title: 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.affiliation: Department of Pulmonary Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.forename: L
authors.initials: L
authors.lastname: Zuo
mesh_terms: D000818:Animals; D002248:Carbon Monoxide; D005453:Fluorescence; D008297:Male; D051379:Mice; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D009211:Myoglobin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors
chemical_list: D009211:Myoglobin; C017595:oxymyoglobin; D013481:Superoxides; D002248:Carbon Monoxide