Responses of cardiac sympathetic nerve activity to changes in circulating volume differ in normal and heart failure sheep

Abstract

Factors controlling cardiac sympathetic nerve activity (CSNA) in the normal state and those causing the large increase in activity in heart failure (HF) remain unclear. We hypothesized from previous clinical findings that activation of cardiac mechanoreceptors by the increased blood volume in HF may stimulate sympathetic nerve activity (SNA), particularly to the heart via cardiocardiac reflexes. To investigate the effect of volume expansion and depletion on CSNA we have made multiunit recordings of CSNA in conscious normal sheep and sheep paced into HF. In HF sheep (n = 9) compared with normal sheep (n = 9), resting levels of CSNA were significantly higher (34 +/- 5 vs. 93 +/- 2 bursts/100 heart beats, P < 0.05), mean arterial pressure was lower (76 +/- 3 vs. 87 +/- 2 mmHg; P < 0.05), and central venous pressure (CVP) was greater (3.0 +/- 1.0 vs. 0.0 +/- 1.0 mmHg; P < 0.05). In normal sheep (n = 6), hemorrhage (400 ml over 30 min) was associated with a significant increase in CSNA (179 +/- 16%) with a decrease in CVP (2.7 +/- 0.7 mmHg). Volume expansion (400 ml Gelofusine over 30 min) significantly decreased CSNA (35 +/- 12%) and increased CVP (4.7 +/- 1.0 mmHg). In HF sheep (n = 6) the responses of CSNA to both volume expansion and hemorrhage were severely blunted with no significant changes in CSNA or heart rate with either stimulus. In summary, these studies in a large conscious mammal demonstrate that in the normal state directly recorded CSNA increased with volume depletion and decreased with volume loading. In contrast, both of these responses were severely blunted in HF with no significant changes in CSNA during either hemorrhage or volume expansion.

Stimulation of the cardiopulmonary baroreflex enhances ventricular contractility in awake dogs: a mathematical analysis study

“…However, our result conflicts with the experimental study of Ramchandra et al (24), in which cardiac sympathetic nerve activity decreased with increasing CVP during blood volume changes in conscious sheep. The opposing result may be due to the presence of confounding physiological mechanisms (e.g., arterial baroreflex) in their study and possibly species differences.…”

“…Experimentally, previous studies have produced conflicting results. Ramchandra et al (24) showed that cardiac sympathetic nerve activity changes in the opposite direction of CVP in conscious sheep during blood volume changes. By contrast, Karim et al (10) demonstrated that cardiac sympathetic nerve activity increases, while renal sympathetic nerve activity decreases, in response to stimulation of the cardiopulmonary baroreflex via left atrial balloon distension in anesthetized dogs.…”

Discharge properties of cardiac and renal sympathetic nerves and their impaired responses to changes in blood volume in heart failure

“…In this context, we recently demonstrated inhibition of cardiac SNA (CSNA) during volume expansion and stimulation of CSNA during hemorrhage (31); however, whether this occurs due to selective changes in cardiac sympathetic burst amplitude is unknown.…”

Central exogenous nitric oxide decreases cardiac sympathetic drive and improves baroreflex control of heart rate in ovine heart failure

“…The accuracy of burst determination was checked by eye over the 5-min control data for each sheep. We have demonstrated previously that this method gives similar results to integration and rectification of the sympathetic signal (34).…”

“…Anesthesia was induced with intravenous sodium thiopental (15 mg/kg), and following intubation, it was maintained with 1.5-2.0% isoflurane/O 2. In the first surgery, all sheep were prepared with a carotid arterial loop and in the sheep; to be paced into heart failure, a pacing lead was inserted into the right ventricle under fluoroscopic guidance (34,39). In the second surgery, lateral ventricle guide tubes were implanted under anesthesia (24).…”