title: Intracoronary insulin administered at reperfusion in a porcine model of acute coronary syndrome.
abstract: BACKGROUND
  Experimental studies have demonstrated that insulin elicits cardioprotection in coronary occlusion-reperfusion models. We studied the effects of intracoronary insulin on regional cardiac function in a porcine model with reperfusion after a critical coronary artery stenosis.
  
  
  METHODS
  In 20 anaesthetized pigs with an extracorporeal shunt from the brachiocephalic to the left anterior descending coronary artery, a fixed stenosis was applied, obtaining 50% reduction of shunt flow for 60 min. Intracoronary insulin 1 1U [DOSAGE ERROR CORRECTED] or 0.9% saline was infused for 15 min, starting 5 min prior to initiation of 180 min of reperfusion. Microsphere injections confirmed ischaemia and reperfusion. Epicardial echocardiographic multilayer radial tissue Doppler strain and strain rate and one-layer speckle-tracking strain evaluated myocardial function. Apoptosis was evaluated by cleaved caspase-3 activity. Area at risk and infarct size were determined with Evans Blue and triphenyltetrazolium chloride staining.
  
  
  RESULTS
  In both groups, the area at risk constituted approximately 26% of the left ventricular mass. Minor areas of infarction were predominantly seen subendocardially, where tissue blood flow rate was severely reduced during stenosis. After 180 min of reperfusion, recovery of speckle-tracking circumferential strain averaged 57.5 ± 11.4% of baseline values in insulin treated animals compared to 22.3 ± 8.7% in controls (p = 0.025). Multilayer radial strain and strain rate did not differ between groups. Cleaved caspase-3 activity was most prominent in the subepicardial layer in the saline-treated group.
  
  
  CONCLUSIONS
  Intracoronary insulin at the onset of reperfusion alleviated regional myocardial dysfunction in acute ischaemia-reperfusion and was associated with a reduction of apoptosis.
authors.affiliation: Department of Heart Disease, Haukeland University Hospital, Bergen, Norway Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Norway piri@helse-bergen.no.
authors.forename: Pirjo-Riitta
authors.initials: PR
authors.lastname: Salminen
authors.affiliation: Department of Heart Disease, Haukeland University Hospital, Bergen, Norway Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Norway.
authors.forename: Geir Olav
authors.initials: GO
authors.lastname: Dahle
authors.affiliation: Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Norway.
authors.forename: Christian Arvei
authors.initials: CA
authors.lastname: Moen
authors.affiliation: Department of Biomedicine, Faculty of Medicine and Dentistry, University of Bergen, Norway.
authors.forename: Anne Kristine
authors.initials: AK
authors.lastname: Jonassen
authors.affiliation: Department of Heart Disease, Haukeland University Hospital, Bergen, Norway Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Norway.
authors.forename: Rune
authors.initials: R
authors.lastname: Haaverstad
authors.affiliation: Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Norway.
authors.forename: Knut
authors.initials: K
authors.lastname: Matre
authors.affiliation: Department of Clinical Science, Faculty of Medicine and Dentistry, University of Bergen, Norway.
authors.forename: Ketil
authors.initials: K
authors.lastname: Grong
mesh_terms: D054058:Acute Coronary Syndrome / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D023921:Coronary Stenosis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control; D015425:Myocardial Reperfusion / Q000379:methods*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011897:Random Allocation; D013552:Swine
chemical_list: D007328:Insulin; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3
keywords: Acute coronary syndrome; echocardiography; insulin; ischaemia-reperfusion