Johnsson C, Hällgren R, Tufveson G
Departments of Transplantation Surgery and Internal Medicine, University Hospital, Uppsala, Sweden.
J Cardiovasc Pharmacol Ther. 2000 Jul;5(3):229-36. doi: 10.1054/JCPT.8695.
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.
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.
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.
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.
使用透明质酸降解酶——透明质酸酶治疗，可减轻移植器官排斥反应诱导的间质水肿。透明质酸酶还被证明可减少实验性心肌梗死后的组织坏死，但其临床应用因观察到肝素与透明质酸之间的相互作用而受到限制。在本研究中，我们调查了在肝素化动物中是否也能保留该酶的作用。
在异位心脏移植术后第5天，受体大鼠接受2小时的透明质酸酶静脉输注，该酶来源于绵羊或牛。同时，动物接受静脉注射肝素，以2次推注剂量或持续输注方式给药。
两种透明质酸酶制剂均有效降低了排斥反应心脏移植物的透明质酸含量以及含水量。同时使用肝素并未妨碍阳性结果，无论是间歇性给药还是持续给药。
我们在移植模型中的结果清楚地表明，只要给予足够剂量的透明质酸酶，其可成功用于肝素化个体。
