MYOCARDIAL FATTY-ACID METABOLISM DURING ACUTE CARDIAC ALLOGRAFT-REJECTION

Fatty acids are promptly taken up, metabolised and eliminated by healt hy cardiomyocytes. Cardiomyopathy, coronary heart disease and chronic rejection are known to be associated with an impaired fatty acid metab olism. It was the aim of this study to investigate fatty acid metaboli sm in a rat heart transplant model and to correlate scintigraphic find ings with histological changes. After right-side nephrectomy of Lewis recipients Brown Norway cardiac allografts were anastomosed to the ren al vessels. Animals were given no immunosuppression. The metabolism of carrier-free 17-(123)jodo-heptadecanoic acid ((123)J-HDA) with a spec ific activity of >2X10(17) Bq/ml was scintigraphically measured betwee n days 1 and 11. An increase in the grade of rejection was observed ov er time. Fifty-six frames of 30 s duration each were recorded. For the region of interest (native heart, transplanted heart, left kidney) fr ames 10-56 were superimposed, time-activity curves generated and monoe xponentially fitted. Furthermore, elimination half-life and intercepts were calculated. Following scintigraphic evaluation the animals were killed and graft as well as native hearts excised for histological exa mination. The uptake of the tracer identified severe grades of rejecti on. Elimination half-life of the tracer was twice as long from hearts with mild rejection and more than 14 times as long in severe rejection compared with no rejection. Elimination half-life and amplitude did n ot permit discrimination between grades 1, 2 and 3 a, but significantl y decreased in groups 3 b and 4. This method therefore seems to be a v aluable tool for the noninvasive detection of severe acute cardiac all ograft rejection. Since fatty acid metabolism is clearly stress-depend ent it remains to be seen whether this method allows detection of earl ier rejection in loaded hearts.