title: Effect of cyclosporine on reperfusion injury in acute myocardial infarction.
abstract: BACKGROUND
  Experimental evidence suggests that cyclosporine, which inhibits the opening of mitochondrial permeability-transition pores, attenuates lethal myocardial injury that occurs at the time of reperfusion. In this pilot trial, we sought to determine whether the administration of cyclosporine at the time of percutaneous coronary intervention (PCI) would limit the size of the infarct during acute myocardial infarction.
  
  
  METHODS
  We randomly assigned 58 patients who presented with acute ST-elevation myocardial infarction to receive either an intravenous bolus of 2.5 mg of cyclosporine per kilogram of body weight (cyclosporine group) or normal saline (control group) immediately before undergoing PCI. Infarct size was assessed in all patients by measuring the release of creatine kinase and troponin I and in a subgroup of 27 patients by performing magnetic resonance imaging (MRI) on day 5 after infarction.
  
  
  RESULTS
  The cyclosporine and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before PCI. The release of creatine kinase was significantly reduced in the cyclosporine group as compared with the control group (P=0.04). The release of troponin I was not significantly reduced (P=0.15). On day 5, the absolute mass of the area of hyperenhancement (i.e., infarcted tissue) on MRI was significantly reduced in the cyclosporine group as compared with the control group, with a median of 37 g (interquartile range, 21 to 51) versus 46 g (interquartile range, 20 to 65; P=0.04). No adverse effects of cyclosporine administration were detected.
  
  
  CONCLUSIONS
  In our small, pilot trial, administration of cyclosporine at the time of reperfusion was associated with a smaller infarct by some measures than that seen with placebo. These data are preliminary and require confirmation in a larger clinical trial.
authors.affiliation: Hôpital Arnaud de Villeneuve, Montpellier, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Piot
authors.forename: Pierre
authors.initials: P
authors.lastname: Croisille
authors.forename: Patrick
authors.initials: P
authors.lastname: Staat
authors.forename: Hélène
authors.initials: H
authors.lastname: Thibault
authors.forename: Gilles
authors.initials: G
authors.lastname: Rioufol
authors.forename: Nathan
authors.initials: N
authors.lastname: Mewton
authors.forename: Rachid
authors.initials: R
authors.lastname: Elbelghiti
authors.forename: Thien Tri
authors.initials: TT
authors.lastname: Cung
authors.forename: Eric
authors.initials: E
authors.lastname: Bonnefoy
authors.forename: Denis
authors.initials: D
authors.lastname: Angoulvant
authors.forename: Christophe
authors.initials: C
authors.lastname: Macia
authors.forename: Franck
authors.initials: F
authors.lastname: Raczka
authors.forename: Catherine
authors.initials: C
authors.lastname: Sportouch
authors.forename: Gerald
authors.initials: G
authors.lastname: Gahide
authors.forename: Gérard
authors.initials: G
authors.lastname: Finet
authors.forename: Xavier
authors.initials: X
authors.lastname: André-Fouët
authors.forename: Didier
authors.initials: D
authors.lastname: Revel
authors.forename: Gilbert
authors.initials: G
authors.lastname: Kirkorian
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Monassier
authors.forename: Geneviève
authors.initials: G
authors.lastname: Derumeaux
authors.forename: Michel
authors.initials: M
authors.lastname: Ovize
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D003131:Combined Modality Therapy; D003402:Creatine Kinase / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010865:Pilot Projects; D011292:Premedication; D016037:Single-Blind Method; D019210:Troponin I / Q000097:blood
chemical_list: D015415:Biomarkers; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019210:Troponin I; D016572:Cyclosporine; D003402:Creatine Kinase