title: Intracoronary application of C1 esterase inhibitor improves cardiac function and reduces myocardial necrosis in an experimental model of ischemia and reperfusion.
abstract: BACKGROUND
  Myocardial injury from ischemia can be aggravated by reperfusion of the jeopardized area. The precise underlying mechanisms have not been clearly defined, but proinflammatory events, including complement activation, leukocyte adhesion, and infiltration and release of diverse mediators, probably play important roles. The present study addresses the possibility of reducing reperfusion damage by the application of C1 esterase inhibitor (C1-INH).
  
  
  RESULTS
  Cardioprotection by C1-INH 20 IU/kg IC was examined in a pig model with 60 minutes of coronary occlusion, followed by 120 minutes of reperfusion. C1-INH was administered during the first 5 minutes of coronary reperfusion Compared with the NaCl controls, C1-INH reduced myocardial injury (48.8 +/- 7.8% versus 73.4 +/- 4.0% necrosis of area at risk, P < or = .018). C1-INH treatment significantly reduced circulating C3a and slightly attenuated C5a plasma concentrations. Myocardial protection was accompanied by reduced plasma concentration of creatine kinase and troponin-T. C1-INH had no effect on global hemodynamic parameters, but local myocardial contractility was markedly improved in the ischemic zone. In the short-axis view, 137 degrees of the anteroseptal region showed significantly improved wall motion at early and 29 degrees at late reperfusion with C1-INH treatment.
  
  
  CONCLUSIONS
  C1-INH significantly protects ischemic tissue from reperfusion damage, reduces myocardial necrosis, and improves local cardiac function.
authors.affiliation: Johannes Gutenberg-University Mainz, Second Medical Clinic, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Horstick
authors.forename: A
authors.initials: A
authors.lastname: Heimann
authors.forename: O
authors.initials: O
authors.lastname: Götze
authors.forename: G
authors.initials: G
authors.lastname: Hafner
authors.forename: O
authors.initials: O
authors.lastname: Berg
authors.forename: P
authors.initials: P
authors.lastname: Böhmer
authors.forename: P
authors.initials: P
authors.lastname: Becker
authors.forename: H
authors.initials: H
authors.lastname: Darius
authors.forename: H J
authors.initials: HJ
authors.lastname: Rupprecht
authors.forename: M
authors.initials: M
authors.lastname: Loos
authors.forename: S
authors.initials: S
authors.lastname: Bhakdi
authors.forename: J
authors.initials: J
authors.lastname: Meyer
authors.forename: O
authors.initials: O
authors.lastname: Kempski
mesh_terms: D000706:Anaphylatoxins / Q000032:analysis; D000818:Animals; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D003331:Coronary Vessels / Q000503:physiopathology; D003402:Creatine Kinase / Q000378:metabolism; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D007267:Injections; D019344:Lactic Acid / Q000097:blood; D008297:Male; D017202:Myocardial Ischemia / Q000473:pathology* / Q000503:physiopathology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D009336:Necrosis; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D013552:Swine; D014336:Troponin / Q000378:metabolism; D020107:Troponin T
chemical_list: D000706:Anaphylatoxins; D003174:Complement C1 Inactivator Proteins; D014336:Troponin; D020107:Troponin T; D019344:Lactic Acid; D003402:Creatine Kinase; D010100:Oxygen