Evidence for increased nitric oxide production after liver transplantation in humans

To evaluate the role of in vivo-produced nitric oxide (NO) after orthotopic liver transplantation, nitrate, a stable end product of spontaneous NO conversion in blood, was assayed in plasma samples of 32 patients. In 31 patients, nitrate increased from 36 +/- 2 microM to 137 +/- 8 microM within the first 6 postoperative days. In 11 out of 12 patients with an uneventful early postoperative course, nitrate increased from 33 +/- 2 microM to 70 +/- 8 microM, and returned to baseline levels within 2-3 days. In the remaining 20 patients with episodes of rejection and/or infection, the nitrate peak was augmented and prolonged. Ten patients suffering from these events in the later postoperative course showed a second nitrate elevation. In 31 patients, effective plasma levels of cyclosporine were reached 4-5 days after OLT. The patient without significant 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 microM (range 15-36 microM; healthy persons: median 24 microM, range 18-32 microM). After kidney transplantation nitrate was elevated in the early postoperative course. Thus, NO formation appears to 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 absence 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.