During sympathetic stimulation, nerve terminals take up around 70% of the norepinephrine released. The remaining norepinephrine is carried away by the bloodstream. These processes are slow. The facilitatory effects of sympathetic stimulation on the heart take longer to reach steady-state values compared to the inhibitory effects of vagal stimulation. The onset of the cardiac response to sympathetic stimulation is slow due to the slow release of norepinephrine from sympathetic nerve terminals. Additionally, the cardiac effects of neurally released norepinephrine are mainly mediated by a relatively slow second messenger system involving cyclic adenosine monophosphate (cAMP). Therefore, sympathetic activity has a slower impact on heart rate and AV conduction compared to vagal activity. Vagal activity can exert beat-by-beat control over cardiac function, while sympathetic activity cannot.

Cardiac rate, rhythm, and contractility can be significantly influenced by stimulation of various brain regions. The anterior half of the brain, particularly the frontal lobe, orbital cortex, motor and premotor cortex, anterior portion of the temporal lobe, insula, and cingulate gyrus, contain centers that regulate cardiac function. Stimulation of the midline, ventral, and medial nuclei of the thalamus leads to tachycardia. The heart rate can also be altered by stimulation of the posterior and posterolateral regions of the hypothalamus. Stimuli applied to the H2 field of Forel in the posterior hypothalamus evoke various cardiovascular responses, including tachycardia and associated limb movements, resembling those observed during muscular exercise. The cortical and hypothalamic centers are responsible for initiating cardiac reactions during excitement, anxiety, and other emotional states. They also initiate the cardiac response to changes in environmental temperature. Experimentally induced temperature changes in the preoptic anterior hypothalamus alter the heart rate and peripheral resistance.

Stimulation of the parahypoglossal area of the medulla activates cardiac sympathetic pathways while inhibiting cardiac parasympathetic pathways. Distinct cardiac accelerator sites (increase heart rate) and augmentor sites (increase cardiac contractility) have been identified in certain dorsal regions of the medulla in animals with transected vagus nerves. The right side of the medulla contains a higher number of accelerator regions, while the left side has more prevalent augmentor sites. A similar distribution is observed in the hypothalamus. Thus, the sympathetic fibers primarily descend ipsilaterally through the brainstem.

Cortical centers have a significant impact on autonomic function. The insula plays a distinct role in regulating the balance between sympathetic and parasympathetic actions on the cardiovascular system. Electrical stimulation of the left insular cortex predominantly elicits parasympathetic responses, such as bradycardia and vasodepression, while stimulation of the right insular cortex evokes sympathetic actions, such as tachycardia and vasopression. As predicted, patients with acute stroke-induced damage to the left insular cortex display increased sympathetic tone and a higher risk of arrhythmias and cardiovascular mortality. When the right insular cortex is acutely involved in the stroke, the incidence of cardiovascular mortality/morbidity remains unchanged.

The baroreceptors located in the aortic arch and carotid sinuses are responsible for the baroreceptor reflex. This reflex shows an inverse relationship between heart rate and arterial blood pressure, which is most pronounced over an intermediate range of arterial blood pressures. Below this range, the heart rate maintains a constant, high value, while above this range, the heart rate maintains a constant, low value.

The effects of changes in carotid sinus pressure on the activity in cardiac autonomic nerves are described in Figure 18.4.
Fig. 18.2B ). Nerve terminals take up to 70% of the norepinephrine released during sympathetic stimulation; much of the remainder is carried away by the bloodstream. These processes are slow. Furthermore, the facilitatory effects of sympathetic stimulation on the heart attain steady-state values much more slowly than do the inhibitory effects of vagal stimulation. The onset of the cardiac response to sympathetic stimulation begins slowly for two main reasons. First, norepinephrine appears to be released slowly from the sympathetic nerve terminals. Second, the cardiac effects of the neurally released norepinephrine are mediated mainly by a relatively slow second messenger system involving cyclic adenosine monophosphate (cAMP; see ). Hence, sympathetic activity alters the heart rate and AV conduction much more slowly than vagal activity does. Whereas vagal activity can exert beat-by-beat control of cardiac function, sympathetic activity cannot.
Stimulation of various brain regions can have significant effects on cardiac rate, rhythm, and contractility (see ). In the cerebral cortex, centers that regulate cardiac function are located in the anterior half of the brain, principally in the frontal lobe, the orbital cortex, the motor and premotor cortex, the anterior portion of the temporal lobe, the insula, and the cingulate gyrus. Stimulation of the midline, ventral, and medial nuclei of the thalamus elicits tachycardia. Stimulation of the posterior and posterolateral regions of the hypothalamus can also change the heart rate. Stimuli applied to the H2 field of Forel in the posterior hypothalamus evoke various cardiovascular responses, including tachycardia and associated limb movements; these changes resemble those observed during muscular exercise. Undoubtedly, the cortical and hypothalamic centers initiate the cardiac reactions that occur during excitement, anxiety, and other emotional states. The hypothalamic centers also initiate the cardiac response to alterations in environmental temperature. Experimentally induced temperature changes in the preoptic anterior hypothalamus alter the heart rate and peripheral resistance.
Stimulation of the parahypoglossal area of the medulla reciprocally activates cardiac sympathetic pathways and inhibits cardiac parasympathetic pathways. In certain dorsal regions of the medulla, distinct cardiac accelerator sites (increase the heart rate) and augmentor sites (increase cardiac contractility) have been detected in animals with transected vagus nerves. The accelerator regions are more abundant on the right side, whereas the augmentor sites are more prevalent on the left. A similar distribution also exists in the hypothalamus. Therefore, the sympathetic fibers mainly descend ipsilaterally through the brainstem.
Corticalcentershaveimportanteffectsonautonomicfunction.Theinsulaexertsdistinctregulationofthebalancebetweensympatheticandparasympatheticactionsonthecardiovascularsystem.Inpatientssubjectedtoelectricalstimulation,stimuliappliedtotheleftinsularcortexelicitpredominantlyparasympatheticresponses(bradycardiaandvasodepression),whereasstimuliappliedtotherightinsularcortexevokesympatheticactions(tachycardiaandvasopression).Aspredicted,patientswithacute,stroke-induceddamageoftheleftinsularcortexdisplayincreasedsympathetictoneandanincreasedriskofarrhythmiasandcardiovascularmortality.Whentherightinsularcortexisacutelyinvolvedinthestroke,theincidenceofcardiovascularmortality/morbidityisunchanged.
Fig. 18.4 ). Baroreceptors located in the aortic arch and carotid sinuses are responsible for this reflex (see the section ”). The inverse relationship between heart rate and arterial blood pressure is generally most pronounced over an intermediate range of arterial blood pressures. Below this intermediate range, the heart rate maintains a constant, high value; above this pressure range, the heart rate maintains a constant, low value.
The effects of changes in carotid sinus pressure on the activity in cardiac autonomic nerves are described in
Fig.