Effects of liraglutide and ischemic postconditioning on myocardial salvage after I/R injury in pigs.
OBJECTIVE
Acute STEMI is routinely treated by acute PCI. This treatment may itself damage the tissue (reperfusion injury). Conditioning with GLP-1 analogs has been shown to reduce reperfusion injury. Likewise, ischemic postconditioning provides cardioprotection following STEMI. We tested if combined conditioning with the GLP-1 analog liraglutide and ischemic postconditioning offered additive cardioprotective effect after reperfusion of 45 min coronary occlusion of left anterior descending artery (LAD).


METHODS
Fifty-eight non-diabetic female Danish Landrace pigs (60 ± 10kg) were randomly assigned to four groups. Myocardial infarction (MI) was induced by occluding the LAD for 45 min. Group 1 (n = 14) was treated with i.v. liraglutide after 15 min of ischemia. Group 2 (n = 17) received liraglutide treatment concomitant with ischemic postconditioning, after 45 min of ischemia. Group 3 (n = 15) recieved ischemic postconditioning and group 4 (n = 12) was kept as controls.


RESULTS
No intergroup differences in relative infarct size were detected (overall mean 57 ± 3%; p = 0.68). Overall mortality was 34% (CI 25-41%) including 26% post-intervention, with no intergroup differences (p = 0.99). Occurrence of ventricular fibrillation (VF) was 59% (CI 25-80%) including 39% postintervention with no intergroup differences (p = 0.65).


CONCLUSIONS
In our closed-chest pig-model, we were unable to detect any cardioprotective effect of liraglutide or ischemic postconditioning either alone or combined.
a Department of Cardiology, Nephrology and Endocrinology , Nordsjællands Hospital , Hillerød , Denmark.|b Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
Kathrine
K
Ekström
c Department of Cardiology , Rigshospitalet , Copenhagen , Denmark.
Morten
M
Dalsgaard
a Department of Cardiology, Nephrology and Endocrinology , Nordsjællands Hospital , Hillerød , Denmark.
Kasper
K
Iversen
a Department of Cardiology, Nephrology and Endocrinology , Nordsjællands Hospital , Hillerød , Denmark.
Ulrik
U
Pedersen-Bjergaard
c Department of Cardiology , Rigshospitalet , Copenhagen , Denmark.
Niels
N
Vejlstrup
a Department of Cardiology, Nephrology and Endocrinology , Nordsjællands Hospital , Hillerød , Denmark.|b Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
Sarah Seberg
SS
Diemar
d Department of Hematology , Center for Cancer Immune Therapy, Herlev Hospital Denmark , Herlev , Denmark.
Manja
M
Idorn
a Department of Cardiology, Nephrology and Endocrinology , Nordsjællands Hospital , Hillerød , Denmark.|b Faculty of Health and Medical Sciences , University of Copenhagen , Copenhagen , Denmark.
Birger
B
Thorsteinsson
c Department of Cardiology , Rigshospitalet , Copenhagen , Denmark.
Thomas
T
Engstrøm
D000818:Animals; D021721:Balloon Occlusion; D003131:Combined Modality Therapy; D004195:Disease Models, Animal; D005260:Female; D054795:Incretins / Q000494:pharmacology*; D057775:Ischemic Postconditioning / Q000009:adverse effects / Q000379:methods*; D000069450:Liraglutide / Q000494:pharmacology*; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D009206:Myocardium / Q000473:pathology*; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects*; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013552:Swine; D014693:Ventricular Fibrillation / Q000209:etiology
D054795:Incretins; D000069450:Liraglutide
Cardioprotection; ischemia-reperfusion injury; ischemic postconditioning; liraglutide