OPPOSING EFFECTS OF PLASMA EPINEPHRINE AND NOREPINEPHRINE ON CORONARY-THROMBOSIS IN-VIVO

Background It is well known that plasma catecholamines and myocardial infarction have a close relation and that coronary artery thrombosis i s a major cause of myocardial infarction. In addition, epinephrine is known to be a prothrombogenic agent in vivo. However, the role of the other major circulating catecholamine, norepinephrine, in the developm ent of coronary thrombosis is somewhat uncertain, although the role of norepinephrine is often considered analogous to the role of epinephri ne. Therefore, the present study was designed to investigate the effec t of norepinephrine and its interaction with epinephrine on coronary t hrombosis. Methods and Results To compare the effects of epinephrine a nd norepinephrine on coronary thrombosis, we analyzed the frequency of cyclic blood flow reductions (CFRs) in an anesthetized canine model o f coronary thrombosis (n=25). Three experiments were used in the prese nt study. In the first experiment with epinephrine infusion, plasma ep inephrine was elevated from 0.46+/-0.25 to 27.7+/-1.85 nmol/L. The fre quency of CFRs increased by more than 60%, from 7.1+/-0.5 to 11.5+/-0. 7 in 40 minutes (P<.01). The second experiment included three experime ntal periods: control, norepinephrine infusion, and norepinephrine inf usion plus epinephrine infusion. Norepinephrine was infused to raise p lasma norepinephrine from 1.3+/-0.2 to 32.4+/-4.3 nmol/L. The frequenc y of CFRs in the dogs was markedly reduced, from 7.89+/-0.42 to 2.41+/ -1.08 in 40 minutes (P<.01), whereas arterial pressure was elevated fr om 88+/-3 to 118+/-5 mm Hg (P<.01). However, when epinephrine infusion was added to the norepinephrine infusion, the frequency of CFRs incre ased from 2.41+/-1.08 to 7.74+/-1.12 in 40 minutes (P<.01). In the thi rd experiment, a servocontrol device was used during the norepinephrin e infusion to prevent rises in coronary arterial pressure. As a result of the norepinephrine infusion, the frequency of CFRs was reduced fro m 7.47+/-0.71 to 0.83+/-0.65 in 40 minutes (P<.01), even though the co ronary arterial pressure was not altered. Conclusions The present stud y demonstrated that infusion of epinephrine stimulated coronary artery thrombosis, whereas infusion of norepinephrine inhibited coronary art ery thrombosis. In addition, the inhibitory effect of norepinephrine o n coronary thrombosis is independent of increases in coronary arterial pressure. Therefore, the present findings suggest that epinephrine an d norepinephrine have opposing effects on coronary thrombosis in dogs.