Effects of total body irradiation on the vascular endothelium.

Total body irradiation (TBI) is used as conditioning for stem cell transplantation. We studied its effects on the vascular endothelium in 55 consecutive patients undergoing stem cell transplantation with TBI (TBI group n=35) or without TBI (non-TBI group: n=20). Fifty patients underwent bone marrow transplantation and five underwent peripheral blood stem cell transplantation. The levels of thrombomodulin, plasminogen activator inhibitor-1, and cyclic GMP were measured before and after TBI. At both times, the thrombomodulin and plasminogen activator inhibitor-1 levels were within the normal range in all patients from the two groups, without any significant differences between the groups. The cyclic GMP level was increased after TBI in six of 35 patients. Five of these six patients died as a result of complications of transplantation, while one patient survived in whom the cyclic GMP level rapidly returned to normal. In contrast, the cyclic GMP level remained normal in all patients not receiving TBI. These results suggest that conditioning with TBI stimulates vascular endothelial cells, even if it does not cause immediate direct injury. Such stimulation may be related to vascular endothelial dysfunction, the development of which may be mediated by nitric oxide.