NORADRENALINE BIOSYNTHESIS AND METABOLISM DURING DEVELOPMENT AND RECOVERY FROM PACING-INDUCED HEART-FAILURE IN THE DOG

We have modified an assay utilizing ion-pair high-performance liquid c hromatography with electrochemical detection to measure dihydroxypheny lalanine and dyhydroxyphenylglycol simultaneously with noradrenaline. We measured these agents at control, 1 and 3 weeks following the onset of rapid ventricular pacing, as well as 4 weeks after the cessation o f a 3-week period of pacing. Our findings were as follows. Plasma nora drenaline increased significantly at 1 week and increased further afte r 3 weeks of pacing (control, 202 +/- 16; 1 week, 528 +/- 62; 3 weeks, 750 +/- 139 pg . mL-1). Plasma dihydroxyphenylalanine did not change throughout, while plasma dihydroxyphenylglycol was significantly eleva ted at 3 weeks (513 +/- 48 vs. 388 +/- 35 pg . mL-1 for the control). Four weeks after discontinuation of pacing, all parameters did not dif fer from the control. These results imply that during the development of heart failure, the rise in circulating noradrenaline does not refle ct simply an increase in catecholamine synthesis, but that there are m ore dynamic changes associated with noradrenaline spill-over, uptake, and metabolism.