2009 Southern Regional Meeting Abstracts

Purpose of Study: Apoptosis & inflammation are two key pathological features of post-infarction remodeling. Interleukin-1 (IL-1) signaling is involved in both apoptosis & inflammation in response to ischemia. We hypothesized that during ischemia, IL-1 receptor antagonist (IL-1Ra), an endogenous IL-1 inhibitor, plays a protective role & therefore mice lacking the IL-1Ra gene (knock out - KO) would be more susceptible to apoptosis & adverse cardiac remodeling after acute myocardial infarction (AMI).
Methods Used: Seven KO mice & 8 age-matched wild-type (WT) mice underwent surgical ligation of the left coronary artery. All animals underwent transthoracic echocardiography before surgery & at day 7. Infarct size and cardiomyocyte apoptosis were measured using collagen staining & in situ detection of DNA fragmentation, respectively.
Summary of Results: Seven days after AMI, KO mice showed increased left ventricular end-diastolic diameter & end-systolic diameter with reduced fractional shortening vs WT mice [Figure]. An average of 5 aneurysmatic segments were seen in the KO mice vs 1 segment in the WT mouse (p=0.010). KO mice also had a significantly larger area of scar (35±2% vs 23±2%, p=0.009) & significantly greater cardiomyocyte apoptosis in the peri-infarct myocardium (9.5±2.2% vs 1.9±0.1%, p=0.022) compared to WT mice.
Conclusions: Endogenous IL-1Ra protects cardiomyocytes from apoptosis, prevents adverse cardiac remodeling & aneurysm formation after AMI. The cardioprotective effect of endogenous IL-1Ra on apoptosis affirms a role for IL-1 signaling & the potential for IL-1 based treatment strategies to prevent heart failure after AMI.