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Treatment with the complement inhibitor, FUT‐175 decreases PMN activation and myocardial infarct size in Sprague‐Dawley rats
Author(s) -
Bonte Laura R La,
DavisGorman Grace,
Stahl Gregory L,
McDonagh Paul F
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.730.29
Subject(s) - medicine , complement system , reperfusion injury , ischemia , integrin alpha m , myocardial infarction , complement (music) , blood flow , inflammation , cardiology , pharmacology , immunology , chemistry , immune system , receptor , biochemistry , complementation , gene , phenotype
Complement activation plays an important role in the inflammatory response and is involved in ischemia/reperfusion (I/R) injury. The purpose of this study was to determine if the complement inhibitor, FUT175, attenuates neutrophil‐mediated myocardial I/R injury. Sprague‐Dawley (SD) rats underwent 30min of coronary artery occlusion followed by 120min of reperfusion. Treated SD rats were given FUT175 (1mg/kg) i.v. 5min prior to reperfusion. Left ventricular (LV) tissue samples were stained for complement deposition following reperfusion. We found that there was significantly increased complement deposition in the untreated SD LV compared to the FUT175 treated SD LV (43.9±6.1 %C3/LV vs. 14.7±6.0 %C3/LV, p<0.05). We also found that the infarct size of the FUT175 treated SD rats was significantly decreased (49.2±5.1 %AI/AAR vs. 21.1±4.8 %AI/AAR, p<0.01). Whole blood samples were taken pre‐ischemia, after 15min of reperfusion, and after 120min of reperfusion. Blood samples were processed for flow cytometric analysis of CD11b expression on activated PMNs at each time point. PMNs from the FUT175 treated rats exhibited significantly decreased CD11b expression compared to the untreated group (p<0.05). Taken together, these findings indicate a role for complement in the severity of I/R injury and that this injury can be attenuated with the complement inhibitor FUT175. Supported by NIH 58859 and AHA 0610018Z.