CARDIAC AND ARTERIAL BAROREFLEXES IN HEART FAILURE

The studies proposed in this application are designed to answer a
variety of questions relating to the neural control of the
cardiovascular system in the disease state of congestive heart
failure. We will determine if abnormalities in carotid sinus
baroreceptor discharge exist in dogs with two models of low
output heart failure (pulmonary artery stenosis plus tricuspid
avulsion and chronic tachycardia) compared to sham operated
animals. Single units from carotid sinus nerve will be recorded in
these experiments. In addition, measurement of carotid sinus
volume and diameter will be done in order to assess changes in
compliance. In companion studies, the isolated carotid sinus
technique will be used to look at the carotid sinus reflex control
of the peripheral vasculature in as quantitative a manner as is
possible in conscious dogs with and without heart failure. The
baroreflex control of renal sympathetic nerve activity will also be
investigated in conscious dogs with heart failure. The isolated
carotid sinus technique will allow local perfusion of the carotid
sinuses so that the effects of agents such as cardiac glycosides
can be studied without complicating the experiments with their
systemic effects. In subsequent studies, the role of cardiac
receptor stimulation on the baroreflex control of regional
resistances and sympathetic nerve activity will be studied to
determine if input from these receptors (atrial and ventricular)
alter the baroreflex in heart failure. In addition, the effects of
selective cardiac receptor stimulation on sympathetic nerve
activity will be assessed in dogs with chronic heart failure.
Finally, in order to test the hypothesis that the salt and water
retention of heart failure is mediated, in part, by exaggerated
tubular responses to renal nerve activity, dogs with and without
heart failure will be subjected to low level renal nerve stimulation
or to reflex activation of renal sympathetic nerves while
measuring salt and water excretion as well as GFR and renal
blood flow. These studies will be carried out in the basal state
and during plasma volume expansion in order to augment sodium
excretion. In addition, the effects of bilateral renal denervation
on renal function will be investigated in dogs with heart failure.
This 5-year program represents a multidisciplinary approach to
investigate the reflex abnormalities which may contribute to the
symptomatology of chronic heart failure.