H Lin1, D B Young. 1. Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505.
Abstract
BACKGROUND: It is well known that plasma catecholamines and myocardial infarction have a close relation and that coronary artery thrombosis is 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 development of coronary thrombosis is somewhat uncertain, although the role of norepinephrine is often considered analogous to the role of epinephrine. Therefore, the present study was designed to investigate the effect of norepinephrine and its interaction with epinephrine on coronary thrombosis. METHODS AND RESULTS: To compare the effects of epinephrine and norepinephrine on coronary thrombosis, we analyzed the frequency of cyclic blood flow reductions (CFRs) in an anesthetized canine model of coronary thrombosis (n = 25). Three experiments were used in the present study. In the first experiment with epinephrine infusion, plasma epinephrine was elevated from 0.46 +/- 0.25 to 27.7 +/- 1.85 nmol/L. The frequency 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 experimental periods: control, norepinephrine infusion, and norepinephrine infusion plus epinephrine infusion. Norepinephrine was infused to raise plasma norepinephrine from 1.3 +/- 0.2 to 32.4 +/- 4.3 nmol/L. The frequency 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 from 88 +/- 3 to 118 +/- 5 mm Hg (P < .01). However, when epinephrine infusion was added to the norepinephrine infusion, the frequency of CFRs increased from 2.41 +/- 1.08 to 7.74 +/- 1.12 in 40 minutes (P < .01). In the third experiment, a servocontrol device was used during the norepinephrine infusion to prevent rises in coronary arterial pressure. As a result of the norepinephrine infusion, the frequency of CFRs was reduced from 7.47 +/- 0.71 to 0.83 +/- 0.65 in 40 minutes (P < .01), even though the coronary arterial pressure was not altered. CONCLUSIONS: The present study demonstrated that infusion of epinephrine stimulated coronary artery thrombosis, whereas infusion of norepinephrine inhibited coronary artery thrombosis. In addition, the inhibitory effect of norepinephrine on coronary thrombosis is independent of increases in coronary arterial pressure. Therefore, the present findings suggest that epinephrine and norepinephrine have opposing effects on coronary thrombosis in dogs.
BACKGROUND: It is well known that plasma catecholamines and myocardial infarction have a close relation and that coronary artery thrombosis is 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 development of coronary thrombosis is somewhat uncertain, although the role of norepinephrine is often considered analogous to the role of epinephrine. Therefore, the present study was designed to investigate the effect of norepinephrine and its interaction with epinephrine on coronary thrombosis. METHODS AND RESULTS: To compare the effects of epinephrine and norepinephrine on coronary thrombosis, we analyzed the frequency of cyclic blood flow reductions (CFRs) in an anesthetized canine model of coronary thrombosis (n = 25). Three experiments were used in the present study. In the first experiment with epinephrine infusion, plasma epinephrine was elevated from 0.46 +/- 0.25 to 27.7 +/- 1.85 nmol/L. The frequency 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 experimental periods: control, norepinephrine infusion, and norepinephrine infusion plus epinephrine infusion. Norepinephrine was infused to raise plasma norepinephrine from 1.3 +/- 0.2 to 32.4 +/- 4.3 nmol/L. The frequency 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 from 88 +/- 3 to 118 +/- 5 mm Hg (P < .01). However, when epinephrine infusion was added to the norepinephrine infusion, the frequency of CFRs increased from 2.41 +/- 1.08 to 7.74 +/- 1.12 in 40 minutes (P < .01). In the third experiment, a servocontrol device was used during the norepinephrine infusion to prevent rises in coronary arterial pressure. As a result of the norepinephrine infusion, the frequency of CFRs was reduced from 7.47 +/- 0.71 to 0.83 +/- 0.65 in 40 minutes (P < .01), even though the coronary arterial pressure was not altered. CONCLUSIONS: The present study demonstrated that infusion of epinephrine stimulated coronary artery thrombosis, whereas infusion of norepinephrine inhibited coronary artery thrombosis. In addition, the inhibitory effect of norepinephrine on coronary thrombosis is independent of increases in coronary arterial pressure. Therefore, the present findings suggest that epinephrine and norepinephrine have opposing effects on coronary thrombosis in dogs.
Authors: Frank A J L Scheer; Kun Hu; Heather Evoniuk; Erin E Kelly; Atul Malhotra; Michael F Hilton; Steven A Shea Journal: Proc Natl Acad Sci U S A Date: 2010-11-08 Impact factor: 11.205
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