EVIDENCE FOR INCREASED NITRIC-OXIDE PRODUCTION AFTER LIVER-TRANSPLANTATION IN HUMANS

To evaluate the role of in vivo-produced nitric oxide (NO) after ortho topic liver transplantation, nitrate, a stable end product of spontane ous NO conversion in blood, was assayed in plasma samples of 32 patien ts, In 31 patients, nitrate increased from 36+/-2 mu M to 137+/-8 mu M within the first 6 postoperative days, In II out of 12 patients with an uneventful early postoperative course, nitrate increased from 33+/- 2 mu M to 70+/-8 mu M, and returned to baseline levels within 2-3 days , In the remaining 20 patients with episodes of rejection and/or infec tion, the nitrate peak was augmented and prolonged, Ten patients suffe ring from these events in the later postoperative course showed a seco nd nitrate elevation, In 31 patients, effective plasma levels of cyclo sporine were reached 4-5 days after OLT, The patient without significa nt elevation in plasma nitrate had effective levels already at day 1, After liver resection or coronary bypass grafting, the median nitrate level remained at 21 mu M (range 15-36 mu M; healthy persons: median 2 4 mu M, range 18-32 mu M). After kidney transplantation nitrate was el evated in the early postoperative course, Thus, NO formation appears t o be increased after solid organ transplantation, but not after other surgeries. After OLT, the increase appears to occur (a) in response to rejection and/or infection, and (b) 4-6 days after surgery in the abs ence of overt complications, In the latter case, NO might be involved in subclinical rejection and its production is possibly dependent upon the effectiveness of the immunosuppressive therapy.