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Carbon monoxide inhibits myocardial oxygen free radical generation following the onset of ischemia
Author(s) -
Zuo Li,
Talukder M.A. Hassan,
Palmer Brian,
Clanton Thomas L.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.747.12
Subject(s) - ischemia , superoxide , chemistry , oxygen , heme , carbon monoxide , superoxide dismutase , medicine , ventricle , cardiology , biochemistry , oxidative stress , enzyme , organic chemistry , catalysis
Reperfusion of the ischemic heart causes a burst of oxygen free radical (OFR) formation and secondary myocardial damage. However, questions remain on the mechanisms of OFR generation during ischemia. Recently, it has been reported that superoxide can derive from heme‐protein oxidation immediately following the onset of ischemia. Therefore, we tested the hypothesis that if OFR generation following ischemia involves heme‐protein oxidation then it should be inhibited by carbon monoxide (CO). Surface fluorometry was used to measure OFR generation during the onset of global ischemia in isolated rat heart. The fiber optic probe facing the left ventricle (LV) obtained the fluorescence signal from the heart. Hydroethidine (HE) was used as a sensitive probe to measure superoxide. When exposed to superoxide, HE is converted to ethidium (ET). Hearts were perfused with 44μM HE for 1.5 −5 min. We observed a rapid increase in ET signal with the onset of ischemia and that reached to a peak within 5 min. ET signal was completed blocked by a SOD mimic, MnPyP (250μM, P<0.01). Importantly, CO (100μM) treatment significantly reduced ET signal to 30% of control (P<0.01). Thus, there is a burst of OFR generation during the onset of myocardial ischemia in isolated rat heart. We report for the first time that CO inhibits OFR generation during myocardial ischemia, indicating that heme‐protein oxidation plays a crucial role in OFR generation.