C4d Deposition Reveals Myocardial Infarction After Cardiac Arrest--Experimental Study

Adv Clin Exp Med. 2015 May-Jun;24(3):393-9. doi: 10.17219/acem/29181.

Abstract

Background: The diagnosis of regional myocardial infarction (MI) after cardiac arrest and ischemia-reperfusion injury (IRI) is a major clinical challenge.

Objectives: We evaluated in a rat cardiac transplantation model whether IRI alone or with MI would induce complement C4d deposition.

Material and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Complement C4b / metabolism*
  • Early Diagnosis
  • Heart Arrest / complications*
  • Heart Transplantation
  • Myocardial Infarction / etiology*
  • Myocardial Infarction / genetics
  • Myocardial Infarction / immunology
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / pathology
  • Myocardial Reperfusion Injury / complications*
  • Myocardium / immunology
  • Myocardium / metabolism*
  • Myocardium / pathology
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism
  • Peptide Fragments / metabolism*
  • Predictive Value of Tests
  • RNA, Messenger / metabolism
  • Rats, Inbred F344
  • Time Factors
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation

Substances

  • Biomarkers
  • Peptide Fragments
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Complement C4b
  • complement C4d
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos2 protein, rat
  • Nos3 protein, rat