Heart sympathetic innervation

Isoproterenol. Isoproterenol hydrochloride is an nonselective P-adrenoceptor agonist that is chemically related to NE. It mimics the effects of stimulation of the sympathetic innervation to the heart which are mediated by NE. It increases heart rate by increasing automaticity of the SA and AV nodes by increasing the rate of phase 4 diastoHc depolarization. It is used in the treatment of acute heart block and supraventricular bradyarrhythmias, although use of atropine is safer for bradyarrhythmias foUowing MI (86). 

Bengel FM, Permanetter B, Ungerer M, Nekolla SG, Schwaiger M. Relationship between altered sympathetic innervation, oxidative metabolism and contractile function in the cardiomyopathic human heart a non-invasive study using positron emission tomography. Eur Heart J 2001 22 1594-1600... 

Bengel PM, Ueberfuhr P, Ziegler SI, Nekolla SG, Odaka K, Reichart B et al. Non-invasive assessment of the effect of cardiac sympathetic innervation on metabolism of the human heart. Eur J Nucl Med 2000 27 1650-1657... 

Adrenoceptors of the /3-subtype are important mediators of the sympathetic activation of the heart, kidney, and bronchi. /3-Adrenoceptors are also found in other organs and tissues such as blood vessels and the central nervous system. Accordingly, /3-adrenoceptor antagonists or jS-blockers inhibit the stimulating influence of the endogenous catecholamines (noradrenaline, adrenaline) on the various organs and tissues which are subject to sympathetic innervation. In cardiovascular medicine the /3-blockers are used in particular to blunt the sympathetic activation of the heart and kidneys. These effects are mediated by the /3i-subtype of the /3-adrenoceptors. The currently used /3-blockers are all competitive antagonists of the /3i-adrenoceptor, which is the basis of their therapeutic application. 

The heart is innervated by both sympathetic and parasympathetic neurons however, their distribution in the heart is quite different. Postganglionic noradrenergic fibers from the stellate and inferior cervical ganglia innervate the sinoatrial (S-A) node and myocardial tissues of the atria and ventricles. Activation of the sympathetic outflow to the heart results in an increase in rate (positive chronotropic effect), in force of contraction (positive inotropic effect), conduction tissue (positive dro-motropic effect). 

In summary, several F-labeled radioligands for the imaging of the sympathetic innervation of the heart are available. Several 6-[ 8F]FDA PET studies in humans have already been performed. It is indeed worthwhile to also continue with the evaluation of the preclinical cardiac innervation tracers, such as 4-[ 8F]FMR and P8F1FIBG, because of their partly superior in vivo potential. 

Except for skeletal muscle, virtually all tissues in the body are innervated in some way by the ANS.9 Table 18-1 summarizes the innervation and effects of the sympathetic and parasympathetic divisions on some of the major organs and tissues in the body. As indicated in Table 18-1, some organs, such as the heart, are innervated by both sympathetic and parasympathetic neurons. Other tissues, however, may only be supplied by the sympathetic division. The peripheral arterioles, for instance, are innervated by the sympathetic division but receive no parasympathetic innervation. 

Bradycardia occurs in some 3% of spinal anesthetics in adults. Bradycardia can lead to cardiac arrest, either by direct block of the sympathetic innervation of the heart (in unintended high block) or as a consequence of insufficient venous return. In 900 cases of major anesthetic mishaps giving rise to compensation claims, there were 14 cases of cardiac arrest under spinal anesthesia, of which six were fatal (191). Myocardial infarction and cardiac arrest preceded by atrioventricular block have also been described. 

The heart responds constantly to hormonal and nervous system signals. Sympathetic nervous system terminals releasing norepinephrine are found in cardiac cells of the atria and ventricles. This allows for reflex regulation of heart muscle contractility. Sympathetic innervation is also present to the SA node and AV junction, where norepinephrine release acts to increase heart rate (enhanced phase 4 depolarization) and also to increase conduction velocity by reducing the AV junction impedance to conduction. Parasympathetic innervation is provided by cranial nerve 10, the vagus nerve, to the SA node and the AV junction. These fibers release acetylcholine, which slows SA node activity (decreasing the rate of phase 4 depolarization) and decreases conduction throughout the AV junction. 

In addition to studies of (3-ARs, PET has been used to investigate the integrity of presynaptic sympathetic innervation of the heart. Three tracers have mainly been used for this purpose [ F]fluorometaraminol (Wieland et al., 1990), [ F]fluorodopamine (Goldstein et al., 1990) and ["C]/n-hydroxyephedrine (["C]HED) (Schwaiger et al.,... 

These tracers compete with endogenous noradrenalin for transport into pre-synaptic nerve terminals via the neuronal uptake-1 transport system. Once within the neuron, these tracers are not susceptible to metabolism and serve as markers of sympathetic innervation. Recent studies show decreased retention of ["C]HED in patients after cardiac transplant, consistent with heart denervation (Schwaiger et al., 1991). With time, some sympathetic reinnervation occurred particularly in the antero-septal regions of the heart. This correlates with recovery of the sensation of angina pectoris in these patients (Stark et al.,... 

The heart is innervated by both sympathetic and parasympathetic nerve fibers of the autonomic nervous system. Although the heart can generate its own heartbeat independently of nervous control, stress, exercise, and physical trauma make it advantageous to adjust cardiac contraction to meet the needs at the time. Thus, the cardiovascular control system (Figure 6.20.5), which is located in the brain, controls the contractility of the myocardium (the muscle of the heart), and produces both inotrophic (force of contraction) and chronotrophic (rate of contraction) effects. 

