MEASUREMENT OF THE VASOCONSTRICTIVE SUBSTANCES ENDOTHELIN, ANGIOTENSIN-II, AND THROMBOXANE B-2 IN COLD-STORAGE SOLUTION CAN REVEAL PREVIOUSRENAL ISCHEMIC INSULTS

In a rat model, the left kidney was subjected to 60 min of normothermi c ischemia followed by 15 min of reperfusion, whereas the right kidney , serving as a paired control, was not rendered ischemic. Both kidneys were then perfused in situ with either Euro-Collins (EC) solution (n = 12) or University of Wisconsin (UW) solution (n = 6) for 10 min. Eac h kidney was then harvested and stored at 4 degrees C in its respectiv e solution. After 24 and 48 h of cold storage, the following vasoactiv e substances were measured in the preservation media: endothelin (ET), angiotensin II (A-II), thromboxane (B-2) (TxB(2)), and prostaglandin I-2, (PGI(2)). After 24 h in EC solution, left kidneys uniformly produ ced significantly higher concentrations of each vasoactive substance t han right kidneys: ET 1.64+/-0.3 pg/ml vs 0.82+/-0.1 pg/ml (P less tha n or equal to 0.009); A-II 20.8+/-6.2 pg/ml vs 7.75+/-2.3 pg/ml (P les s than or equal to 0.007); TxB(2) 100.8+/-17.7 pg/ml vs 40.1+/-11.7 pg /ml (P less than or equal to 0.04); PGI(2) 638.3+/-41.1 pg/ml vs 318.3 +/-36.4 pg/ml (P less than or equal to 0.001), respectively. At 48 h, a similar pattern of results was obtained as the kidney continued to p roduce TxB(2) and prostacyclins during the 24-48 h period. In the UW s olution, basal levels of ET and A-II were lower than those in EC solut ion, but similarly increased after initial ischemia. At 24 h, the conc entrations produced by the left and right kidneys were as follows: ET 0.66+/-0.1 pg/ml vs 0.48+/-0.1 pg/ml (P less than or equal to 0.14); A -II 10.36+/-3.7 pg/ml vs 2.14+/-0.7 pg/ml(P less than or equal to 0.00 6); TxB(2) 178+/-53 pg/ml vs 52+/-23.1 pg/ml (P less than or equal to 0.001); and PGI(2) 448.3+/-49 pg/ml vs 323+/-44.3 pg/ml (P less than o r equal to 0.01), respectively. After 48 h, the range of concentration s of each substance was similar to that obtained after 24 h. In furthe r studies, the concentrations of ET and A-II were measured in solution previously used to preserve human kidneys (n = 7). The mean concentra tion of ET and A-II in these samples was 3.82+/-1.14 pg/ml and 21.3+/- 9.2 pg/ml, respectively, whereas in control media both substances were below the limits of detection. These results demonstrate that vasocon strictive substances can be measured in the preservation media after a kidney has been stored cold and that higher concentrations are found when the organ has been subjected to prior normothermic ischemia. The measurement of these vasoactive substances before transplantation may reveal that the kidney has been subjected to previous ischemic events. Moreover, these vasoactive substances could be involved in the early recovery of renal function after kidney transplantation.