Abstract 19457: Cardioprotective Effects of the Novel Mitochondrial-Derived Peptide, Humanin, in a Porcine Model of Myocardial Ischemia-Reperfusion Injury
Background: Humanin, a novel mitochondria-associated peptide, has previously been shown to exert potent cytoprotective and anti-apoptotic effects in rodent models of myocardial ischemia/reperfusion (MI/R).
Objective: We investigated the effects of humanin on the severity of myocardial infarction in a clinically relevant porcine model of MI/R injury.
Methods and Results: Female Yucatan miniswine (n=7) were subjected to balloon-occlusion of the left anterior descending coronary artery (LAD) for 75 min. followed by 48 hr. of reperfusion. Pigs received a single bolus of humanin (2 mg/Kg, i.v.) or vehicle 5 min. before reperfusion. Myocardial area-at-risk and infarction was assessed using ex vivo Phthalo blue and 2,3,5- Triphenyltetrazolium chloride (TTC) staining. The extent of myocardial cell death was determined using circulating troponin-I levels. Humanin significantly (p = 0.0017) reduced myocardial infarct size per area-at-risk by 24% compared to vehicle. Futhermore, circulating cardiac troponin-I levels trended lower in swine treated with humanin compared to vehicle treated animals.
Conclusions: These data demonstrate that acute humanin therapy at the time of reperfusion protects against myocardial infarction in a translational model of MI/R injury. Studies are currently underway to confirm these preliminary results and define the mechanisms by which humanin protects the ischemic porcine myocardium. Humanin may prove beneficial for the treatment of acute MI in patients.
Author Disclosures: C.L. Organ: None. M.J. Ali: None. A. Scarborough: None. A. Rushing: None. S. Boisvert: None. Z. Gong: None. D.J. Lefer: Other; Modest; U.S. Patent. R. Muzumdar: Other; Modest; U.S. Patent. T.T. Goodchild: None.
- © 2016 by American Heart Association, Inc.