With the complexities that surround myocardial ischemia/reperfusion (MI/R) injury, therapies adjunctive to reperfusion that elicit beneficial pleiotropic effects and do not overlap with standard of care are necessary. This study found that the mitochondrial-derived peptide S14G-humanin (HNG) (2 mg/kg), an analogue of humanin, reduced infarct size in a large animal model of MI/R. However, when ischemic time was increased, the infarct-sparing effects were abolished with the same dose of HNG. Thus, although the 60-min MI/R study showed that HNG cardioprotection translates beyond small animal models, further studies are needed to optimize HNG therapy for longer, more patient-relevant periods of cardiac ischemia.
Keywords: AAR, area-at-risk; Bax, Bcl-2–associated X protein; DAPI, 4′,6-diamidino-2-phenylindole; ELISA, enzyme-linked immunoadsorbent assay; HNG, S14G-humanin analogue; IGFBP3, insulin-like growth factor–binding protein-3; IV, intravenously; LAD, left anterior coronary artery; LV, left ventricular; MDP, mitochondrial-derived peptide; MI, myocardial infarction; MI/R, myocardial ischemia/reperfusion; NIZ, nonischemic zone; RMBF, regional myocardial blood flow; STAT, signal transducer and activator of transcription; TBARS, thiobarbituric acid–reactive substances; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling; acute myocardial infarction; adjunctive therapy; cTnI, cardiac troponin I; h-FABP, heart fatty acid–binding protein; large animal model; mitochondrial-derived peptide; myocardial ischemia-reperfusion injury.
© 2020 The Authors.