title: Addition of vardenafil into storage solution protects the endothelium in a hypoxia-reoxygenation model.
abstract: OBJECTIVE
  Based upon the well known protective effect of intracellular cyclic guanosine monophosphate (cGMP) accumulation, we tested the hypothesis that storage solution enriched with optimal concentration of the phosphodiestherase-5 inhibitor vardenafil could provide better protection of vascular grafts against reperfusion injury after long-term cold ischaemic storage.
  
  
  METHODS
  Isolated thoracic aorta obtained from rats underwent 24-h cold ischaemic preservation in physiological saline or vardenafil (10(-11) M)-supplemented saline solution. Reperfusion injury was simulated by hypochlorite (200 μM) exposure for 30 minutes. Endothelium-dependent vasorelaxation was assessed, and histopathological and molecular-biological examination of the aortic tissue were performed.
  
  
  RESULTS
  Compared with the control group, the saline group showed significantly attenuated endothelium-dependent maximal relaxation (Rmax) to acetylcholine after hypoxia-reoxygenation, which was significantly improved by vardenafil supplementation (Rmax control: 98 ± 1%; saline: 48 ± 6%; vardenafil: 75 ± 4%; p < .05). Vardenafil treatment significantly reduced DNA strand breaks (control: 10.6 ± 6.2%; saline: 72.5 ± 4.0%; vardenafil: 14.2 ± 5.2%; p < .05) and increased cGMP score in the aortic wall (control: 8.2 ± 0.6; saline: 4.5 ± 0.3; vardenafil: 6.7 ± 0.6; p < .05).
  
  
  CONCLUSIONS
  Our results support the view that impairment of intracellular cGMP signalling plays a role in the pathogenesis of the endothelial dysfunction induced by cold storage warm reperfusion, which can be effectively reversed by pharmacological phosphodiesterase-5 inhibition.
authors.affiliation: Department of Cardiac Surgery, University of Heidelberg, Heidelberg, Germany. gaborveres@yahoo.com
authors.forename: G
authors.initials: G
authors.lastname: Veres
authors.forename: P
authors.initials: P
authors.lastname: Hegedűs
authors.forename: E
authors.initials: E
authors.lastname: Barnucz
authors.forename: R
authors.initials: R
authors.lastname: Zöller
authors.forename: T
authors.initials: T
authors.lastname: Radovits
authors.forename: S
authors.initials: S
authors.lastname: Korkmaz
authors.forename: F
authors.initials: F
authors.lastname: Kolonics
authors.forename: A
authors.initials: A
authors.lastname: Weymann
authors.forename: M
authors.initials: M
authors.lastname: Karck
authors.forename: G
authors.initials: G
authors.lastname: Szabó
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation; D017209:Apoptosis / Q000187:drug effects; D050377:Cold Ischemia; D006152:Cyclic GMP / Q000378:metabolism; D019610:Cytoprotection; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000637:transplantation; D005786:Gene Expression Regulation / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D058986:Phosphodiesterase 5 Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D013450:Sulfones / Q000494:pharmacology; D013997:Time Factors; D014227:Triazines / Q000494:pharmacology; D000069058:Vardenafil Dihydrochloride; D058017:Vascular Grafting / Q000009:adverse effects; D057772:Vascular System Injuries / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D007093:Imidazoles; D019188:Organ Preservation Solutions; D058986:Phosphodiesterase 5 Inhibitors; D010879:Piperazines; D013450:Sulfones; D014227:Triazines; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000069058:Vardenafil Dihydrochloride; D006152:Cyclic GMP
keywords: Endothelium; Ischaemia-reperfusion injury; Storage; Vardenafil; cGMP