title: Tetrahydrobiopterin improves cardiac and pulmonary function after cardiopulmonary bypass.
abstract: OBJECTIVE
  Tetrahydrobiopterin (BH4) is an important cofactor of endogenous nitric oxide synthesis. In the present preclinical study, we investigated the effects of BH4 on cardiac and pulmonary function during early reperfusion in an experimental model of cardioplegic arrest and extracorporal circulation.
  
  
  METHODS
  Twelve anesthetized dogs underwent hypothermic cardiopulmonary bypass. After 60 min of hypothermic cardiac arrest, reperfusion was started after application of either saline vehicle (control, n = 6), or BH4 (n = 6). Left-ventricular end-systolic pressure volume relationship (E(es)) was measured by a combined pressure-volume conductance catheter at baseline and after 60 min of reperfusion. Left anterior descending (LAD) coronary (CBF) and pulmonary blood flow (PBF), endothelium-dependent vasodilatation to acetylcholine (ACh), endothelium-independent vasodilatation to sodium nitroprusside (SNP) and alveolo-arterial O₂ gradient were determined.
  
  
  RESULTS
  The administration of BH4 led to a significantly better recovery of E(es) (given as percent of baseline: 85 ± 22 vs 46 ± 15%, p<0.05). CBF was also significantly higher in the BH4 group (38 ± 5 vs 22 ± 5 ml min⁻¹, p<0.05). While the vasodilatatory response to SNP was similar in both groups, injection of ACh resulted in a significantly higher increase in CBF (64 ± 12 vs 25 ± 12%, p < 0.05) and PBF (49 ± 15 vs 36 ± 14%, p<0.05) in the BH4-treated animals. Alveolo-arterial O₂ gradient was significantly lower after BH4 supplementation (80 ± 15 vs 49 ± 14 mm Hg, p < 0.05).
  
  
  CONCLUSIONS
  Application of BH4 improves myocardial, endothelial and pulmonary function after cardiopulmonary bypass with hypothermic cardiac arrest. The observed protective effects indicate that BH4 could be a novel therapeutic option in the treatment of ischemia/reperfusion injury.
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany.
authors.forename: Gábor
authors.initials: G
authors.lastname: Szabó
authors.forename: Leila
authors.initials: L
authors.lastname: Seres
authors.forename: Pál
authors.initials: P
authors.lastname: Soós
authors.forename: Matthias
authors.initials: M
authors.lastname: Gorenflo
authors.forename: Béla
authors.initials: B
authors.lastname: Merkely
authors.forename: Ferenc
authors.initials: F
authors.lastname: Horkay
authors.forename: Matthias
authors.initials: M
authors.lastname: Karck
authors.forename: Tamás
authors.initials: T
authors.lastname: Radovits
mesh_terms: D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002315:Cardiopulmonary Bypass / Q000009:adverse effects* / Q000379:methods; D003326:Coronary Circulation / Q000187:drug effects; D006152:Cyclic GMP / Q000097:blood; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006324:Heart Arrest, Induced / Q000009:adverse effects; D006439:Hemodynamics / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D010100:Oxygen / Q000097:blood; D011182:Postoperative Care / Q000379:methods*; D014664:Vasodilation / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D001708:Biopterins; C003402:sapropterin; D006152:Cyclic GMP; D010100:Oxygen