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 chromatography with electrochemical detection to measure dihydroxyphenylalanine 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 of a 3-week period of pacing. Our findings were as follows. Plasma noradrenaline increased significantly at 1 week and increased further after 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 elevated at 3 weeks (513 +/- 48 vs. 388 +/- 35 pg . mL-1 for the control). Four weeks after discontinuation of pacing, all parameters did not differ from the control. These results imply that during the development of heart failure, the rise in circulating noradrenaline does not reflect simply an increase in catecholamine synthesis, but that there are more dynamic changes associated with noradrenaline spill-over, uptake, and metabolism.