title: Post-conditioning with cyclosporine A fails to reduce the infarct size in an in vivo porcine model.
abstract: BACKGROUND
  Cyclosporine A has generated intense interest in the field of cardioprotection due to its ability to protect the mitochondria at reperfusion by blocking the opening of the mitochondrial permeability transition pore. The aim of our study was to examine the cardioprotective effect of Sandimmun, a clinically available formulation of cyclosporine A, in an in vivo large mammal model.
  
  
  METHODS
  Forty-eight pigs were randomly allocated to one of three groups: (i) Control group (Con, n=19), (ii) Cyclosporine group, (Cyclo, n=19) Sandimmun 10 mg/kg i.v. bolus 5 min before reperfusion and (iii) Pre-conditioning group (Precon, n=10) two cycles of 10 min ischemia interspersed with 30-min reperfusion. The study was further sub-divided into a metabolic protocol, evaluating myocardial metabolism by measuring changes in the interstitial lactate concentration, and a coronary flow protocol. All animals were subjected to 40 min of left anterior descending coronary artery occlusion, followed by 180 min of reperfusion before histochemical staining and assessment of infarct size by planimetry.
  
  
  RESULTS
  Infarct sizes were measured as: Con 51.4 +/- 16.5%, Cyclo 47.3 +/- 15.7% and Precon 2.4 +/- 3.6%, with no significant difference between the Con and Cyclo groups but a highly significant difference between the Precon and Cyclo and Con groups (P<0.0001 for both comparisons). In the Cyclo group, the interstitial lactate concentration was significantly increased compared with the Con group at 6-min reperfusion, although significantly lower at 14 min presumably due to accelerated washout.
  
  
  CONCLUSIONS
  In this large animal model, a 10 mg/kg bolus administration of Sandimmun 5 min before reperfusion did not reduce the infarct size.
authors.affiliation: Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark. rasmus.lie@ki.au.dk
authors.forename: R H
authors.initials: RH
authors.lastname: Lie
authors.forename: N
authors.initials: N
authors.lastname: Stoettrup
authors.forename: E
authors.initials: E
authors.lastname: Sloth
authors.forename: J M
authors.initials: JM
authors.lastname: Hasenkam
authors.forename: R
authors.initials: R
authors.lastname: Kroyer
authors.forename: T T
authors.initials: TT
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D015415:Biomarkers; D003326:Coronary Circulation / Q000502:physiology; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use*; D006439:Hemodynamics / Q000502:physiology; D007166:Immunosuppressive Agents / Q000097:blood / Q000627:therapeutic use*; D019344:Lactic Acid / Q000097:blood; D017551:Microdialysis; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D013552:Swine; D014693:Ventricular Fibrillation / Q000503:physiopathology / Q000517:prevention & control
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D019344:Lactic Acid; D016572:Cyclosporine