title: The nitric oxide donor, S-nitroso human serum albumin, as an adjunct to HTK-N cardioplegia improves protection during cardioplegic arrest after myocardial infarction in rats.
abstract: OBJECTIVE
  Currently available cardioplegic solutions provide excellent protection in patients with normal surgical risk; in high-risk patients, however, such as in emergency coronary artery bypass surgery, there is still room for improvement. As most of the cardioplegic solutions primarily protect myocytes, the addition of substances for protection of the endothelium might improve their protective potential. The nitric oxide donor, S-nitroso human serum albumin (S-NO-HSA), which has been shown to prevent endothelial nitric oxide synthase uncoupling, was added to the newly developed histidine-tryptophan-ketoglutarat (HTK-N) cardioplegia in an isolated heart perfusion system after subjecting rats to acute myocardial infarction (MI) and reperfusion.
  
  
  METHODS
  In male Sprague-Dawley rats, acute MI was induced by ligation for 1 h of the anterior descending coronary artery. After 2 h of in vivo reperfusion hearts were evaluated on an isolated erythrocyte-perfused working heart model. Cold ischaemia (4°C) for 60 min was followed by 45 min of reperfusion. Cardiac arrest was induced either with HTK (n = 10), HTK-N (n = 10) or HTK-N + S-NO-HSA (n = 10). In one group (HTK-N + S-NO-HSA plus in vivo S-NO-HSA; n = 9) an additional in vivo infusion of S-NO-HSA was performed.
  
  
  RESULTS
  Post-ischaemic recovery of cardiac output (HTK: 77 ± 4%, HTK-N: 86 ± 7%, HTK-N + S-NO-HSA: 101 ± 5%, in vivo S-NO-HSA: 93 ± 8%), external heart work (HTK: 79 ± 5%, HTK-N: 83 ± 3%, HTK-N + S-NO-HSA: 101 ± 8%, in vivo S-NO-HSA: 109 ± 13%), coronary flow (HTK: 77 ± 4%, HTK-N: 94 ± 6%, HTK-N + S-NO-HSA: 118 ± 15%, in vivo S-NO-HSA: 113 ± 3.17%) [HTK-N + S-NO-HSA vs HTK P < 0.001; HTK-N + S-NO-HSA vs HTK-N P < 0.05] and left atrial diastolic pressure (HTK: 122 ± 31%, HTK-N: 159 ± 43%, HTK-N + S-NO-HSA: 88 ± 30, in vivo S-NO-HSA: 62 ± 10%) [HTK-N + S-NO-HSA vs HTK P < 0.05; in vivo S-NO-HSA vs HTK-N P < 0.05] were significantly improved in both S-NO-HSA-treated groups compared with HTK and HTK-N, respectively. This was accompanied by better preservation of high-energy phosphates (adenosine triphosphate; energy charge) and ultrastructural integrity on transmission electron microscopy. However, no additional benefit of in vivo S-NO-HSA infusion was observed.
  
  
  CONCLUSIONS
  Addition of the NO donor, S-NO-HSA refines the concept of HTK-N cardioplegia in improving post-ischaemic myocardial perfusion. HTK-N with S-NO-HSA is a possible therapeutic option for patients who have to be operated on for acute MI.
authors.affiliation: Department of Cardiac Surgery, LK St. Pölten, Pölten, Austria Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna Medical University, Vienna, Austria karola.trescher@meduniwien.ac.at seth.hallstroem@medunigraz.at.
authors.forename: Karola
authors.initials: K
authors.lastname: Trescher
authors.affiliation: Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna Medical University, Vienna, Austria.
authors.forename: Elda
authors.initials: E
authors.lastname: Dzilic
authors.affiliation: Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna Medical University, Vienna, Austria.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Kreibich
authors.affiliation: Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna Medical University, Vienna, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Gasser
authors.affiliation: Department of Pathology, Vienna Medical University, Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Aumayr
authors.affiliation: Department of Pathology, Vienna Medical University, Vienna, Austria.
authors.forename: Dontscho
authors.initials: D
authors.lastname: Kerjaschki
authors.affiliation: Institute of Biophysics, Center of Physiological Medicine, Medical University Graz, Graz, Austria.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pelzmann
authors.affiliation: Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University Graz, Graz, Austria karola.trescher@meduniwien.ac.at seth.hallstroem@medunigraz.at.
authors.forename: Seth
authors.initials: S
authors.lastname: Hallström
authors.affiliation: Department of Cardiac Surgery, LK St. Pölten, Pölten, Austria Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna Medical University, Vienna, Austria.
authors.forename: Bruno K
authors.initials: BK
authors.lastname: Podesser
mesh_terms: D000818:Animals; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D002314:Cardioplegic Solutions / Q000494:pharmacology; D004195:Disease Models, Animal; D005947:Glucose / Q000494:pharmacology; D006323:Heart Arrest / Q000209:etiology / Q000517:prevention & control*; D006324:Heart Arrest, Induced / Q000379:methods*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D009203:Myocardial Infarction / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology*; D011189:Potassium Chloride / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012709:Serum Albumin / Q000494:pharmacology*; D000075462:Serum Albumin, Human; D016896:Treatment Outcome
chemical_list: C039984:Bretschneider cardioplegic solution; D002314:Cardioplegic Solutions; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; C511514:S-nitrosoalbumin, human; D012709:Serum Albumin; D008353:Mannitol; D011343:Procaine; D011189:Potassium Chloride; D005947:Glucose; D000075462:Serum Albumin, Human
keywords: Induced heart arrest; Myocardial infarction; Reperfusion injury