ArticleAnnals of surgery2003
Endothelin(A) receptor blockade reduces ischemia/reperfusion injury in pig pancreas transplantation.
Article in Annals of surgery, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed, 35 citations in OpenAlex.
- Dynamic Nomogram for Predicting Thrombocytopenia in Adults with Acute Pancreatitis.Journal of inflammation research · 2021Article
- Melatonin role preventing steatohepatitis and improving liver transplantation results.Cellular and molecular life sciences : CMLS · 2016Review
- Interleukin-17 expression in murine pressure ulcer tissues.Experimental and therapeutic medicine · 2013Article
- Altered cellular membrane fluidity levels and lipid peroxidation during experimental pancreas transplantation.Journal of bioenergetics and biomembranes · 2012Article
- Repeated gene transfection impairs the engraftment of transplanted porcine neonatal pancreatic cells.Diabetes & metabolism journal · 2011Article
- The endothelin/nitric oxide balance determines small-for-size liver injury after reduced-size rat liver transplantation.Virchows Archiv : an international journal of pathology · 2005Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveThe effect of prophylactic administration of a selective endothelin(A) receptor antagonist (ET(A)-RA) on ischemia/reperfusion injury in an experimental model of graft pancreatitis after pancreas transplantation was evaluated. SUMMARY BACKGROUND DATA: It is well established that endothelin-1 (ET-1), a powerful vasoconstrictor, plays an important role in the development of pancreatitis. Recent studies have shown a beneficial effect of endothelin receptor antagonists in the therapy for experimental pancreatitis.
methodsRelevant ischemia/reperfusion injury was induced in pig pancreas transplants after 6 hours hypothermic preservation in University of Wisconsin solution. The recipients were randomized into 2 groups: control pigs received isotonic saline and the treated group received the selective ET(A)-RA BSF 208075 at the beginning of reperfusion. On postoperative days 2 and 5, animals were relaparotomized to obtain tissue specimens. Blood monitoring included lipase, amylase, C-reactive protein, trypsinogen-activation peptide, thiobarbituric acid-reacting substances, and ET-1. Partial oxygen tension (p(ti)O(2)) was measured by a Clarke-type electrode and blood flow by laser doppler. A semiquantitative score index was used for assessment of histologic injury and for immunohistochemical analysis of ET-1 and ET(A) receptor expression. Tissue mRNA levels of prepro ET-1, ET(A) receptor, pro-interleukin (IL)-6, and pro-IL-1beta were quantified using TaqMan real-time reverse transcription-polymerase chain reaction (RT-PCR).
resultsProphylactic treatment with ET(A)-RA significantly reduced the severity of graft pancreatitis evidenced by C-reactive protein. The finding of transient capillary perfusion at the beginning of reperfusion supports the application of the ET(A)-RA during this period. The dramatic increase of plasma ET-1 in the therapy group is a clear evidence of effective receptor blockade. Mean trypsinogen-activation peptide levels from the portal venous effluent, but not mean systemic plasma TAP values were significantly lower in the treated group. Analysis of p(ti)O(2) and blood flow revealed a significant improvement of capillary perfusion and blood flow in the treated group and was associated with relevant reduction of tissue injury. Intrapancreatic ET-1 and IL-6 mRNA expression and ET-1 protein levels were significantly lower in the therapy group as compared with the control group. In contrast, ET(A) mRNA showed a marked up-regulation by ET(A) receptor blockade.
conclusionApplication of a ET(A)-RA reduces ischemia/reperfusion induced graft pancreatitis in a pig transplantation model by improving microcirculation and reducing tissue injury.
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