Striated muscle fibres (as in the diaphragm) and uterine muscle lack sympathetic innervation and have receptors of the j82 type. They respond strongly to the hormone (epinephrine) and not to the neurotransmitter (norepinephrine). Sympathetically innervated tissue, on the other hand (e.g. heart and duodenum), has an excess of jSi-over jS2-receptors. 

Stimulation of the sympathetic innervation to the heart results in tachycardia, augmented myocardial contractility, and increased aortic blood pressure, accompanied by an increase in coronary blood flow. The increase in coronary blood flow is secondary to the augmented myocardial oxygen consumption mediated by a local metabolic mechanism. However the direct effect of activation of sympathetic fibers to the cornary vessels is predominantly coronary vasoconstriction mediated by adrenergic alpha receptors. 

The increased force of contraction induced by NA in the heart muscle is one of the consequences which follow when the sympathetic innervation to the heart is stimulated. This response is mediated by sympathetic receptors which are classified as of the j9 type, since the effects are more potently produced by iso-prenaline. and are antagonized by -antagonist drugs but not by a-antag(mist drugs. Biochemical studies of the effects of catecholamines on the isolated perfused heart have shown that the inotropic effect is accompanied by a large rise in the intracellular concentration of cyclic AMP in the cardiac cells. Furthermore, this rise occurs very rapidly after exposure to the catecholamine, and slightly precedes the recorded inotropic effect (Fig. 14). There is an excellent correlation between the... 

The autonomic nervous system guides the electrical and mechanical functions of the heart. The heart is innervated by both the sympathehc and parasympathetic systems, which have opposite effects and are activated reciprocally. They play important roles in arrhythmia susceptibility. Sympathetic shmulation originates from the intermediolateral column of the thoracic spinal cord. Its neurotransmitter, norepinephrine, is released from neurons of postganglionic fibers of stellate ganglia and epinephrine is released from the adrenal medulla. Both of these act on cardiac p-adrenergic receptors. Sympathetic nerves are predominantly on... 

Dmgs that mimic or inhibit the actions of neurotransmitters released from parasympathetic or sympathetic nerves innervating the heart may also be used to treat supraventricular bradyarrhythmias, heart block, and supraventricular tachyarrhythmias. Those used in the treatment of arrhythmias may be found in Table 1. 

Because cardiac muscle is myogenic, nervous stimulation is not necessary to elicit the heart beat. However, the heart rate is modulated by input from the autonomic nervous system. The sympathetic and parasympathetic systems innervate the SA node. Sympathetic stimulation causes an increase in heart rate or an increased number of beats/min. Norepinephrine, which stimulates ( -adrenergic receptors, increases the rate of pacemaker depolarization by increasing the permeability to Na+ and Ca++ ions. If the heart beat is generated more rapidly, then the result is more beats per minute. 

The autonomic nervous system exerts the primary control on heart rate. Because the sympathetic and parasympathetic systems have antagonistic effects on the heart, heart rate at any given moment results from the balance or sum of their inputs. The SA node, which is the pacemaker of the heart that determines the rate of spontaneous depolarization, and the AV node are innervated by the sympathetic and parasympathetic systems. The specialized ventricular conduction pathway and ventricular muscle are innervated by the sympathetic system only. 

The sympathetic system innervates most tissues in the heart including the SA node, AV node, and ventricular muscle. Sympathetic stimulation causes an increase in HR as well as an increase in ventricular contractility, which... 

The sympathetic system also innervates vascular smooth muscle and regulates the radius of the blood vessels. All types of blood vessels except capillaries are innervated however, the most densely innervated vessels include arterioles and veins. An increase in sympathetic stimulation of vascular smooth muscle causes vasoconstriction and a decrease in stimulation causes vasodilation. Constriction of arterioles causes an increase in TPR and therefore MAP. Constriction of veins causes an increase in venous return (VR) which increases end-diastolic volume (EDV), SV (Frank-Starling law of the heart), CO, and MAP. 

Figure 15.5 Effects of sympathetic and parasympathetic nervous activity on mean arterial pressure. The parasympathetic nervous system innervates the heart and therefore influences heart rate and cardiac output. The sympathetic nervous system innervates the heart and veins and thus influences cardiac output. This system also innervates the arterioles and therefore influences total peripheral resistance. The resulting changes in cardiac output and total peripheral resistance regulate mean arterial pressure.

Sympathetic stimulation of veins. The smaller, more compliant veins that serve generally as blood reservoirs as well as specific blood reservoirs are densely innervated by the sympathetic system. Stimulation of the vascular smooth muscle in the walls of these vessels causes vasoconstriction and a decrease in venous compliance. Vasoconstriction increases venous pressure in the veins the blood is squeezed out of the veins and, due to the presence of one-way valves, moves toward the heart so that VR increases. A decrease in sympathetic stimulation allows the veins to relax and distend. The vessels become more compliant and capable of holding large volumes of blood at low pressures. In this case, VR decreases. 

This group consists of j3-adrenergic receptor blockers, the antiarrhythmic activity of which is associated with inhibition of adrenergic innervation action of the circulatory adrenaline on the heart. Because all 8-adrenoblockers reduce stimulatory sympathetic nerve impulses of catecholamines on the heart, reduce transmembrane sodium ion transport, and reduce the speed of conduction of excitation, sinoatrial node and contractibility of the myocardium is reduced, and automatism of sinus nodes is suppressed and atrial and ventricular tachyarrhythmia is inhibited. 

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