Sympathetic nervous system, cardiac

Automaticity of cardiac fibers is controlled in part by activity of the sympathetic and parasympathetic nervous systems. Enhanced activity of the sympathetic nervous system may result in increased automaticity of the SA node or other automatic cardiac fibers. Enhanced activity of the parasympathetic nervous system tends to suppress automaticity conversely, inhibition of activity of the parasympathetic nervous system increases automaticity. Other factors may lead to abnormal increases in automaticity of extra-SA nodal tissues, including hypoxia, atrial or ventricular stretch [as might occur following long-standing hypertension or after the development of heart failure (HF)], and electrolyte abnormalities such as hypokalemia or hypomagnesemia. 

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.

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). 

As cardiac function decreases after myocardial injury, the heart relies on the following compensatory mechanisms (1) tachycardia and increased contractility through sympathetic nervous system activation (2) the Frank-Starling mechanism, whereby increased preload increases stroke volume (3) vasoconstriction and (4) ventricular hypertrophy and remodeling. Although these compensatory mechanisms initially maintain cardiac function, they are responsible for the symptoms of HF and contribute to disease progression. 

Nesiritide is manufactured using recombinant techniques and is identical to the endogenous B-type natriuretic peptide secreted by the ventricular myocardium in response to volume overload. Consequently, nesiritide mimics the vasodilatory and natriuretic actions of the endogenous peptide, resulting in venous and arterial vasodilation increases in cardiac output natriuresis and diuresis and decreased cardiac filling pressures, sympathetic nervous system activity, and renin-angiotensin-aldosterone system activity. 

In addition to its pump function, the heart is also a secretory organ. Cardiac cells produce two small peptides, the natriuretic factors, which oppose the vasoconstrictive actions of noradrenaline (norepinephrine) from the sympathetic nervous system and of the peptide angiotensin II. By causing vasodilation and natriuresis (increased excretion of sodium in the urine), atrial natriuretic peptide (ANP) secreted from the atria and B-type natriuretic peptide (BNP) secreted by both atria and probably more significantly, from the ventricles, reduce blood pressure. The stimulus to secretion of natriuretic peptides is wall stretch of the chambers of the heart, indicating volume and pressure overload of the vascular system. A third member of the natriuretic peptide family, CNP, is secreted by endothelial cells. 

The sympathetic nervous system plays an important role in the involuntary regulation of cardiac activity, vascular tonicity, functional activity of smooth muscle, and glands by releasing endogenic adrenergic substances, cateeholines, from peripheral nerve endings into the synapses of the central nervous system (CNS). 

Noradrenaline and adrenaline are the classic catecholamines and neurotransmitters in the sympathetic nervous system. Noradrenaline stimulates the following subtypes of adrenoceptors P, a, U2. It has positive inotropic and chronotropic activities as a result of /3i-receptor stimulation. In addition, it is a potent vasoconstrictor agent as a result of the stimulation of both subtypes (ai,a2) of a-adrenoceptors. After intravenous infusion, its effects develop within a few minutes, and these actions disappear within 1-2 minutes after stopping the infusion. It may be used in conditions of acute hypotension and shock, especially in patients with very low vascular resistance. It is also frequently used as a vasoconstrictor, added to local anaesthetics. Adrenaline stimulates the following subtypes of adrenoceptors /3i, P2, oil, 0L2. Its pharmacological profile greatly resembles that of noradrenaline (see above), as well as its potential applications in shock and hypotension. Like noradrenaline, its onset and duration of action are very short, as a result of rapid inactivation in vivo. Both noradrenaline and adrenaline may be used for cardiac stimulation. Their vasoconstrictor activity should be kept in mind. A problem associated with the use of /3-adrenoceptor stimulants is the tachyphylaxis of their effects, explained by the /3-adrenoceptor downregulation, which is characteristic for heart failure. 

