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Cardioprotective Effects by a Novel Opioid Peptide in Myocardial Ischemia/Reperfusion Injury
Author(s) -
Kim Hanna,
McIntyre Anahi,
Woodley John,
Lopez Alexandra,
Dittakavi Tejaswi,
Finnegan Matthew,
Amuquandoh Kevin,
Ambrosino Maxwell,
Walker Kiana,
Patel Harsh,
Chen Qian,
Barsotti Robert,
Young Lindon H.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.717.23
Subject(s) - cardioprotection , peptide , (+) naloxone , opioid peptide , medicine , ischemia , pharmacology , reperfusion injury , antagonist , receptor , opioid antagonist , opioid , anesthesia , endocrinology , chemistry , biochemistry
Preliminary studies in mice have shown that a novel tri‐peptide (Phe‐D‐Arg‐Phe‐Amide, MW=468 g/mol) attenuates ventilation induced diaphragm dysfunction when given as a pretreatment. Tri‐peptide is structurally similar to the SS‐20 peptide (Phe‐D‐Arg‐Phe‐Lys‐Amide), which has been shown to be cardioprotective when given before ischemia, but thought not to have opioid properties (Cho et al., 2007). Our study aims to determine whether pre‐ or posttreatment with tri‐peptide is more efficacious in attenuating the deleterious effects of myocardial ischemia/reperfusion (I/R) injury and whether this cardioprotection is mediated by opioid receptor activation. This was tested by observing whether tri‐peptide‐induced cardioprotection was abolished when administered in conjunction with naloxone, a nonselective opioid receptor antagonist. Tri‐peptide (50μM) was administered prior to I (pretreatment, n=8) or during R (posttreatment, n=8) in isolated perfused rat hearts subjected to I(30 min)/R(45 min) and compared to untreated control hearts (n=7) and hearts pre‐treated with tri‐peptide (50 μM) + naloxone (Nlx, 10μM, n=8). Tri‐peptide pretreatment hearts significantly recovered post‐reperfused left ventricular developed pressure (LVDP) to 59±6% of initial baseline values compared to untreated control, posttreatment tri‐peptide, and pretreatment tri‐peptide + Nlx hearts in which LVDP recovered to only 33±7%, 34±8%, and 26±4% of initial baseline values respectively (p<0.01). Furthermore, tri‐peptide pretreatment hearts exhibited significantly reduced infarct sizes of 26±1% compared to untreated control and posttreatment tri‐peptide hearts, in which infarct sizes were 38±4% and 37±2% respectively (p<0.05) assessed using 1% triphenyltetrazolium chloride staining. Pretreated tripeptide + Nlx hearts showed infarct sizes of 32±3% which was not significantly different from untreated controls. These data suggest that pretreatment and not posttreatment with this novel tri‐peptide was cardioprotective and that this protection was mediated via opioid receptor activation. Future studies will attempt to determine the specific opioid receptor subtype involved in tri‐peptide cardioprotection by testing whether delta or kappa opioid receptor antagonists block the cardioprotective effects of tri‐peptide pretreatment. Support or Funding Information This study was supported by the Center for Chronic Disorders of Aging, the Division of Research and the Department of Bio‐Medical Sciences at Philadelphia College of Osteopathic Medicine. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .