title: Reperfusion therapy with low-dose insulin or insulin-like growth factor 2; myocardial function and infarct size in a porcine model of ischaemia and reperfusion.
abstract: In an open-chest porcine model, we examined whether myocardial pharmacological conditioning at the time of reperfusion with low-dose insulin or insulin-like growth factor 2 (IGF2), not affecting serum glucose levels, could reduce infarct size and improve functional recovery. Two groups of anaesthetized pigs with either 60 or 40 min. of left anterior descending artery occlusion (total n = 42) were randomized to receive either 0.9% saline, insulin or IGF2 infusion for 15 min., starting 5 min. before a 180-min. reperfusion period. Repeated fluorescent microsphere injections were used to confirm ischaemia and reperfusion. Area at risk and infarct size was determined with Evans blue and triphenyltetrazolium chloride staining. Local myocardial function was evaluated with multi-layer radial tissue Doppler strain and speckle-tracking strain from epicardial echocardiography. Western blotting and TUNEL staining were performed to explore apoptosis. Infarct size did not differ between treatment groups and was 56.7 ± 6.8%, 49.7 ± 9.6%, 56.2 ± 8.0% of area at risk for control, insulin and IGF2 group, respectively, in the 60-min. occlusion series. Corresponding values were 45.6 ± 6.0%, 48.4 ± 7.2% and 34.1 ± 5.8% after 40-min. occlusion. Global and local cardiac function did not differ between treatment groups. No differences related to treatment could be found in myocardial tissue cleaved caspase-3 content or the degree of TUNEL staining. Reperfusion therapy with low-dose insulin or with IGF2 neither reduced infarct size nor improved function in reperfused myocardium in this in vivo porcine model.
authors.affiliation: Section of Cardiothoracic Surgery, Department of Heart Disease, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Pirjo-Riitta
authors.initials: PR
authors.lastname: Salminen
authors.forename: Geir Olav
authors.initials: GO
authors.lastname: Dahle
authors.forename: Christian Arvei
authors.initials: CA
authors.lastname: Moen
authors.forename: Anita
authors.initials: A
authors.lastname: Wergeland
authors.forename: Anne Kristin
authors.initials: AK
authors.lastname: Jonassen
authors.forename: Rune
authors.initials: R
authors.lastname: Haaverstad
authors.forename: Knut
authors.initials: K
authors.lastname: Matre
authors.forename: Ketil
authors.initials: K
authors.lastname: Grong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D004195:Disease Models, Animal; D004452:Echocardiography; D005260:Female; D020287:In Situ Nick-End Labeling; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007335:Insulin-Like Growth Factor II / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D013552:Swine; D013997:Time Factors
chemical_list: D007328:Insulin; D007335:Insulin-Like Growth Factor II
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