BACKGROUND:
We tested whether intra-coronary administration of cyclosporine effectively preserves left ventricular (LV) function in porcine acute anterior wall infarction (AMI).
METHODS AND RESULTS:
Eighteen male mini-pigs were randomized into groups 1 (control), 2 (AMI alone), and 3 (AMI with cyclosporine treatment). AMI was induced by ligating middle left anterior descending artery (LAD). Fifteen minutes after ligation, saline and cyclosporine (2.5 mg) combination was injected into LAD beyond ligation in groups 2 and 3, respectively. Echocardiography was performed after 14 days, followed by animal sacrifice. Larger infarcted area (IA) was noted in group 2 than in group 3 (p < 0.001). In both IA and peri-IA, mRNA expressions of IL-8, MMP-9, caspase 3 and Bax were higher, whereas PGC-1α, eNOS and Bcl-2 were lower in group 2 than in groups 1 and 3 (p < 0.01). The mRNA expression of IL-10 was upregulated in both IA and peri-IA in group 3 compared with groups 1 and 2. Apoptotic nuclei and CD40-positive cells were higher in both peri-IA and non-IA in group 2 than in groups 1 and 3 (p < 0.001). Oxidative stress and cytosolic cytochrome C in IA were increased in group 2 than in groups 1 and 3 (p < 0.001). Mid-LV end-systolic areas were higher, whereas mid-LV wall fractional area change was lower in group 2 than in groups 1 and 3 (p < 0.001).
CONCLUSIONS:
Intra-coronary administration of cyclosporine effectively limits infarct size, attenuates LV remodeling and preserves LV function.
