scholarly journals Increased cardiac sympathetic nerve activity in heart failure is not due to desensitization of the arterial baroreflex

2007 ◽  
Vol 293 (1) ◽  
pp. H798-H804 ◽  
Author(s):  
A. M. D. Watson ◽  
S. G. Hood ◽  
R. Ramchandra ◽  
R. M. McAllen ◽  
C. N. May
Keyword(s):  
Heart Failure ◽  
Heart Rate ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Cardiac Sympathetic Nerve ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
Maximum Gain ◽  
Arterial Baroreceptors ◽  
Cardiac Sympathetic Nerve Activity

Increased sympathetic drive to the heart worsens prognosis in heart failure, but the level of cardiac sympathetic nerve activity (CSNA) has been assessed only by indirect methods, which do not permit testing of whether its control by arterial baroreceptors is defective. To do this, CSNA was measured directly in 16 female sheep, 8 of which had been ventricularly paced at 200–220 beats/min for 4–6 wk, until their ejection fraction fell to between 35 and 40%. Recording electrodes were surgically implanted in the cardiac sympathetic nerves, and after 3 days' recovery the responses to intravenous phenylephrine and nitroprusside infusions were measured in conscious sheep. Electrophysiological recordings showed that resting CSNA (bursts/100 heartbeats) was significantly elevated in heart-failure sheep (89 ± 3) compared with normal animals (46 ± 6; P < 0.001). This increased CSNA was not accompanied by any increase in the low-frequency power of heart-rate variability. The baroreceptor-heart rate reflex was significantly depressed in heart failure (maximum gain −3.29 ± 0.56 vs. −5.34 ± 0.66 beats·min−1·mmHg−1 in normal animals), confirming published findings. In contrast, the baroreflex control of CSNA was undiminished (maximum gain in heart failure −6.33 ± 1.06 vs. −6.03 ± 0.95%max/mmHg in normal sheep). Direct recordings in a sheep model of heart failure thus show that resting CSNA is strikingly increased, but this is not due to defective control by arterial baroreceptors.

scholarly journals Mechanisms underlying the increased cardiac norepinephrine spillover in heart failure

2018 ◽  
Vol 315 (2) ◽  
pp. H340-H347 ◽  
Author(s):  
Rohit Ramchandra ◽  
Sally G. Hood ◽  
Daniel Xing ◽  
Gavin W. Lambert ◽  
Clive N. May
Keyword(s):  
Heart Failure ◽  
Arterial Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Cardiac Sympathetic Nerve ◽  
Nerve Activity ◽  
Baroreflex Control ◽  
Cardiac Sympathetic Nerve Activity ◽  
Conscious Sheep ◽  
High Level

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. NEW & NOTEWORTHY This is the first study, to our knowledge, to compare direct recordings of cardiac sympathetic nerve activity with simultaneously measured cardiac norepinephrine (NE) spillover. Our results indicate that in heart failure, increased cardiac sympathetic nerve activity is a major contributor to the increased NE spillover. In addition, there is enhanced NE spillover for the levels of synaptic nerve activity.

scholarly journals Adrenomedullin increases cardiac sympathetic nerve activity in normal conscious sheep

2005 ◽  
Vol 187 (2) ◽  
pp. 275-281 ◽  
Author(s):  
C J Charles ◽  
D L Jardine ◽  
M G Nicholls ◽  
A M Richards
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Vehicle Control ◽  
Cardiac Sympathetic Nerve ◽  
Burst Frequency ◽  
Nerve Activity ◽  
Cardiac Sympathetic Nerve Activity ◽  
Conscious Sheep

The sympathetic nervous system and adrenomedullin (AM) both participate in the regulation of cardiac and circulatory function but their interaction remains uncertain. We have examined the effects of AM on cardiac sympathetic nerve activity (CSNA) and hemodynamics and contrasted these effects with pressure-matched nitro-prusside (NP) administration in normal conscious sheep. Compared with vehicle control, arterial pressure fell similarly with AM (P=0.04) and NP (P<0.001). Heart rate rose in response to both AM (P<0.001) and NP (P=0.002) but the rise with AM was significantly greater than that induced by NP (P<0.001). Cardiac output increased in response to AM compared with both control and NP (both P<0.001). CSNA burst frequency (bursts/min) were increased in response to both AM (P<0.001) and NP (P=0.005) with the rise in burst frequency being greater with AM compared with NP (P<0.001). CSNA burst area/min was also raised by both AM (P=0.03) and NP (P=0.002) with a trend for burst area being greater with AM than NP (P=0.07). CSNA burst incidence (bursts/100 beats) showed no significant differences between any treatment day. In conclusion, we have demonstrated that AM is associated with a greater increase in CSNA and heart rate for a given change in arterial pressure than seen with the classic balanced vasodilator NP.

