reperfusion of the ischemic myocardium leads to a burst of reactive O2 species (ROS), which is a primary determinant of postischemic myocardial dysfunction. We tested the hypothesis that early O2 delivery and the cellular redox state modulate the initial myocardial ROS production at reperfusion. Isolated buffer-perfused rat hearts were loaded with the fluorophores dihydrofluorescein or Amplex red to detect intracellular and extracellular ROS formation using surface fluorometry at the left ventricular wall. Hearts were made globally ischemic for 20 min and then reperfused with either 95% or 20% O2-saturated perfusate. The same protocol was repeated in hearts loaded with dihydrofluorescein and perfused with either 20 or 5 mM glucose-buffered solution to determine relative changes in NADH and FAD. Myocardial O2 delivery during the first 5 min of reperfusion was 84.7 ± 4.2 ml O2/min with 20% O2-saturated buffer and 354.4 ± 22.8 ml O2/min with 95% O2 (n = 8/group, P < 0.001). The fluorescein signal (intracellular ROS) was significantly increased in hearts reperfused with 95% O2 compared with 20% O2. However, the resorufin signal (extracellular ROS) was significantly increased with 20% O2 compared with 95% O2 during reperfusion. Perfusion of hearts with 20 mM glucose reduced the ·NADH during ischemia (P < 0.001) and the ·ROS at reperfusion (P < 0.001) compared with 5.5 mM-perfused glucose hearts. In conclusion, initial O2 delivery to the ischemic myocardium modulates a compartment-specific ROS response at reperfusion such that high O2 delivery promotes intracellular ROS and low O2 delivery promotes extracellular ROS. The redox state that develops during ischemia appears to be an important precursor for reperfusion ROS production.
ischemia; reoxygenation; oxygen radicals
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T. L. Clanton Hypoxia-induced reactive oxygen species formation in skeletal muscle J Appl Physiol, June 1, 2007; 102(6): 2379 - 2388. [Abstract] [Full Text] [PDF] |
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