Basis for the preferential activation of cardiac sympathetic nerve activity in heart failure.
In heart failure (HF), sympathetic nerve activity is increased. Measurements in HF patients of cardiac norepinephrine spillover, reflecting cardiac sympathetic nerve activity (CSNA), indicate that it is increased earlier and to a greater extent than sympathetic activity to other organs. This has important consequences because it worsens prognosis, provoking arrhythmias and sudden death. To elucidate the mechanisms responsible for the activation of CSNA in HF, we made simultaneous direct neural recordings of CSNA and renal SNA (RSNA) in two groups of conscious sheep: normal animals and animals in HF induced by chronic, rapid ventricular pacing. In normal animals, the level of activity, measured as burst incidence (bursts of pulse related activity/100 heart beats), was significantly lower for CSNA (30 +/- 5%) than for RSNA (94 +/- 2%). Furthermore, the resting level of CSNA, relative to its maximum achieved while baroreceptors were unloaded by reducing arterial pressure, was set at a much lower percentage than RSNA. In HF, burst incidence of CSNA increased from 30 to 91%, whereas burst incidence of RSNA remained unaltered at 95%. The sensitivity of the control of both CSNA and RSNA by the arterial baroreflex remained unchanged in HF. These data show that, in the normal state, the resting level of CSNA is set at a lower level than RSNA, but in HF, the resting levels of SNA to both organs are close to their maxima. This finding provides an explanation for the preferential increase in cardiac norepinephrine spillover observed in HF.
Ramchandra
Rohit
R
Howard Florey Institute, University of Melbourne, Parkville, Victoria 3010, Australia.
Hood
Sally G
SG
Denton
Derek A
DA
Woods
Robin L
RL
McKinley
Michael J
MJ
McAllen
Robin M
RM
May
Clive N
CN
D000818:Animals; D017704:Baroreflex; D005260:Female; D006321:Heart / Q000294:innervation*; D006333:Heart Failure / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation; D012756:Sheep; D013318:Stroke Volume; D013564:Sympathetic Nervous System / Q000503:physiopathology*