Hyaluronidase ameliorates rejection-induced edema

Hyaluronan, a glucosaminoglycan with unique water-binding capacity, is accu mulated in the interstitial edematous tissue in rejecting organs. We here i nvestigated whether the increased tissue content of water and hyaluronan se en during allograft rejection can be prevented by treatment with the hyalur onan-degrading enzyme hyaluronidase. Heterotopic heart transplantations bet ween PVG and Wistar/Kyoto rats were performed. Recipient rats were treated with hyaluronidase prophylactically or therapeutically, either alone or in combination with cyclosporine. Daily intravenous injections of hyaluronidas e induced a significant reduction of the cardiac content of both hyaluronan and water, as evaluated on day six after transplantation. Morphological ex amination revealed grafts with better preserved morphology and fewer infilt rating mononuclear cells, compared to untreated controls. Hyaluronidase the rapy, alone or combined with cyclosporine, resulted in prolonged graft surv ival times. Hyaluronidase infusion for two hours also reduced already estab lished edema five days after transplantation. This study confirms the hypot hesis that hyaluronan accumulation plays a critical role in edema formation , and that hyaluronidase therapy can be used to reduce edema after organ tr ansplantation.