Hyaluronidase can be used to reduce interstitial edema in the presence of heparin.
BACKGROUND
Treatment with the hyaluronan-degrading enzyme, hyaluronidase, reduces rejection-induced interstitial edema of transplanted organs. Hyaluronidase has also been demonstrated to reduce tissue necrosis after experimentally induced myocardial infarction, but its clinical use has been limited by an observed interaction between heparin and hyaluronan. In the present work, we investigated whether it is also possible to retain the effect of the enzyme in heparinized animals.


METHODS
Day 5 after heterotopic heart transplantation, recipient rats received a 2-hour intravenous infusion of hyaluronidase, either of ovine or of bovine origin. Concomitantly, the animals received intravenous heparin, either as 2 bolus doses or as a constant infusion.


RESULTS
Both hyaluronidase preparations effective reduced the hyaluronan content as well as the water content of the rejecting cardiac grafts. The concomitant use of heparin did not hamper the positive results, neither when heparin was administered intermittently nor when it was given continuously.


CONCLUSIONS
Our results in the transplantation model clearly demonstrate that hyaluronidase can be successfully used in heparinized individuals, provided that sufficient doses of the enzyme are given.
Johnsson
C
C
Departments of Transplantation Surgery and Internal Medicine, University Hospital, Uppsala, Sweden.
Hällgren
R
R
Tufveson
G
G
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use; D001760:Bleeding Time; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D002417:Cattle; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D006084:Graft Rejection / Q000150:complications / Q000188:drug therapy; D016027:Heart Transplantation; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use; D006820:Hyaluronic Acid / Q000378:metabolism*; D006821:Hyaluronoglucosaminidase / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011921:Rats, Inbred WKY
D000925:Anticoagulants; D006820:Hyaluronic Acid; D006493:Heparin; D006821:Hyaluronoglucosaminidase