title: Peroxynitrite, the breakdown product of nitric oxide, is beneficial in blood cardioplegia but injurious in crystalloid cardioplegia.
abstract: BACKGROUND
  Peroxynitrite (ONOO(-)) has been implicated as a primary mediator in the deleterious effects of nitric oxide (NO) in crystalloid solutions, possibly due to a lack of detoxification mechanisms, leading to the formation of.OH. In contrast, ONOO(-) may exert cardioprotective effects in blood environments secondary to detoxification and the subsequent formation of NO-donating nitrosothiols. This dichotomy in physiological effects of ONOO(-) may exist between crystalloid and blood cardioplegia (BCP) environments. In the present study, we tested the hypothesis that ONOO(-) is cardiotoxic in crystalloid cardioplegia but cardioprotective in BCP in ischemically injured hearts.
  
  
  RESULTS
  In anesthetized dogs on cardiopulmonary bypass, global 37 degrees C ischemia was imposed for 30 minutes, followed by 60 minutes of intermittent 4 degrees C hyperkalemic crystalloid (Plegisol) or BCP with (+) or without (-) 5 micromol/L authentic ONOO(-). After 2 hours of reperfusion, left ventricular (LV) function (end-systolic pressure-volume relations, in percent of baseline) was 56+/-3% in Plegisol-, which was further reduced in Plegisol+ to 40+/-4%.* In contrast, postischemic systolic function was better in BCP+ groups than in BCP- groups (96+/-2%* versus 82+/-2%, respectively). Differences in functional recovery could not be attributed to differences in hemodynamics. LV end-diastolic stiffness was significantly increased with the addition of ONOO(-) in both Plegisol (298+/-26% versus 466+/-30%*) and BCP (201+/-22% versus 267+/-13%*) groups. Consistent with increased LV chamber stiffness, myocardial edema was increased in BCP+ compared with BCP- (78.9+/-0.3% versus 76.4+/-0.3%*) and in Plegisol+ compared with Plegisol- (81.1+/-0.3% versus 79.6+/-0.4%*). Creatine kinase activity was significantly increased in Plegisol+ (48+/-6) compared with that in Plegisol- (31+/-6) but was unchanged in BCP- (14+/-2) relative to BCP+ (18+/-1). Nitrotyrosine (ng/mg protein) accumulation in LV myocardial biopsy samples confirmed myocardial exposure to ONOO(-) or its metabolites (Plegisol- 1.2+/-0.1, Plegisol+ 3.31+/-0.3*, BCP- 1.4+/-0.2, BCP+ 2.9+/-0.2*).
  
  
  CONCLUSIONS
  We conclude that (1) the postcardioplegic cardiodynamic effects of ONOO(-) depend on its environment and (2) ONOO(-) in crystalloid solution impairs postcardioplegia systolic and diastolic functional recovery, whereas (3) ONOO(-) in BCP increases functional recovery. This environment-dependent dichotomy in the effect of ONOO(-) may affect the benefits of NO-related adjuncts to crystalloid or BCP solutions (*P<0.05 versus group without ONOO(-)). :II-384-II-391.)
authors.affiliation: Cardiothoracic Research Laboratory, Division of Cardiothoracic Surgery, Department of Surgery, Emory University School of Medicine, Carlyle Fraser Heart Center of Crawford Long Hospital and Emory University, Atlanta, GA 30365-2225, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Ronson
authors.forename: V H
authors.initials: VH
authors.lastname: Thourani
authors.forename: X L
authors.initials: XL
authors.lastname: Ma
authors.forename: S L
authors.initials: SL
authors.lastname: Katzmark
authors.forename: D
authors.initials: D
authors.lastname: Han
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Zhao
authors.forename: M
authors.initials: M
authors.lastname: Nakamura
authors.forename: R A
authors.initials: RA
authors.lastname: Guyton
authors.forename: J
authors.initials: J
authors.lastname: Vinten-Johansen
mesh_terms: D000818:Animals; D002315:Cardiopulmonary Bypass; D004285:Dogs; D006324:Heart Arrest, Induced / Q000379:methods; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D009566:Nitrates / Q000008:administration & dosage*; D009569:Nitric Oxide; D016877:Oxidants / Q000008:administration & dosage*
chemical_list: D009566:Nitrates; D016877:Oxidants; C039642:peroxynitric acid; D009569:Nitric Oxide