Induction of early biomarkers in a thrombus-induced sheep model of ischemic heart failure.

The levels of brain natriuretic peptide (BNP) and monocyte chemoattractant protein-1 (MCP-1) are known to be increased in the sera of subjects with heart failure. Existing models do not account for the biomass of thrombus that occurs in patients undergoing myocardial infarction. In this study, we compared the expressions of sheep-derived genes for BNP, MCP-1, and atrial natriuretic peptide in a new large-animal model of thrombus-induced heart failure. Thrombus of autologous platelets was injected directly into the left circumflex coronary arteries of sheep. Cardiac ischemic injury was evaluated by troponin I levels, and heart failure progression was monitored with the aid of echocardiogram-based evaluation. After outlined time intervals, the sheep were killed and their hearts excised for tissue sampling. Reverse transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay (ELISA) tests were performed to establish gene and protein expressions. At 72 hours after embolization, myocardial BNP and MCP-1 expressions had increased significantly in the ischemic region, compared either with the nonischemic region or with tissue from healthy sheep. As heart failure progressed to 90 days after embolization, the expression of BNP in the ischemic region decreased, whereas its expression in the nonischemic region increased several fold. In contrast, MCP-1 gene expression showed no changes in either tissue after 90 days of embolization. Plasma levels of BNP, determined by Western blot and ELISA, also correlated with the gene-expression studies. Our results show regional changes in BNP and MCP-1, as well as differences in the expression of these 2 genes.