title: Antiapoptotic intervention in repeated blood cardioplegia: a porcine study of myocardial function.
abstract: BACKGROUND
  Lethal reperfusion injury has been associated with apoptotic cell death. Insulin and insulin-like growth factors (IGF-I/IGF-II) may modulate this cell death when administered at the onset of reperfusion after ischemia. We explored if antiapoptotic treatment with IGF-II could influence left ventricular function in an experimental model with cardiopulmonary bypass and repeated oxygenated blood cardioplegia.
  
  
  METHODS
  Twenty pigs underwent cardiopulmonary bypass with aortic cross-clamping for 60 minutes. In controls, hearts were arrested with cold, oxygenated blood cardioplegia repeated after 20 and 40 minutes. In the intervention group IGF-II was added to the cardioplegic solution at 20 and 40 minutes. After declamping and weaning from cardiopulmonary bypass, left ventricular global and local function was evaluated with a conductance catheter and tissue velocity imaging. Three hours after declamping the anterior left ventricle wall was divided in three layers and studied for blood flow rate with microspheres, Akt phosphorylation, and caspase-3 cleavage. Troponin-T levels were measured at baseline and after 3 hours of reperfusion.
  
  
  RESULTS
  A reduction of myocardial levels of cleaved caspase-3 (p < 0.001) was found in the subendocardial wall layer and serum troponin-T was reduced (p < 0.025) in the IGF-II group 3 hours after declamping. In the IGF-II treated animals, left ventricular preload recruitable stroke work was low 1 hour after declamping and increased to levels higher than in controls (p < 0.025) 3 hours after declamping. Other cardiac variables did not differ between groups.
  
  
  CONCLUSIONS
  When added to repeated cold blood cardioplegia, IGF-II reduces apoptosis and ischemia-reperfusion injury with minor effects on cardiac function.
authors.affiliation: Section of Cardiothoracic Surgery, Department of Heart Disease, Haukeland University Hospital, Bergen, Norway. piri@helse-bergen.no
authors.forename: Pirjo-Riitta
authors.initials: PR
authors.lastname: Salminen
authors.forename: Anne Kristin
authors.initials: AK
authors.lastname: Jonassen
authors.forename: Eva-Katrine
authors.initials: EK
authors.lastname: Aarnes
authors.forename: Chistian Arvei
authors.initials: CA
authors.lastname: Moen
authors.forename: Lodve
authors.initials: L
authors.lastname: Stangeland
authors.forename: Finn
authors.initials: F
authors.lastname: Eliassen
authors.forename: Ruth
authors.initials: R
authors.lastname: Kongsvik
authors.forename: Knut
authors.initials: K
authors.lastname: Matre
authors.forename: Rune
authors.initials: R
authors.lastname: Haaverstad
authors.forename: Ketil
authors.initials: K
authors.lastname: Grong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006324:Heart Arrest, Induced; D007335:Insulin-Like Growth Factor II / Q000627:therapeutic use; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D013552:Swine; D020107:Troponin T / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
chemical_list: D002314:Cardioplegic Solutions; D020107:Troponin T; D007335:Insulin-Like Growth Factor II; D053148:Caspase 3