title: Custodiol-N, the novel cardioplegic solution reduces ischemia/reperfusion injury after cardiopulmonary bypass.
abstract: BACKGROUND
  On the basis of Custodiol preservation and cardioplegic solution a novel cardioplegic solution was developed to improve the postischemic cardiac and endothelial function. In this study, we investigated whether its reduced cytotoxicity and its ability to reduce reactive oxygen species generation during hypoxic condition have beneficial effects in a clinically relevant canine model of CPB.
  
  
  METHODS
  12 dogs underwent cardiopulmonary bypass with 60 minutes of hypothermic cardiac arrest. Dogs were divided into 2 groups: Custodiol (n = 6) and Custodiol-N (n = 6) (addition of L-arginin, N-α-acetyl-L-histidine and iron-chelators: deferoxamine and LK-614). Left ventricular hemodynamic variables were measured by a combined pressure-volume conductance catheter at baseline and after 60 minutes of reperfusion. Coronary blood flow, myocardial ATP content, plasma nitrate/nitrite and plasma myeloperoxidase levels were also determined.
  
  
  RESULTS
  The use of Custodiol-N cardioplegic solution improved coronary blood flow (58 ± 7 ml/min vs. 26 ± 3 ml/min) and effectively prevented cardiac dysfunction after cardiac arrest. In addition, the myocardial ATP content (12,8 ± 1,0 μmol/g dry weight vs. 9,5 ± 1,5 μmol/g dry weight) and plasma nitrite (1,1 ± 0,3 ng/ml vs. 0,5 ± 0,2 ng/ml) were significantly higher after application of the new cardioplegic solution. Furthermore, plasma myeloperoxidase level (3,4 ± 0,4 ng/ml vs. 4,3 ± 2,2 ng/ml) significantly decreased in Custodiol-N group.
  
  
  CONCLUSIONS
  The new HTK cardioplegic solution (Custodiol-N) improved myocardial and endothelial function after cardiopulmonary bypass with hypothermic cardiac arrest. The observed protective effects imply that the Custodiol-N could be the next generation cardioplegic solution in the protection against ischemia-reperfusion injury in cardiac surgery.
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. gaborveres@yahoo.com.|Heart and Vascular Center, Semmelweis University, Budapest, Hungary. gaborveres@yahoo.com.
authors.forename: Gábor
authors.initials: G
authors.lastname: Veres
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. radovitstamas@yahoo.com.|Heart and Vascular Center, Semmelweis University, Budapest, Hungary. radovitstamas@yahoo.com.
authors.forename: Tamás
authors.initials: T
authors.lastname: Radovits
authors.affiliation: Heart and Vascular Center, Semmelweis University, Budapest, Hungary. bela.merkely@kardio.sote.hu.
authors.forename: Béla
authors.initials: B
authors.lastname: Merkely
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. matthias.karck@med.uni-heidelberg.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Karck
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. szabog69@gmail.com.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
mesh_terms: D000818:Animals; D002314:Cardioplegic Solutions / Q000494:pharmacology / Q000627:therapeutic use*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004730:Endothelium, Vascular / Q000503:physiopathology; D006324:Heart Arrest, Induced / Q000379:methods; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D019188:Organ Preservation Solutions / Q000494:pharmacology / Q000627:therapeutic use*; D017382:Reactive Oxygen Species / Q000097:blood; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
chemical_list: D002314:Cardioplegic Solutions; C549285:Custodiol-N solution; D019188:Organ Preservation Solutions; D017382:Reactive Oxygen Species