title: Potent long-term cardioprotective effects of single low-dose insulin-like growth factor-1 treatment postmyocardial infarction.
abstract: BACKGROUND
  Insulin-like growth factor-1 (IGF-1) is recognized as an important regulator of cardiac structure and cardiomyocyte homeostasis. The prosurvival and antiapoptotic effects of IGF-1 have been investigated in vitro and in rodent models of myocardial infarction (MI). However, the clinical application of IGF-1 has been hampered by dose-dependent side effects both acutely and during chronic administration. We hypothesized that single, low-dose IGF-1 (LD-IGF-1) administered locally and early in the reperfusion phase after acute MI in a large animal model would avoid significant side effects but would have prosurvival effects that would manifest in long-term structural and functional improvement after MI treatment.
  
  
  RESULTS
  Forty-four female Landrace pigs underwent intracoronary administration of LD-IGF-1 or saline 2 hours into the reperfusion phase of acute left anterior descending artery occlusion MI. In the area of infarction, IGF-1 receptor and signaling responses were activated at 30 minutes and cardiomyocyte cell death attenuated at 24 hours after LD-IGF-1 but not saline treatment. Hemodynamic and structural studies using pressure-volume loop, CT, and triphenyltetrazolium chloride analysis 2 months post-MI confirmed a marked reduction in infarct size, attenuation of wall thinning, and augmentation of wall motion in the LD-IGF-1-treated but not in the saline-treated animals. These regional structural benefits were associated with global reductions in left ventricular volumes and significant improvement in left ventricular systolic and diastolic function.
  
  
  CONCLUSIONS
  One-time LD-IGF-1 effects potent acute myocardial salvage in a preclinical model of left anterior descending artery occlusive MI, extending to long-term benefits in MI size, wall structure, and function and underscoring its potential as an adjunctive therapeutic agent.
authors.affiliation: Centre for Research in Vascular Biology and Cell Biology Laboratory, Department of Biochemistry, Biosciences Institute, University College Cork, Cork, Ireland.
authors.forename: John F
authors.initials: JF
authors.lastname: O'Sullivan
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Leblond
authors.forename: Geraldine
authors.initials: G
authors.lastname: Kelly
authors.forename: Arun H S
authors.initials: AH
authors.lastname: Kumar
authors.forename: Pat
authors.initials: P
authors.lastname: Metharom
authors.forename: Chirlei K
authors.initials: CK
authors.lastname: Büneker
authors.forename: Niki
authors.initials: N
authors.lastname: Alizadeh-Vikali
authors.forename: Ivalina
authors.initials: I
authors.lastname: Hristova
authors.forename: Brian G
authors.initials: BG
authors.lastname: Hynes
authors.forename: Rosemary
authors.initials: R
authors.lastname: O'Connor
authors.forename: Noel M
authors.initials: NM
authors.lastname: Caplice
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002985:Clinical Protocols; D005260:Female; D006439:Hemodynamics; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000009:adverse effects; D023421:Models, Animal; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D013318:Stroke Volume; D013552:Swine; D013778:Tetrazolium Salts / Q000378:metabolism; D013997:Time Factors
chemical_list: D013778:Tetrazolium Salts; D007334:Insulin-Like Growth Factor I; C009591:triphenyltetrazolium; D017526:Receptor, IGF Type 1