The vasodilative and anti-cytokine induced cytoprotective effects by inhalative isoflurane on islet engraftment in the liver

H. Yamaya¹, M. Goto², F. Quiang¹, T. Imura², E. Kobayashi³, S. Satomi^1
1 Tohoku university, Adcanced surgery and Technology, Sendai, Japan; ² New Industry Creation Hatchery Center, Tohoku University, Sendai, Japan; ³ Center for Development of Advanced Medical Technology, Jichi Medical University, Shimono, Japan

Objectives: Although animal experiments of islet transplantation are usually performed under some inhalation anesthetics, clinical cases are performed under awake condition. In the present study, we have evaluated the influence of isoflurane on islet engraftment in the liver.

Method: In the rat model, the marginal amounts of syngeneic rat islets were transplanted intraportally into streptozotocin-induced diabetic rats. In the porcine model, autogeneic porcine islets were infused intraportally into the pancreatectomized porcines. In both models, the animals received some islet grafts with and without isoflurane. The blood glucose, the needed amounts of exogenous insulin, glucose tolerance, and the plasma levels of inflammatory cytokines were evaluated. Furthermore, to examine graft location, bioluminescence imaging or venography were used in rat and porcine models, respectively. The morphological evaluation of the transplanted grafts was also performed.

Results: In the rat model, no difference was detected between both groups in terms of the function and location of the transplanted grafts in the liver. On the other hand, in the porcine model, the required amounts of exogenous insulin were significantly lower and the glucose tolerance at 4 weeks after transplantation was considerably ameliorated in the isoflurane group than that in the control group. In porcine plasma analysis, alanine aminotransferase, IL-1 b , and IL -6 were significantly suppressed in isoflurane group. In venography , the middle and left branches of portal veins were still maintained patency in isoflurane group, whereas most radicles were obstructed in the control group. The islet count per liver area was significantly higher in isoflurane group (p<0.0001). The percentage of islets located inside sinusoidal area was also significantly higher in isoflurane group (p<0.0001). The score of inflammatory cell infiltrations to the grafts was significantly lower in isoflurane group (p<0.0001).

Conclusions: These data suggest that anti-inflammatory and vasodilatation effects of isoflurane could synergistically contribute to successful islet engraftment.