title: Pre-treatment with glucagon-like Peptide-1 protects against ischemic left ventricular dysfunction and stunning without a detected difference in myocardial substrate utilization.
abstract: OBJECTIVE
  This study sought to determine whether pre-treatment with intravenous glucagon-like peptide-1 (GLP-1)(7-36) amide could alter myocardial glucose use and protect the heart against ischemic left ventricular (LV) dysfunction during percutaneous coronary intervention.
  
  
  BACKGROUND
  GLP-1 has been shown to have favorable cardioprotective effects, but its mechanisms of action remain unclear.
  
  
  METHODS
  Twenty patients with preserved LV function and single-vessel left anterior descending coronary artery disease undergoing elective percutaneous coronary intervention were studied. A conductance catheter was placed into the LV, and pressure-volume loops were recorded at baseline, during 1-min low-pressure balloon occlusion (BO), and at 30-min recovery. Patients were randomized to receive an infusion of either GLP-1(7-36) amide at 1.2 pmol/kg/min or saline immediately after baseline measurements. Simultaneous coronary artery and coronary sinus blood sampling was performed at baseline and after BO to assess transmyocardial glucose concentration gradients.
  
  
  RESULTS
  BO caused both ischemic LV dysfunction and stunning in the control group but not in the GLP-1 group. Compared with control subjects, the GLP-1 group had a smaller reduction in LV performance during BO (delta dP/dTmax, -4.3 vs. -19.0%, p = 0.02; delta stroke volume, -7.8 vs. -26.4%, p = 0.05), and improved LV performance at 30-min recovery. There was no difference in transmyocardial glucose concentration gradients between the 2 groups.
  
  
  CONCLUSIONS
  Pre-treatment with GLP-1(7-36) amide protects the heart against ischemic LV dysfunction and improves the recovery of function during reperfusion. This occurs without a detected change in myocardial glucose extraction and may indicate a mechanism of action independent of an effect on cardiac substrate use. (Effect of Glucgon-Like-Peptide-1 [GLP-1] on Left Ventricular Function During Percutaneous Coronary Intervention [PCI]; ISRCTN77442023).
authors.affiliation: Department of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Liam M
authors.initials: LM
authors.lastname: McCormick
authors.affiliation: Department of Interventional Cardiology, Papworth Hospital, Cambridge, United Kingdom.
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hoole
authors.affiliation: Department of Medical Physics and Clinical Engineering, Cambridge University Hospital National Health Service Foundation Trust, Cambridge, United Kingdom.
authors.forename: Paul A
authors.initials: PA
authors.lastname: White
authors.affiliation: Department of Interventional Cardiology, Papworth Hospital, Cambridge, United Kingdom.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Read
authors.affiliation: Department of Medical Physics and Clinical Engineering, Cambridge University Hospital National Health Service Foundation Trust, Cambridge, United Kingdom.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Axell
authors.affiliation: Department of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Sophie J
authors.initials: SJ
authors.lastname: Clarke
authors.affiliation: Department of Interventional Cardiology, Papworth Hospital, Cambridge, United Kingdom.
authors.forename: Michael
authors.initials: M
authors.lastname: O'Sullivan
authors.affiliation: Department of Interventional Cardiology, Papworth Hospital, Cambridge, United Kingdom.
authors.forename: Nick E J
authors.initials: NEJ
authors.lastname: West
authors.affiliation: Department of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom. Electronic address: dpd24@medschl.cam.ac.uk.
authors.forename: David P
authors.initials: DP
authors.lastname: Dutka
mesh_terms: D006328:Cardiac Catheterization; D003327:Coronary Disease / Q000601:surgery*; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D054795:Incretins / Q000008:administration & dosage / Q000627:therapeutic use*; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000517:prevention & control*; D017682:Myocardial Stunning / Q000517:prevention & control*; D062645:Percutaneous Coronary Intervention; D016896:Treatment Outcome; D018487:Ventricular Dysfunction, Left / Q000517:prevention & control*
chemical_list: D054795:Incretins; D052216:Glucagon-Like Peptide 1
keywords: angioplasty; cardioprotection; glucagon-like peptide-1; myocardial ischemia; myocardial stunning; myocardial substrate use