title: Cardioprotective effects of low-dose cyclosporin A added to histidine-tryptophan-ketoglutarate cardioplegia solution prior to total myocardial ischemia: an in vitro rabbit heart study.
abstract: OBJECTIVE
  Mitochondrial permeability transition pore (MPTP) opening appears to play a key role in myocardial cell survival after ischemia-reperfusion injury and can be inhibited by cyclosporin A (CsA). We investigated whether low-dose CsA added to histidine-tryptophan-ketoglutarate (HTK) cardioplegia solution could improve myocardial protection during longer periods of global myocardial ischemia as encountered during cardiac surgery.
  
  
  METHODS
  Rabbit hearts perfused on a Langendorff apparatus were arrested with cold HTK solution containing 1 μmol/l CsA. After 90 min of ischemia, the hearts were reperfused and pmax, max dp/dt, min dp/dt, myocardial stiffness, pO(2), coronary flow and heart rate recorded. Tissue ATP and malondialdehyde (MDA) were measured to assess cell energy content and oxidative stress, respectively.
  
  
  RESULTS
  CsA-treated hearts recovered pmax (p = 0.026), max dp/dt (p = 0.028) and min dp/dt (p = 0.025) more quickly and to a greater extent than non-treated hearts. They required markedly less oxygen (p = 0.041) in the first 10 min of reperfusion. Hearts treated with CsA produced 44% less MDA (1.09 vs. 1.93, p = 0.008), while ATP levels were unchanged.
  
  
  CONCLUSIONS
  HTK cardioplegia solution containing CsA at a dose well below that expected to cause systemic immunosuppressive effects leads to a significant and timelier recovery of myocardial contractility, while consuming less oxygen.
authors.affiliation: Heart Centre Leipzig, Leipzig, Germany. patp_s@yahoo.com.au
authors.forename: P
authors.initials: P
authors.lastname: Pritzwald-Stegmann
authors.forename: A
authors.initials: A
authors.lastname: Hoyer
authors.forename: J
authors.initials: J
authors.lastname: Kempfert
authors.forename: S
authors.initials: S
authors.lastname: Dhein
authors.forename: F W
authors.initials: FW
authors.lastname: Mohr
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002314:Cardioplegic Solutions / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D016572:Cyclosporine / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D008353:Mannitol / Q000494:pharmacology; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D010100:Oxygen / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D011817:Rabbits; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: C039984:Bretschneider cardioplegic solution; D002314:Cardioplegic Solutions; D002316:Cardiotonic Agents; D007166:Immunosuppressive Agents; D008353:Mannitol; D008315:Malondialdehyde; D011343:Procaine; D011189:Potassium Chloride; D016572:Cyclosporine; D000255:Adenosine Triphosphate; D005947:Glucose; D010100:Oxygen