INCREASED SERUM NITRATE CONCENTRATION IN CARDIAC TRANSPLANT PATIENTS - A MARKER FOR ACUTE ALLOGRAFT CELLULAR REJECTION

The purpose of the present study was to investigate whether nitrate se rum level, reflecting total body production of nitric oxide in vivo, c ould serve as a noninvasive marker for acute human cardiac rejection. Serum nitrate concentration was determined by an enzymatic method, Dur ing routine right ventricular endomyocardial biopsies in 59 recipients , 145 tissue samples were obtained. Two groups of biopsy specimen were considered on the basis of posttransplant delay: group 1, less than o r equal to 90 days (n=47; 12-90 days); and group 2, >90 days (n=98; 3- 81 months). All patients had normal ventricular systolic function on t he day of biopsy and none had evidence of infection. Rejection grade c orrelated closely with serum nitrate concentration (P<0.001). In both groups, nitrate serum concentrations differed significantly (P<0.001) among cases without rejection, those with mild ongoing rejection (grad e 1A/1B), and those with focal or diffuse aggressive infiltrates (grad e 2 or higher). A cutoff value of 20 mu mol/L was determined that was positively predictive for grade 2 or higher rejection in 62% cases of early episodes of rejection and in 68% cases of late rejection, Conver sely, a serum nitrate level below 20 mu mol/L was negatively predictiv e in 97% and 94% of early and late cases, respectively, We conclude th at the acute rejection process of the human transplanted heart is acco mpanied by a significant increase in serum nitrate level, reflecting i ncreased nitric oxide production during the immune response. Because o f its high negative predictive value, irrespective of the posttranspla ntation delay, nitrate serum determination may have clinical utility i n the noninvasive monitoring of the cardiac transplant patient and cou ld also add important information to endomyocardial biopsy analysis fo r treatment decision making.