title: Leukocyte-depleted terminal blood cardioplegia provides superior myocardial protective effects in association with myocardium-derived nitric oxide and peroxynitrite production for patients undergoing prolonged aortic crossclamping for more than 120 minutes.
abstract: OBJECTIVE
  This study was designed to examine the myocardial protective effect of leukocyte-depleted terminal blood cardioplegia in association with nitric oxide and peroxynitrite production, especially for patients undergoing prolonged aortic crossclamping.
  
  
  METHODS
  Fifty-four patients (34 men, 20 women, mean age 56.7 +/- 12.7 years) undergoing aortic valve replacement were randomly allocated to one of two groups; group LDTC (n = 27) received 10 minutes of leukocyte-depleted terminal blood cardioplegic solution, and group CONT (n = 27) served as controls. Each group was subdivided into 2 groups: aortic crossclamping for less than 120 minutes in groups LDTC-S (n = 13) and CONT-S (n = 14); aortic crossclamping for 120 minutes or more in groups LDTC-L (n = 14) and CONT-L (n = 13).
  
  
  RESULTS
  After aortic unclamping, group LDTC-L showed higher incidence of spontaneous defibrillation (78.6% vs 30.8%, P =.0213), higher plasma nitrate + nitrite in the coronary sinus effluent (32.5 +/- 4.1 vs 28.7 +/- 3.0 micromol/L, P =.0013), lower differences between coronary sinus effluent and arterial blood in the percentage ratio of nitrotyrosine to tyrosine (myocardium-derived peroxynitrite; 2.987% +/- 0.576% vs 3.951% +/- 0.952%, P =.0036), and plasma polymorphonuclear-elastase (113.9 +/- 21.3 vs 155.5 +/- 41.6 microg/L, P =.0029) and malondialdehyde (2.75 +/- 0.67 vs 4.02 +/- 0.96 micromol/L, P =.0005) than group CONT did. Postoperatively, group LDTC-L showed lower human-heart fatty acid-binding protein (111.4 +/- 25.2 vs 156.4 +/- 38.6 IU/L, P =.0013), lower creatine kinase-muscle and brain (19.2 +/- 4.7 vs 24.8 +/- 6.5 IU/L, P =.0120), and smaller requirement of catecholamine (5.44 +/- 2.29 vs 8.45 +/- 3.42 microg x kg(-1) x min(-1), P =.0122). There were no significant differences in these parameters between groups LDTC-S and CONT-S.
  
  
  CONCLUSIONS
  This study demonstrated that leukocyte-depleted terminal blood cardioplegia provided superior myocardial protective effects and regulated myocardial-derived nitric oxide and peroxynitrite production only for patients undergoing aortic crossclamping for more than 120 minutes. The results suggest that prolonged aortic crossclamping deteriorates the tolerance to leukocyte-mediated myocardial injury accompanied by endothelial dysfunction associated with nitric oxide and peroxynitrite production.
authors.affiliation: Department of Surgery, Course of Interventional Medicine (E1), Osaka University Graduate School of Medicine, Suita, Japan. hayashi@surg1.med.osaka-u.ac.jp
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
authors.forename: Naoto
authors.initials: N
authors.lastname: Fukuyama
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Toshiki
authors.initials: T
authors.lastname: Takahashi
authors.forename: Hiroe
authors.initials: H
authors.lastname: Nakazawa
authors.forename: Hikaru
authors.initials: H
authors.lastname: Matsuda
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001011:Aorta / Q000502:physiology*; D001021:Aortic Valve / Q000601:surgery*; D001769:Blood; D002314:Cardioplegic Solutions; D003250:Constriction; D005260:Female; D006324:Heart Arrest, Induced / Q000379:methods; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007937:Leukapheresis; D019272:Leukocyte Elastase / Q000097:blood; D008297:Male; D008875:Middle Aged; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism*; D009504:Neutrophils / Q000502:physiology; D009569:Nitric Oxide / Q000096:biosynthesis*; D030421:Peroxynitrous Acid / Q000096:biosynthesis*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D002314:Cardioplegic Solutions; D018836:Inflammation Mediators; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D019272:Leukocyte Elastase