Oxidized glutathione as a marker of ischemia reperfusion associated with single lung transplantation.

Abstract

Previous data have shown that glutathione (GSH), an endogenous antioxidant, is converted to its oxidized form (GSSG) after oxidative ischemia-reperfusion events. As GSSG is toxic to cells and is extruded through an active mechanism dependent on intracellular GSSG levels, substance appears in plasma. Single lung transplantation was performed upon 18 puppies, 3 to 5 kg, with a two hour ischemic time for the donor lung before reimplantation. Recipient animal plasma was obtained after anesthesia induction, pulmonary artery ligation, recipient pneumonectomy, reestablishment of blood flow to the donor lung, completion of transplant, and one, two, and three hours postoperatively. Donor lung bronchoalveolar lavage fluid (BALF) was obtained at the time of harvest, after perfusion of the donor lung with EuroCollins, immediately pretransplant, and after completion of the vascular anastomoses. Oxidized and total GSH levels in plasma and BALF samples were determined by a spectrophotometric assay. After reimplantation of the ischemic donor lung, there was a statistically significant increase in both GSSG and GSH in plasma samples, and a statistically significant increase in GSSG in the BALF. Compartmental differences between arterial and venous plasma, as well as the increase in GSSG in the BALF, implicated the lung that was transplanted as the source of oxygen free radical generation and GSSG release. Plasma GSSG levels seem to provide a sensitive, noninvasive, repeatable measure of ongoing tissue response and oxygen free radical production.