Mechanisms underlying the increased cardiac norepinephrine spillover in heart failure
Journal Publication ResearchOnline@JCUAbstract
Patients with heart failure (HF) have increased levels of cardiac norepinephrine (NE) spillover, which is an independent predictor of mortality. We hypothesized that this increase in NE spillover in HF depends not only on increases in sympathetic nerve activity (SNA) but also on changes in the mechanisms controlling NE release and reuptake. Such changes would lead to differences between the increases in directly recorded SNA and NE spillover to the heart in HF. Experiments were conducted in conscious sheep implanted with electrodes to record cardiac SNA (CSNA). In addition, arterial pressure and cardiac NE spillover were determined. In HF, the levels of both CSNA (102 ± 8 vs. 45 ± 8 bursts/min, P < 0.05) and cardiac NE spillover (21.6 ± 3.8 vs. 3.9 ± 0.8 pmol/min, P < 0.05) were significantly higher than in normal control animals. In HF, baroreflex control of cardiac NE spillover was impaired, and when CSNA was abolished by increasing arterial pressure, there was no reduction in cardiac NE spillover. A decrease in cardiac filling pressures in the HF group led to a significant increase in CSNA, but it significantly decreased cardiac NE spillover. In HF, the levels of cardiac NE spillover were enhanced above those expected from the high level of SNA, suggesting that changes in mechanisms controlling NE release and reuptake further increase the high level of NE at the heart, which will act to enhance the deleterious effects of increased CSNA in HF.
Journal
American Journal of Physiology-Heart and Circulatory Physiology
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N/A
Volume
315
ISBN/ISSN
1522-1539
Edition
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Issue
2
Pages Count
8
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Publisher
American Physiological Society
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EISSN
N/A
DOI
10.1152/ajpheart.00069.2018