Stimulation of cardiac sympathetic nerve activity by central angiotensinergic mechanisms in conscious sheep

2004 ◽  
Vol 286 (6) ◽  
pp. R1051-R1056 ◽  
Author(s):  
Anna M. D. Watson ◽  
Rasim Mogulkoc ◽  
Robin M. McAllen ◽  
Clive N. May
Keyword(s):  
Heart Rate ◽  
Arterial Pressure ◽  
Hypertonic Saline ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Ang Ii ◽  
Cardiac Sympathetic Nerve ◽  
Nerve Activity ◽  
Cardiac Sympathetic Nerve Activity ◽  
Conscious Sheep

Central actions of angiotensin play an important role in cardiovascular control and have been implicated in the pathogenesis of hypertension and heart failure. One feature of centrally or peripherally administered angiotensin is that the bradycardia in response to an acute pressor effect is blunted. It is unknown whether after central angiotensin this is due partly to increased cardiac sympathetic nerve activity (CSNA). We recorded CSNA and arterial pressure in conscious sheep, at least 3 days after electrode implantation. The effects of intracerebroventricular infusions of ANG II (3 nmol/h for 30 min) and artificial cerebrospinal fluid (CSF) (1 ml/h) were determined. The response to intracerebroventricular hypertonic saline (0.6 M NaCl in CSF at 1 ml/h) was examined as there is evidence that hypertonic saline acts via angiotensinergic pathways. Intracerebroventricular angiotensin increased CSNA by 23 ± 7% ( P < 0.001) and mean arterial pressure (MAP) by 7.6 ± 1.2 mmHg ( P < 0.001) but did not significantly change heart rate ( n = 5). During intracerebroventricular ANG II the reflex relation between CSNA and diastolic blood pressure was significantly shifted to the right ( P < 0.01). Intracerebroventricular hypertonic saline increased CSNA (+9.4 ± 6.6%, P < 0.05) and MAP but did not alter heart rate. The responses to angiotensin and hypertonic saline were prevented by intracerebroventricular losartan (1 mg/h). In conclusion, in conscious sheep angiotensin acts within the brain to increase CSNA, despite increased MAP. The increase in CSNA may account partly for the lack of bradycardia in response to the increased arterial pressure. The responses to angiotensin and hypertonic saline were losartan sensitive, indicating they were mediated by angiotensin AT-1 receptors.

Changes in AdSNA and arterial catecholamines to coronary occlusion in cats

1988 ◽  
Vol 255 (4) ◽  
pp. H704-H710 ◽  
Author(s):  
T. Honda ◽  
I. Ninomiya
Keyword(s):  
Heart Rate ◽  
Sympathetic Nerve ◽  
Sympathetic Nerve Activity ◽  
Coronary Occlusion ◽  
The Other ◽  
Cardiac Sympathetic Nerve ◽  
Nerve Activity ◽  
Control Value ◽  
Cardiac Sympathetic Nerve Activity ◽  
The Relationship

The relationship between adrenal (preganglionic) sympathetic nerve activity (AdSNA), cardiac sympathetic nerve activity (CSNA), and arterial catecholamines, i.e., epinephrine (Epi) and norepinephrine (NE), were analyzed during 200 s of occlusion of left anterior descending coronary artery in anesthetized cats. With coronary occlusion, AdSNA maximally increased to 168 +/- 20% (mean +/- SE) of the control value at 20 s and gradually decreased to 149 +/- 10% at 200 s. Mean CSNA (MCSNA), mean arterial pressure, and heart rate decreased significantly because of coronary occlusion. Arterial NE and Epi progressively increased from 0.54 +/- 0.05 and 0.29 +/- 0.03 ng/ml to 1.41 +/- 0.16 and 0.59 +/- 0.08 ng/ml at 3 min after the onset of occlusion, respectively. The correlation between AdSNA and arterial Epi (r = 0.71; P less than 0.01) and between AdSNA and arterial NE (r = 0.57; P less than 0.05) were significant, but the correlation between CSNA and arterial NE was not significant. On the other hand, in adrenalectomized cats, the increases in arterial Epi and NE did not appear during coronary occlusion. We concluded that, with coronary occlusion, AdSNA increased and, in turn, caused an increase in arterial Epi and NE.

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