title: C4d Deposition Reveals Myocardial Infarction After Cardiac Arrest--Experimental Study.
abstract: BACKGROUND
  The diagnosis of regional myocardial infarction (MI) after cardiac arrest and ischemia-reperfusion injury (IRI) is a major clinical challenge.
  
  
  OBJECTIVE
  We evaluated in a rat cardiac transplantation model whether IRI alone or with MI would induce complement C4d deposition.
  
  
  METHODS
  Isogenic heterotopic cardiac transplantation was performed in 16 Fischer 344 rats to induce IRI, of which 9 rats also underwent ligation of the left anterior coronary artery (LAD) of the heart to yield MI. Histology and qRT-PCR for endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and transforming growth factor β (TGFβ) were performed after cessation of heart beat. C4d was evaluated by immunohistochemistry.
  
  
  RESULTS
  Myocardial inflammation and C4d deposition was increased in grafts with IRI+MI as compared with IRI (0.71 vs. 0.14, PSU, respectively, p<0.04 and 80.13 vs. 20.29, PSU, respectively, p<0.02). The expression of eNOS decreased in grafts with IRI+MI as compared with IRI (p<0.05). Receiver operating characteristic (ROC) curve analysis showed that IRI+MI was associated with C4d deposition (AUC 0.837; S.E. 0.116; p=0.035; 95% C.I. 0.610-1.000).
  
  
  CONCLUSIONS
  Increased C4d deposition may be amenable to identify early MI after cardiac arrest. Early treatment aimed towards complement activation may provide a novel means for induced MI after cardiac arrest.
authors.affiliation: Heart Hospital, Tampere University Hospital, Tampere, Finland.
authors.forename: Vilma
authors.initials: V
authors.lastname: Vuohelainen
authors.affiliation: Department of Pathology, Tampere University Hospital, Tampere, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Paavonen
authors.affiliation: Department of Immunopharmacology, Tampere University, Tampere, Finland.
authors.forename: Mari
authors.initials: M
authors.lastname: Hamalainen
authors.affiliation: Department of Immunopharmacology, Tampere University, Tampere, Finland.
authors.forename: Eeva
authors.initials: E
authors.lastname: Moilanen
authors.affiliation: Heart Hospital, Tampere University Hospital, Tampere, Finland.
authors.forename: Ari A
authors.initials: AA
authors.lastname: Mennander
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015935:Complement C4b / Q000378:metabolism*; D042241:Early Diagnosis; D006323:Heart Arrest / Q000150:complications*; D016027:Heart Transplantation; D009203:Myocardial Infarction / Q000209:etiology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000150:complications*; D009206:Myocardium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000378:metabolism; D011916:Rats, Inbred F344; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D015935:Complement C4b; C032261:complement C4d; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat