Heart sympathetic stimulation

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. 

Sympathetic stimulation increases heart rate. Norepinephrine, the neurotransmitter released from sympathetic nerves, binds to the (3-adrenergic receptors in the heart and causes the following effects ... 

The second factor that exerts control on heart rate is the release of the catecholamines, epinephrine and norepinephrine, from the adrenal medulla. Circulating catecholamines have the same effect on heart rate as direct sympathetic stimulation, which is to increase heart rate. In fact, in the intact heart, the effect of the catecholamines serves to supplement this direct effect. In a denervated heart, circulating catecholamines serve to replace the effect of direct sympathetic stimulation. In this way, patients who have had a heart transplant may still increase their heart rate during exercise. 

During exercise when sympathetic stimulation to the heart is increased, the ejection fraction may increase to more than 80% resulting in greater stroke volume and cardiac output. 

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. 

Because baroreceptors respond to stretch or distension of the blood vessel walls, they are also referred to as stretch receptors. A change in blood pressure will elicit the baroreceptor reflex, which involves negative feedback responses that return blood pressure to normal (see Figure 15.6). For example, an increase in blood pressure causes distension of the aorta and carotid arteries, thus stimulating the baroreceptors. As a result, the number of afferent nerve impulses transmitted to the vasomotor center increases. The vasomotor center processes this information and adjusts the activity of the autonomic nervous system accordingly. Sympathetic stimulation of vascular smooth muscle and the heart is decreased and parasympathetic stimulation of the heart is increased. As a result, venous return, CO, and TPR decrease so that MAP is decreased back toward its normal value. 

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. 

In other words, the increase in cardiac output occurs by extrinsic (sympathetic stimulation) and intrinsic (increased VR and the Frank-Starling law of the heart) mechanisms. Venous return is also markedly increased by the compression of blood vessels in the working muscles. TTie increase in CO causes an increase in MAP, and the increase in MAP contributes to an increase in muscle blood flow. 

Loss of plasma volume leads to a decrease in MAP. Baroreceptors located in the aortic and carotid sinuses detect this fall in MAP and elicit reflex responses that include an increase in the overall activity of the sympathetic nervous system. Sympathetic stimulation of the heart and blood vessels leads to an increase in cardiac output (CO) and increased total peripheral resistance (TPR). These adjustments, which increase MAP, are responsible for the short-term regulation of blood pressure. Although increases in CO and TPR are effective in temporary maintenance of MAP and blood flow to the vital organs, these activities cannot persist indefinitely. Ultimately, plasma volume must be returned to normal (see Table 19.1). 

Angiotensin-II AT, Human cDNA Artherosderosis, cardiac hypertrophy, congestive heart failure, hypertension, myocardial infarction, renal disease, cancer, diabetes, obesity, glaucoma, cystic fibrosis, Alzheimer s disease, Parkinson s disease Smooth muscle contraction, cell proliferation and migration, aldosterone and ADH release, central and peripheral sympathetic stimulation, extracellular matrix formation, tubular sodium retention, neuroprotection... 

The most important actions of the (3-blocking drugs are on the cardiovascular system. -Blockers decrease heart rate, myocardial contractility, cardiac output, and conduction velocity within the heart. These effects are most pronounced when sympathetic activity is high or when the heart is stimulated by circulating agonists. 

SA node and A-V fibers become dominant. Activation of M2 receptors increases the potassium permeability and reduces cAMP levels, slowing the rate of depolarization and decreasing the excitability of SA node and A-V fiber cells. This results in marked bradycardia and a slowing of A-V conduction that can override the stimulation of the heart by catecholamines released during sympathetic stimulation. In fact, very high doses of a muscarinic agonist can produce lethal bradycardia and A-V block. Choline esters have relatively minor direct effects on ventricular function, but they can produce negative inotropy of the atria. 

In therapeutic doses, hydralazine produces little effect on nonvascular smooth muscle or on the heart. Its pharmacological actions are largely confined to vascular smooth muscle and occur predominantly on the arterial side of the circulation venous capacitance is much less affected. Because cardiovascular reflexes and venous capacitance are not affected by hydralazine, postural hypotension is not a clinical concern. Hydralazine treatment does, however, result in an increase in cardiac output. This action is brought about by the combined effects of a reflex increase in sympathetic stimulation of the heart, an increase in plasma renin, and salt and water retention. These effects limit the hypotensive usefulness of hydralazine to such an extent that it is rarely used alone. 

