Characterization of oxygen radical formation mechanism at early cardiac ischemia.

Abstract

Myocardial ischemia-reperfusion (I/R) causes severe cardiac damage. Although the primary function of oxymyoglobin (Mb) has been considered to be cellular O2 storage and supply, previous research has suggested that Mb is a potentially protective element against I/R injury. However, the mechanism of its protective action is still largely unknown. With a real-time fluorescent technique, we observed that at the onset of ischemia, there was a small burst of superoxide (O2(•-)) release, as visualized in an isolated rat heart. Thus, we hypothesize that the formation of O2(•-) correlates to Mb due to a decrease in oxygen tension in the myocardium. Measurement of O2(•-) production in a Langendorff apparatus was performed using surface fluorometry. An increase in fluorescence was observed during the onset of ischemia in hearts perfused with a solution of hydroethidine, a fluorescent dye sensitive to intracellular O2(•-). The increase of fluorescence in the ischemic heart was abolished by a superoxide dismutase mimic, carbon monoxide, or by Mb-knockout gene technology. Furthermore, we identified that O2(•-) was not generated from the intracellular endothelium but from the myocytes, which are a rich source of Mb. These results suggest that during the onset of ischemia, Mb is responsible for generating O2(•-). This novel mechanism may shed light on the protective role of Mb in I/R injury.

• Authors: X Zhu, L Zuo
• Journal: Cell death & disease (Cell Death Dis) Vol. 4 Pg. e787 (Sep 05 2013) ISSN: 2041-4889 [Electronic] England
• PMID: 24008731 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Myoglobin
• oxymyoglobin
• Superoxides
• Carbon Monoxide

Topics

• Animals
• Carbon Monoxide
• Fluorescence
• Male
• Mice
• Myocardial Ischemia (metabolism, pathology)
• Myocardium (metabolism, pathology)
• Myoglobin (metabolism)
• Rats
• Rats, Sprague-Dawley
• Superoxides (metabolism)
• Time Factors