E. The effect of ganglionic blockade depends upon the predominant autonomic tone exerted within various organ systems. Since the activity of the parasympathetic nervous system predominates in the eye, the effect of ganglionic blockade is mydriasis, not miosis. Similarly, stimulation of the genital tract and urinary retention would be decreased. Since sympathetic nervous system activity predominates in blood vessels and the ventricles, vasodilation and a decreased cardiac output would follow ganglionic blockade. 

The net effects of bretylium on the electrical and mechanical properties of the heart are a composite of the direct actions of the drug on cardiac tissues and indirect actions mediated through the drug s effects on the sympathetic nervous system. 

Thus, it seems that the lack of sympathetic nervous system inhibition produced by the vasodilators, which is advantageous in some ways, can also be a disadvantage in that reflex increases in sympathetic nerve activity will lead to hemodynamic changes that reduce the effectiveness of the drugs. Therefore, the vasodilators are generally inadequate as the sole therapy for hypertension. However, many of the factors that limit the usefulness of the vasodilators can be obviated when they are administered in combination with a -adrenoceptor antagonist, such as propranolol, and a diuretic. Propranolol reduces the cardiac stimulation that occurs in response to increases in sympathetic nervous activity, and the... 

Hydralazine is generally reserved for moderately hypertensive ambulatory patients whose blood pressure is not well controlled either by diuretics or by drugs that interfere with the sympathetic nervous system. It is almost always administered in combination with a diuretic (to prevent Na+ retention) and a p-blocker, such as propranolol (to attenuate the effects of reflex cardiac stimulation and hyperreninemia). The triple combination of a diuretic, -blocker, and hydralazine constitutes a unique hemodynamic approach to the treatment of hypertension, since three of the chief determinants of blood pressure are affected cardiac output (p-blocker). 

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. 

Neurohumoral (extrinsic) compensation involves two major mechanisms (previously presented in Figure 6-7)—the sympathetic nervous system and the renin-angiotensin-aldosterone hormonal response—plus several others. Some of the pathologic as well as beneficial features of these compensatory responses are illustrated in Figure 13-2. The baroreceptor reflex appears to be reset, with a lower sensitivity to arterial pressure, in patients with heart failure. As a result, baroreceptor sensory input to the vasomotor center is reduced even at normal pressures sympathetic outflow is increased, and parasympathetic outflow is decreased. Increased sympathetic outflow causes tachycardia, increased cardiac contractility, and increased vascular tone. Vascular tone is further increased by angiotensin II and endothelin, a potent vasoconstrictor released by vascular endothelial cells. The result is a vicious cycle that is characteristic of heart failure (Figure 13-3). Vasoconstriction increases afterload, which further reduces ejection fraction and cardiac output. Neurohumoral antagonists and vasodilators... 

Recall that scopolamine, an ingredient in henbane, blocks muscarinic acetylcholine receptors. This blockade essentially removes the influence of the parasympathetic nervous system on the body. In the absence of this influence, the balance of forces is upset and the sympathetic nervous system gains the upper hand thus, your heart rate increases, your pupils dilate, salivation stops, your ability to urinate is impaired, and you become constipated overall, things get very uncomfortable. But none of this is directly lethal (unless the constipation makes one commit suicide). If you do die from an overdose of henbane, it is believed to result from either a complex series of events in your brain that lead to the loss of control of your diaphragm, causing death from asphyxiation, or from cardiac arrest. This is why the deadly nightshade is so deadly and how Shakespeare chose to kill King Hamlet with henbane. 

Drugs that block beta-1 receptors on the myocardium are one of the mainstays in arrhythmia treatment. Beta blockers are effective because they decrease the excitatory effects of the sympathetic nervous system and related catecholamines (norepinephrine and epinephrine) on the heart.5,28 This effect typically decreases cardiac automaticity and prolongs the effective refractory period, thus slowing heart rate.5 Beta blockers also slow down conduction through the myocardium, and are especially useful in controlling function of the atrioventricular node.21 Hence, these drugs are most effective in treating atrial tachycardias such as atrial fibrillation.23 Some ventricular arrhythmias may also respond to treatment with beta blockers. 

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