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

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.

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