Desmopressin impairs microcirculation in donor pancreas and early graft function after experimental pancreas transplantation.
BACKGROUND
Protective effects of desmopressin in brain dead organ donors oppose reports on a hypercoagulatory potential and an increased leukocyte-endothelial interaction (LEI) after application of the drug. The aim was to evaluate the effect of desmopressin on organ donor's pancreas and early graft function.


METHODS
Donor microcirculation was evaluated via intra-vital microscopy (IVM) in 24 BR (di/di) rats with central diabetes insipidus, randomly assigned to groups I (control without desmopressin application), II (single i.v. application, no pretreatment) or group III (single i.v. desmopressin application, s.c. pretreatment for 3 days). Microcirculation in recipients was evaluated 1 hr and 6 hr after syngenic pancreas transplantation. Groups III and I served as organ donors. After IVM specimens were taken for histology and immunohistochemistry.


RESULTS
Desmopressin in II vs. I led to temporarily (30') increased LEI (Sticker 274.3+/-87.7 vs. 76.5+/-31.1/mm2 endothelial surface; P<0.01) and impaired microcirculation (MCEV 0.43+/-0.07 vs. 0.99+/-0.06 mm/s; P<0.01). Repeated application reduced MCEV and increased LEI for up to 12 hr. Histology in I vs. III showed increased inflammation (n.s.), necrosis (P<0.05) and vacuolization (P<0.01). Immunohistochemistry revealed increased endothelial P-selectin 20' after application. 6 hr after reperfusion organs from III showed reduced MCEV and increased LEI (P<0.01).


CONCLUSIONS
Repeated application of desmopressin impairs graft microcirculation. Perfusion of the pancreas is significantly reduced at the beginning of organ tissue conservation as well as after reperfusion. These disturbances might partly be due to observed endothelial P-selectin expression. Application of desmopressin up to 12 hr prior to organ explantation may impact graft quality.
Keck
T
T
Department of Surgery, University of Heidelberg, Im Neuenheimer Feld 110, 69120 Heidelberg, Germany.
Banafsche
R
R
Werner
J
J
Gebhard
M M
MM
Herfarth
C
C
Klar
E
E
D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D002196:Capillaries / Q000187:drug effects / Q000502:physiology*; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D003919:Diabetes Insipidus / Q000235:genetics / Q000503:physiopathology* / Q000601:surgery; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006400:Hematocrit; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006490:Hemostatics / Q000494:pharmacology*; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008833:Microcirculation / Q000187:drug effects* / Q000502:physiology; D010179:Pancreas / Q000098:blood supply*; D016035:Pancreas Transplantation / Q000379:methods / Q000473:pathology / Q000502:physiology*; D051381:Rats; D011922:Rats, Mutant Strains; D015424:Reperfusion; D014019:Tissue Donors; D014185:Transplantation, Isogeneic; D014699:Venules / Q000187:drug effects / Q000502:physiology
D006490:Hemostatics; D003894:Deamino Arginine Vasopressin