The effects of the fibrin-derived peptide Bbeta(15-42) in acute and chronic rodent models of myocardial ischemia-reperfusion.
Many compounds have been shown to prevent reperfusion injury in various animal models, although to date, translation into clinic has revealed several obstacles. Therefore, the National Heart, Lung, and Blood Institute convened a working group to discuss reasons for such failure. As a result, the concept of adequately powered, blinded, randomized studies for preclinical development of a compound has been urged. We investigated the effects of a fibrin-derived peptide Bbeta(15-42) in acute and chronic rodent models of ischemia-reperfusion at three different study centers (Universities of Dusseldorf and Vienna, TNO Biomedical Research). A total of 187 animals were used, and the peptide was compared with the free radical scavenger Tempol, CD18 antibody, alpha-C5 antibody, and the golden standard, ischemic preconditioning. We show that Bbeta(15-42) robustly and reproducibly reduced infarct size in all models of ischemia-reperfusion. Moreover, the peptide significantly reduced plasma levels of the cytokines interleukin 1beta, tumor necrosis factor alpha, and interleukin 6. In rodents, Bbeta(15-42) inhibits proinflammatory cytokine release and is cardioprotective during ischemia-reperfusion injury.
Zacharowski
Kai
K
Molecular Cardioprotection & Inflammation Group, Department of Anesthesia, University Hospital of Dusseldorf, Dusseldorf, Germany. kai.zacharowski@bristol.ac.uk
Zacharowski
Paula A
PA
Friedl
Peter
P
Mastan
Parissa
P
Koch
Alexander
A
Boehm
Olaf
O
Rother
Russell P
RP
Reingruber
Sonja
S
Henning
Rainer
R
Emeis
Jef J
JJ
Petzelbauer
Peter
P
D000818:Animals; D018821:CD18 Antigens / Q000737:chemistry; D003497:Cyclic N-Oxides / Q000494:pharmacology; D004195:Disease Models, Animal; D005340:Fibrinogen / Q000737:chemistry* / Q000502:physiology*; D016166:Free Radical Scavengers / Q000737:chemistry; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D009203:Myocardial Infarction / Q000473:pathology; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D015427:Reperfusion Injury / Q000473:pathology*; D013113:Spin Labels
C115499:BBeta fibrinogen; D018821:CD18 Antigens; D003497:Cyclic N-Oxides; D016166:Free Radical Scavengers; D015850:Interleukin-6; D013113:Spin Labels; D005340:Fibrinogen; C001803:tempol