Abstract
There are almost no drugs that can be given to patients with myocardial infarction (MI) after coronary artery (CA) reperfusion (R) to protect against heart failure (HF) following myocardial infarction. A key reason for this is that almost all cardioprotective drugs are effective before CA occlusion (O), but not after CAR, and it is not practical to treat patients prior to CAO. We examined the antiviral drug, AraAde, which has cardioprotective actions of selective adenylyl cyclase isoform type 5 (AC5) inhibition and a structure resembling a potent cardioprotective agent, adenosine. When vehicle was administered to mice after 30 min CAO/CAR, HF developed over the next 4 weeks, characterized by reduced left ventricular ejection fraction (48 ± 2.7%). In mice treated with AraAde after CAR, the ejection fraction was improved (57 ± 2.0%, p<0.05) and the resultant myocardial fibrosis was less (AraAde 2.7 ± 0.2 % vs. vehicle 5.8 ± 0.5%, p<0.05), as was the myocyte apoptosis (AraAde 0.04 ± 0.03% vs. vehicle 0.14 ± 0.03%, p<0.05). Thus, AraAde is a novel drug that inhibits adenylyl cyclase type 5 and protects the heart from development of MI induced HF, when delivered after CAR, a key clinically useful feature, where patients with MI require CAR immediately.
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