title: S-nitroso human serum albumin attenuates ischemia/reperfusion injury after cardioplegic arrest in isolated rabbit hearts.
abstract: BACKGROUND
  Depletion of nitric oxide (NO) is associated with ischemia/reperfusion injury. The novel NO donor, S-nitroso human serum albumin (S-NO-HSA), could bridge NO depletion during reperfusion in cardiac transplantation and minimize ischemia/reperfusion injury.
  
  
  METHODS
  In an isolated erythrocyte-perfused working heart model, rabbit hearts were randomly assigned after assessment of hemodynamic baseline values to receive S-NO-HSA (0.2 micromol/100 ml, n = 8), L-arginine (10 mmol/100 ml, n = 8) or albumin (control) (0.2 micromol/100 ml, n = 8). After 20 minutes of infusion, the hearts were arrested and stored in Celsior (4 degrees C) enriched with respective drugs for 6 hours, followed by 75 minutes of reperfusion. Hemodynamic values were assessed and biopsy specimens were taken to determine calcium-ionophore stimulated release of NO and superoxide.
  
  
  RESULTS
  During early reperfusion, recovery of cardiac output (75% +/- 6% vs 49% +/- 5%, p < 0.05) and coronary flow (99% +/- 8% vs 70% +/- 5%, p < 0.05) were higher, and myocardial oxygen consumption was reduced in the S-NO-HSA Group compared with Control (4.08 +/- 0.46 ml/min/0.1 kg vs 6.78 +/- 0.38 ml/min/0.1 kg, p < 0.01). At the end of the experiment cardiac output (53% +/- 5% vs 27% +/- 5%, p < 0.01) was higher and left atrial pressure (115% +/- 9% vs 150% +/- 8%, p < 0.05) was lower in the S-NO-HSA Group compared with Control. NO release was increased (1,040 +/- 50 nmol/liter and 1,070 +/- 60 nmol/liter vs 860 +/- 10 nmol/liter, p < 0.01) and superoxide release diminished (31 +/- 5 nmol/liter and 38 +/- 5 nmol/liter vs 64 +/- 5 nmol/liter, p < .01) in the S-NO-HSA and L-arginine Groups compared with Control.
  
  
  CONCLUSIONS
  S-NO-HSA improved hemodynamic functions after prolonged hypothermic cardiac arrest by supplementing NO and thereby decreasing ischemia/reperfusion injury.
authors.affiliation: Ludwig Boltzmann Institute for Cardiosurgical Research at the Institute for Biomedical Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Severin
authors.initials: S
authors.lastname: Semsroth
authors.forename: Barbara
authors.initials: B
authors.lastname: Fellner
authors.forename: Karola
authors.initials: K
authors.lastname: Trescher
authors.forename: Oliver Y
authors.initials: OY
authors.lastname: Bernecker
authors.forename: Leszek
authors.initials: L
authors.lastname: Kalinowski
authors.forename: Harald
authors.initials: H
authors.lastname: Gasser
authors.forename: Seth
authors.initials: S
authors.lastname: Hallström
authors.forename: Tadeusz
authors.initials: T
authors.lastname: Malinski
authors.forename: Bruno K
authors.initials: BK
authors.lastname: Podesser
mesh_terms: D000818:Animals; D002302:Cardiac Output; D050792:Circulatory Arrest, Deep Hypothermia Induced / Q000009:adverse effects; D004727:Endothelium / Q000187:drug effects / Q000502:physiology; D016027:Heart Transplantation; D006439:Hemodynamics / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D009603:Nitroso Compounds / Q000494:pharmacology*; D009926:Organ Preservation / Q000379:methods; D010101:Oxygen Consumption; D011817:Rabbits; D015427:Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control*; D012709:Serum Albumin / Q000494:pharmacology*; D000075462:Serum Albumin, Human
chemical_list: D009603:Nitroso Compounds; C511514:S-nitrosoalbumin, human; D012709:Serum Albumin; D009569:Nitric Oxide; D000075462:Serum Albumin, Human