Intra-coronary administration of cyclosporine limits infarct size, attenuates remodeling and preserves left ventricular function in porcine acute anterior infarction.
BACKGROUND
We tested whether intra-coronary administration of cyclosporine effectively preserves left ventricular (LV) function in porcine acute anterior wall infarction (AMI).


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.
Sheu
Jiunn-Jye
JJ
Division of Cardiovascular Surgery, Department of Surgery, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan, ROC.
Chua
Sarah
S
Sun
Cheuk-Kwan
CK
Chang
Li-Teh
LT
Yen
Chia-Hung
CH
Wu
Chiung-Jen
CJ
Fu
Morgan
M
Yip
Hon-Kan
HK
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016572:Cyclosporine / Q000008:administration & dosage*; D007269:Injections, Intra-Arterial; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018384:Oxidative Stress / Q000502:physiology; D011897:Random Allocation; D013552:Swine; D013556:Swine, Miniature; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects* / Q000502:physiology
D016572:Cyclosporine