Edema treatment during cardiac allograft rejection

Interstitial edema of rejecting organs can be correlated with the accumulation of hyaluronan in the transplant; since hyaluronan has strong water-binding capacity, treatment with the hyaluronan-degrading enzyme hyaluronidase reduces not only the hyaluronan content but also the water content of the graft. The aim of the present study was to investigate whether a further reduction of the water content would be the result if hyaluronidase was used in conjunction with classic diuretic substances.

Five days after heterotopic heart transplantation (PVG to Wistar/Kyoto), recipient rats received hyaluronidase as a continuous intravenous infusion over 2 hours together with either a loop-diuretic (furosemide) or an osmotic diuretic (mannitol).

Hyaluronidase was found to reduce the hyaluronan contents of the grafts from 586+/-52 microg/g in control animals receiving vehicle infusion to 161+/-48 microg/g (p < 0.001) and the water contents from 81.3+/-0.4 x 10(-2) U to 79.7+/-0.4 x 10(-2) U (p < 0.05). Combined treatment with furosemide or mannitol did not affect the results and neither furosemide nor mannitol had any intrinsic capacity to affect the water or hyaluronan contents of the cardiac grafts.

This experiment confirms our previous findings of hyaluronidase as an effective edema-reducing drug and indicate that no additive effect is obtained by a combined therapy with diuretics and hyaluronidase.