Innate immune response after acute myocardial infarction and pharmacomodulatory action of tacrolimus in reducing infarct size and preserving myocardial integrity

Background: this study investigated the association between innate immune reaction and myocardial damage after acute myocardial infarction (ami) and anti-inflammatory role of tacrolimus in reducing infarct size. male mini-pigs (n=18) were equally categorized into sham control (sc),untreated ami (by ligation of left anterior descending coronary artery),and ami-tacrolimus (ami-tac) (0.5 mg intra-coronary injection 30 minutes post-ami). cardiac magnetic resonance imaging (mri) was performed at post-ami days 2,5 and 21 before sacrificing the animals. results: by post-ami day 21,left ventricular ejection fraction (lvef) was lowest in untreated ami animals,significantly higher in sc than in ami-tac group (all p<0.003). infarct areas at basal,middle,and apical levels,numbers of cd14+ and inos+ cells in infarct area (ia) and peri-ia,and protein expression of cd14,cd68,and ly6g from circulating inflammatory cells showed an opposite pattern compared with that of lvef in all groups (all p<0.005). protein expressions of mcp-1,mip-1,tnf-α,nf-κb,inos,and il-12 in ia and peri-ia exhibited an identical pattern compared to that of cd14,cd68,and ly6g from circulating inflammatory cells (all p<0.01). expressions of myocardial damage biomarkers in ia and peri-ia [γ-h2ax,β-myosin heavy chain (mhc),smad3,tgf-β] were highest in ami and higher in ami-tac than in sc,whereas expressions of myocardial integrity biomarkers (connexin43,mitochondrial cytochrome-c,α-mhc,bmp-2,smad1/5) were opposite to those of damage biomarkers (all p<0.001). conclusion: innate immune responses were markedly augmented and lvef was significantly reduced after ami but were remarkably improved after tacrolimus treatment. © 2013 sheu et al.; licensee biomed central ltd.