Abstract 3031: Interleukin-11 Attenuates Infarct Size and Improves Ventricular Function in a Canine Heart Model of Ischemia/Reperfusion Injury
Background; Interleukin (IL)-11 is a member of IL-6 cytokine family that is clinically used in hematopoietic disorder. We have previously reported the preconditioning effects of IL-11 against ischemia/reperfusion (I/R) injury through STAT3-mediated antiapoptotic pathway in murine hearts. In order to address the possibility that IL-11 treatment can be a realistic strategy against acute myocardial infarction (AMI), we examined the postconditioning effects of IL-11 in a canine myocardial I/R model.
Method; In open-chest dogs, the left anterior descending artery was occluded for 90 minutes followed by 24 hours of reperfusion with a single intravenous administration of either saline (control, n=8) or IL-11 (8ug/kg, n=8) into the left atrium just before reperfusion. Evans blue/TTC staining identified the area at risk and infarction. Hemodynamic, global and regional left ventricular functional measurements were also compared between two groups.
Results; IL-11 significantly reduced infarct size (21 +/− 11% IL-11 vs. 37 +/− 5.1% control, p=0.02), which was confirmed by lower plasma creatine kinase-MB activity after 2 hours of reperfusion, while there were no differences in the area at risk (39+/−3.5% IL-11 vs. 35+/−6.1% control, p=0.6). Echocardiographic examination revealed that IL-11 administration prevented left ventricular dysfunction at the 24 hours after reperfusion (ejection fraction; 62+/−4.3% IL-11 vs. 50+/−10% control, p=0.02). Furthermore, regional thickening fraction in the ischemic area, which had deteriorated after coronary ligation, showed significant improvement in IL-11 group compared with control group (3.3+/−1.2% vs. −1.8+/−0.7%, p<0.05). Immunohistochemical examination by TUNEL staining revealed that IL-11 significantly reduced apoptotic cell in the ischemic myocardium (15.9+/−3.8% IL-11 vs. 35+/−8.3% control, p<0.001). Increased expression of Bcl-2 was also noted in ischemic area.
Conclusion; IL-11 administered just before reperfusion reduced infarct size and improved global and regional left ventricular function in a canine heart model through the inhibition of myocardial apoptosis in the risk area. IL-11 has significant potential as a novel cytokine therapy to preserve the myocardium against AMI.