Heart innervation

The rhythm of heart contractions depends on many parameters condition of pacemaker cells and the conduction system, myocardial blood flow, and other factors consequently, arrhythmia can originate for different reasons that are caused by disruptions in electrical impulse generation or conduction. They can be caused by heart disease, myocardial ischemia, electrolytic and acid-base changes, heart innervation problems, intoxication of the organism, and so on. 

Drugs used for treating arrhythmia can have an effect on the electrical conduction system of the heart, its excitability, automatism, the size of the effective refractory period, and adrenergic and cholinergic heart innervation. Accordingly, compounds of various chemical classes can restore heart rate disturbances. 

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. 

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). 

When cells lie adjacent to each other in animal tissues, they are often connected by gap junction structures, which permit the passive flow of small molecules from one cell to the other. Such junctions essentially connect the cells metabolically, providing a means of chemical transfer and communication. In certain tissues, such as heart muscle that is not innervated, gap junctions permit very large numbers of cells to act synchronously. Gap junctions also provide a means for transport of nutrients to cells disconnected from the circulatory system, such as the lens cells of the eye. 

Peripheral mAChRs are known to mediate the well-documented actions of ACh at parasympathetically innervated effector tissues (organs) including heart, endocrine and exocrine glands, and smooth muscle tissues [2, 4]. The most prominent peripheral actions mediated by activation of these receptors are reduced heart rate and cardiac contractility, contraction of... 

Ritodrine has an effect on beta (p)2-adrenergic receptors, principally those that innervate the uterus. Stimulation of these p2-adrenergic receptors inhibits uterine smooth muscle contractions. The pradrenergic receptors are located in the heart and are not stimulated by ritodrine when administered as prescribed. Ritodrine is used to... 

Symptoms of intoxication in humans caused by accidental ingestion of Kou-Wen plants have been described as follows. The effect on the digestive system starts with loss of appetite and turn of the stomach, and continues to severe abdominal pain and intestinal bleeding. The effect on the respiratory system presents as breathing difficulties which finally lead to death by respiratory failure. The effect on muscle innervation usually results in generalized muscular weakness and paralysis of the limbs. The effect on the circulatory system starts with heartbeat disorders and a drop in blood pressure, but heart failure is not a common cause of death. In addition to dilation of pupils, a drop in body temperature and proliferation of white blood cells have also been obseryed (70). 

Skeletal muscle is neurogenic and requires stimulation from the somatic nervous system to initiate contraction. Because no electrical communication takes place between these cells, each muscle fiber is innervated by a branch of an alpha motor neuron. Cardiac muscle, however, is myogenic, or self-excitatory this muscle spontaneously depolarizes to threshold and generates action potentials without external stimulation. The region of the heart with the fastest rate of inherent depolarization initiates the heart beat and determines the heart rhythm. In normal hearts, this "pacemaker region is the sinoatrial node. 

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 effects of the autonomic nervous system on MAP are summarized in Figure 15.4. The parasympathetic system innervates the SA node and the AV node of the heart. The major cardiovascular effect of parasympathetic stimulation, by way of the vagus nerves, is to decrease HR, which decreases CO and MAP. 

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. 

HDAC9 is the predominant member of the class II HDAC family expressed in heart (Zhang et al, 2002). Its major product was shown to encode the splice variant MEF2-interacting transcription repressor/histone deacetylase-related protein (MITRIHDRP), which lacks the enzymatic domain but forms complexes with both HDACI and HDAC3 (Zhou et al, 2000 Zhou et al, 2001) and has been recently implicated in skeletal muscle chromatin acetylation and gene expression under motor innervation control (Mejat et al, 2005). 

Acetylcholine is the primary neurotransmitter in the parasympathetic division of the autonomic nervous system, which mainly innervates the gastrointestinal tract, eyes, heart, respiratory tract, and secretory glands. Although its receptors are crucial for maintaining all normal functions of the body, an extremely small number of illnesses can be explained by the dysfunction of cholinergic regions of the peripheral autonomic system. 

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. 

This can be accomplished either by reducing the load on the heart, or by lowering systemic venous and arterial pressure (nitrates and nitrites), or by partial suppression of adrenergic innervation of the heart (j3-adrenoreceptors), or by suppressing calcium ion transport in myocardial cells since the contraction of smooth muscles vessels is controlled by the concentration of calcinm ions in the cytoplasm (Ca channel blockers). The resulting effect of the aforementioned drngs is that they reduce the need for oxygen in the heart. 

Although camosine seems to be primarily associated with the brain and innervated tissues such as muscles (skeletal and heart) at least in the rat (Aldini et al, 2004), camosine has been reported to be present in the eye lens (Quinn et al., 1992), which suggests that its function might not be restricted nervous tissue. 

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... 

Adrenaline is the main hormone released from the adrenal medulla. The glandular cells in this structure correspond to the second, postganglionic neuron of the sympathetic nervous system. Furthermore, adrenaline can be found in chromaffin cells in various tissues. For the better understanding of the function of noradrenaline it is important to realize that this substance, as a neuronal transmitter, affects only the innervated target structure, that is it acts mainly locally. Among these effects are the activation of the musculus dilatator to widen the pupillae in response to a reduced light intensity, an increase in heart rate as a response to a blood pressure drop due to a reduction of the peripheral resistance or constriction... 

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. 

Many visceral organs are innervated by both divisions of the autonomic nervous system. In most instances, when an organ receives dual innervation, the two systems work in opposition to one another. In some tissues and organs, the two innervations exert an opposing influence on the same effector cells (e.g., the sinoatrial node in the heart), while in other tissues opposing actions come about because different effector cells are activated (e.g., the circular and radial muscles in the iris). 

Many neurons of both divisions of the autonomic nervous system are tonicaUy active that is, they are continually carrying some impulse traffic. The moment-to-moment activity of an organ such as the heart, which receives a dual innervation by sympathetic (noradrenergic) and parasympathetic (cholinergic) neurons, is controlled by the level of tonic activity of the two systems. 

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