Carbon monoxide, a highly toxic gas often called the "silent killer," may prove useful for extending the life of transplanted organs, suggests a University of Pittsburgh study that found prolonged, low-dose exposure to be protective against chronic rejection in a rat kidney transplant model. Chronic rejection is the primary reason that patients require second or third transplant operations.

In the study, to be published in an upcoming issue of the American Journal of Physiology-Renal Physiology and available now as an online publication, the researchers report minimal signs of inflammation and tissue damage indicative of chronic rejection following kidney transplantation in rats housed for 30 days in cages with air consisting of 20 parts per million of carbon dioxide. In contrast, the kidneys transplanted into rats maintained in normal air conditions began to deteriorate almost immediately, and microscopic examination revealed progressive rejection. Both groups were given a six-day course of the anti-rejection drug tacrolimus.

Although carbon monoxide is toxic at high concentrations, at low concentrations it appears to function as a signaling molecule that protects cells against bombardment by the inflammatory immune response, says senior author Noriko Murase, M.D., associate professor of surgery at the Thomas E. Starzl Transplantation Institute, University of Pittsburgh School of Medicine. The idea to study the effects of carbon monoxide in the transplant setting came from co-author Augustine Choi, M.D., professor of medicine and chief of the division of pulmonary, allergy, and critical care medicine, who is a leading expert on the effects of carbon monoxide.

University of Pittsburgh Schools of the Health Sciences researchers are frequent contributors to peer-reviewed journals and presenters at scientific meetings, reporting on a wide range of basic science and clinical research findings. The following provides a brief overview of some of the discoveries recently reported by Pitt faculty.

Jim Swyers
Lisa Rossi
University of Pittsburgh Medical Center

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