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Biomedical Engineers should
never go it alone. I have benefited tremendously from long-standing, strong
collaborations with several laboratories across the nation. My life science
colleagues bring me back to reality when I go off into the analytical and
technical ether, as engineers are so apt to do (we can’t help ourselves, it’s
a design feature!). Collectively we have worked together to understand the
cellular mechanisms of baroreflex function. |
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Neural control
of the circulation in vertebrates is regulated by numerous hormonal and
neuronal reflexes. The most well studied, and arguably the most important of
these mechanisms are the arterial baroreceptor reflexes (baroreflexes), which
are the first to respond to arterial pressure changes. Over a normal range of
arterial pressure variations (eg. 80-120 mmHg for humans), the baroreflexes
maintain cardiovascular homeostasis (ie. the most appropriate pressure
setpoint and cardiac output for the current physiological conditions).
However, in response to perturbations away from this setpoint, this system
exerts a rapid and very potent neural drive in an effort to return arterial
pressure back to within acceptable operating conditions. As a result, the
baroreflexes play an essential role in the overall control of the
cardiovascular system through the regulation of heart rate, strength of
contraction (contractility) and vasomotor tone. |
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The
baroreceptor reflex is initiated by stretch receptors (ie. baroreceptors or pressoreceptors)
located in the walls of the large systemic arteries, the two primary
baroreceptor areas being the aortic arch and carotid sinus. These structures
encode arterial pressure (P), as well as its derivative (dP/dt), into a
frequency-modulated train of action potentials that is transmitted along
sensory fibers to the medullary portion of the brainstem where projections of
baroreceptor afferents (sensory fibers) terminate on secondary neurons within
the nucleus tractus solitarius (NTS). Located in the dorsomedial region of
the medulla oblongata, the NTS is a complex integrative zone which receives a
wide variety of neural information. In addition to contributing to autonomic
control of cardiac activity, the NTS also processes sensory signals from gastrointestinal,
respiratory and trigeminal (facial afferent [1]) sources as well as receiving
numerous projections from higher nervous centers (eg. regions of the
hypothalamus, parabrachialis and area postrema), all of which have been shown
to influence baroreflex activity.[2,3] Our attention is focused however, on
the characterization of only the aortic and carotid sinus baroreceptor inputs
to the NTS, specifically examining the dynamic properties of these inputs and
their modulatory effects on heart rate. The major afferent pathways
associated with aortic arch and carotid sinus baroreceptors are the Xth (ie.
vagus) and IXth (ie. glossopharyngeal) cranial nerves, respectively. In
mammals, afferent aortic baroreceptor fibers form a common nerve bundle termed
the aortic depressor nerve (ADN) before joining up with the vagus. In rat,
the ADN contains purely aortic baroreceptor fibers.[4]
Morphological studies using the ADN have demonstrated that the majority of
aortic nerve fibers terminate in a relatively restricted region within the
medial area of the nucleus of the tractus solitarius (mNTS).[5,6] Both
baroreceptor and chemoreceptor (chemical sensing) terminals exit the carotid
sinus region to form the carotid sinus nerve (CSN) or Herring's nerve, prior
to joining the glossopharyngeal nerve. Unfortunately, no counterpart to the
ADN exists for the CSN and therefore it is not possible to clearly
distinguish between baroreceptor and chemoreceptor afferent fibers. However,
it has been demonstrated that a significant portion of carotid sinus
afferents (ie. both baroreceptors and chemoreceptors) terminate within the
NTS [7,8,9] and that in the rat [10] these
terminations are most dense in the ipsilateral mNTS. Neural control of the
heart is often described in terms of the relative contributions of the
sympathetic and parasympathetic components of the autonomic nervous system.
Sympathetic drive involves a spinally descending pathway with projections to
the intermediolateral cell column (IML) of preganglionic sympathetic neurons,
which are the final common pathway of the central nervous system in
sympathetic control of the cardiovascular system.[11]
The origins and neural activity of these descending fibers is not yet well
characterized, further complicating the neuroanatomical description of the
sympathetic aspect of the cardiovascular system. A much clear understanding
exists for parasympathetic nervous outflow to the heart which is carried via
cardiac motor (efferent) fibers located in the vagus. The origins
of cardiac vagal preganglionic fibers in rat has been well
characterized using both anatomical and electrophysiological techniques. [12,13] These studies have demonstrated that the vagus nerve
receives medullary projections from both the dorsal motor nucleus of X (DMN)
and the nucleus ambiguus (NA). However, the major vagal myocardial
projections effecting heart rate originate in the rostral portion of the
NA.[14] Pathways through the central nervous system taken by second-order
neurons associated with the baroreflex are in the process of being
classified. [2,15,16] In addition, the manner in which sensory information
from the carotid sinus and aortic arch baroreceptors is integrated within the
mNTS and further processed by neurons within the NA, is not clearly understood
and requires further study. Nonetheless, it is widely accepted that the mNTS
and NA comprise a significant portion of the medullary vasomotor and cardiac
control circuitry. [2] The extent and character of the communicative pathways
between these two medullary regions is not well understood. However, there is
a strong body of evidence suggesting that the essential neural circuitry
associated with the baroreflex, as it contributes to basal (ie.
parasympathetic and sympathetic) control of cardiac function, is comprised of
a serial sequence of only a few neurons (ie. oligosynaptic). [17,11,15,10,12,7] In fact, Stuesse and Fish (1984) have
presented experimental evidence suggesting: ``There is only one major
projection to the rostral nucleus ambiguus: the medial nucleus of the
solitary tract.'' Such detailed electrophysiological and anatomical studies
of the neural structures associated with the baroreflex has led Seiders and
Stuesse (1984) to conclude: ``Thus the simplest baroreceptor pathway would
involve two central nervous system synapses and consist of CSN afferents to
mNTS, mNTS to nucleus ambiguus, and nucleus ambiguus to the heart.'' We
contend a similar approximation can be made for the aortic portion of the
baroreflex. |
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