Effect of donor treatment with heparinoids on graft function after intraportal transplantation of a marginal islet mass: an experimental study.
Heparinoids interact with factors that are involved in ischemia-reperfusion injury and thus may prevent organ injury. We therefore studied the effects on subsequent intraportal islet transplantation of systemic administration of unfractionated and N-desulphated heparin to donors prior to pancreatectomy. Donor rats were given an intravenous injection of either heparin (1.3 mg/kg or 13.3 mg/kg; 200 U/kg or 2000 U/kg, respectively) or N-desulphated heparin (50 mg/kg; approximately 5 U/kg) at 5 to 10 minutes prior to pancreas procurement. Five hundred freshly isolated islets were injected intraportally into syngeneic male Lewis recipients that had developed streptozotocin-induced diabetes. Blood glucose and body weight were monitored for 5 weeks thereafter. Rats transplanted with islets from donors given high dose heparin showed a fall in blood glucose from 25.1 +/- 1.4 to 11.0 +/- 2.7 mmol/L (P <.01) with 60% of animals euglycemic within the first week. In contrast, the controls, did not show a fall in glucose levels at 1 week and none had become euglycaemic. Normalization of glycemia was slower in recipients of islets from animals treated with the lower dose of heparin. Results were intermediate with islets from donors given N-desulphated heparin. Nevertheless, all heparinoids used in this study caused more than a doubling of the number of animals achieving normoglycemia by 3 to 4 weeks. We hypothesize that pretreatment of the donor with heparin protects islet integrity during procurement and isolation and hence accelerates islet engraftment and remodelling. Since the effect was seen with N-desulphated heparin, which has negligible anticoagulant properties, we believe the mechanism to be independent of the anticoagulant activity.
Juszczak
M T
MT
Department of Endocrinology and Diabetes, Royal Free Campus, University College London, London, UK. juszczak@rfc.ucl.ac.uk
Hughes
S J
SJ
Jones
G L
GL
Powis
S H
SH
Press
M
M
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000601:surgery*; D004195:Disease Models, Animal; D006496:Heparinoids / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000166:cytology; D016381:Islets of Langerhans Transplantation / Q000379:methods* / Q000502:physiology; D008297:Male; D011169:Portal Vein; D051381:Rats; D011917:Rats, Inbred Lew; D012016:Reference Values
D000925:Anticoagulants; D001786:Blood Glucose; D006496:Heparinoids