Tetrahydrobiopterin attenuates microvascular reperfusion injury following murine pancreas transplantation

M. Maglione, M. Hermann, P. Hengster, S. Schneeberger, W. Mark, P. Obrist, G. Werner-Felmayer, E. R. Werner, R. Margreiter, G. Brandacher

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


In this study we investigated the effect of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthases, on ischemia-reperfusion injury (IRI) following murine pancreas transplantation. Pancreatic grafts were exposed to prolonged cold ischemia times (CIT) and different treatment regimens: normal saline (S), S + 16 h CIT, BH4 50 mg/kg + 16 h CIT. Nontransplanted animals served as controls. Graft microcirculation was analyzed by means of functional capillary density (FCD) and capillary diameters (CD) after 2 h reperfusion using intravital microscopy. Quantification of inflammatory responses (mononuclear infiltration) and endothelial disintegration (edema formation) was done by histology (hematoxylin and eosin), and peroxynitrite formation assessed by nitrotyrosine immunostaining. FCD was significantly reduced after prolonged CIT, paralleled by increased peroxynitrite formation as compared with controls (all p < 0.05). Microcirculatory changes correlated significantly with intragraft peroxynitrite generation (Spearman: r = -0.56; p < 0.01). Pancreatic grafts treated with BH4 displayed markedly higher FCD values (p < 0.01) and abrogated nitrotyrosine staining (p = 0.03). CD were not significantly different in any group. Histology showed increased inflammation, interstitial edema, hemorrhage, acinar vacuolization and focal areas of necrosis after 16 h CIT, which was diminished by BH4 administration (p < 0.01). BH4 treatment significantly reduces post-ischemic deterioration of microcirculation as well as histologic damage and might be a promising novel strategy in attenuating IRI following pancreas transplantation.

Original languageEnglish (US)
Pages (from-to)1551-1559
Number of pages9
JournalAmerican Journal of Transplantation
Issue number7
StatePublished - Jul 2006
Externally publishedYes


  • Graft pancreatitis
  • Ischemia-reperfusion injury
  • Microvascular injury
  • Nitric oxide synthase
  • Pancreas transplantation

ASJC Scopus subject areas

  • Immunology and Allergy
  • Transplantation
  • Pharmacology (medical)


Dive into the research topics of 'Tetrahydrobiopterin attenuates microvascular reperfusion injury following murine pancreas transplantation'. Together they form a unique fingerprint.

Cite this