In patients with coronary insufficiency, a -blocker can be given in conjunction with diazoxide to decrease the cardiac work associated with reflex increases in sympathetic stimulation of the heart. However, 3-blockers potentiate the hypotensive effect of diazoxide, and therefore, the dose of the vasodilator should be lowered. The dose of diazoxide should also be lowered if the patient has recently been treated with guanethidine or another drug that depresses the action of the sympathetic nervous system. Such drugs permit a greater hypotensive effect because they reduce the increase in cardiac output that normally partially counteracts the fall in pressure. 

Isoflurane (Forane) is a structural isomer of enflurane and produces similar pharmacological properties some analgesia, some neuromuscular blockade, and depressed respiration. In contrast, however, isoflurane is considered a particularly safe anesthetic in patients with ischemic heart disease, since cardiac output is maintained, the coronary arteries are dilated, and the myocardium does not appear to be sensitized to the effects of catecholamines. Also, blood pressure falls as a result of vasodilation, which preserves tissue blood flow. Isoflurane causes transient and mUd tachycardia by direct sympathetic stimulation this is particularly important in the management of patients with myocardial ischemia. 

The drug increases the heart rate, cardiac output and blood pressure which is due to sympathetic stimulation. Respiration is not depressed, muscle tone increases and reflexes are not abolished during anaesthesia. Ketamine has been recommended for short operations, unpleasant therapeutic and diagnostic procedures in children, operation in shocked patients and in obstetrics. 

Transient elevations in blood pressure and heart rate occur with seizures, probably as a result of increased sympathetic stimulation that leads to increases in norepinephrine levels. Hypertension or increased pretreatment heart rate are strongly predictive of peak postictal change in both heart rate and blood pressure ( 38). Increased parasympathetic stimulation decreases the heart rate as a result of inhibition of the sinoatrial node. Stimulation of the adrenal cortex leads to increased plasma corticosteroids and stimulation of the adrenal medulla, which may also contribute to increases in blood pressure and heart rate. 

Atomoxetine is a selective inhibitor of the norepinephrine reuptake transporter. Its actions, therefore, are mediated by potentiation of norepinephrine levels in noradrenergic synapses. It is used in the treatment of attention deficit disorders (see below). Atomoxetine has surprisingly little cardiovascular effect because it has a clonidine-like effect in the central nervous system to decrease sympathetic outflow while at the same time potentiating the effects of norepinephrine in the periphery. However, it may increase blood pressure in some patients. Norepinephrine reuptake is particularly important in the heart, particularly during sympathetic stimulation, and this... 

The most important stimulus to the release of ANP from the heart is atrial stretch via mechanosensitive ion channels. ANP release is also increased by volume expansion, changing from the standing to the supine position, and exercise. ANP release can also be increased by sympathetic stimulation via aiA-adrenoceptors, endothelins via the -receptor subtype (see below), glucocorticoids, and vasopressin. Plasma ANP concentration increases in various pathologic states, including heart failure, primary aldosteronism, chronic renal failure, and inappropriate ADH secretion syndrome. 

In addition to its effects on cardiac contractility, digitalis has a direct inhibitory effect on sympathetic nervous system activity.37,60 This effect is beneficial because it decreases stress on the failing heart by decreasing excessive sympathetic stimulation of the heart and peripheral vasculature2. Therapeutic levels of digitalis likewise stabilize heart rate and slow impulse conduc-... 

Beta blockers bind to beta-1 receptors on the myocardium and block the effects of norepinephrine and epinephrine (see Chapter 20). These drugs therefore normalize sympathetic stimulation of the heart and help reduce heart rate (negative chronotropic effect) and myocardial contraction force (negative inotropic effect). Beta blockers may also prevent angina by stabilizing cardiac workload, and they may prevent certain arrhythmias by stabilizing heart rate.40 These additional properties can be useful to patients with heart failure who also have other cardiac symptoms. 

Sympathetic stimulation — increasing the heart rate to maintain contractility and cardiac output. 

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