Heart rate, control sympathetic

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

In randomized, controlled, clinical trials, calcium channel blockers were as effective as p-blockers at preventing ischemic symptoms. Calcium channel blockers are recommended as initial treatment in IHD when /3-blockers are contraindicated or not tolerated. In addition, CCBs may be used in combination with /3-blockers when initial treatment is unsuccessful. However, the combination of a (1-blocker with either verapamil or diltiazem should be used with extreme caution since all of these drugs decrease AV nodal conduction, increasing the risk for severe bradycardia or AV block when used together. If combination therapy is warranted, a long-acting dihydropyridine CCB is preferred. (3-Blockers will prevent reflex increases in sympathetic tone and heart rate with the use of calcium channel blockers with potent vasodilatory effects. 

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 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. 

The resting heart rate of 60-80 bpm results from dominant vagal tone. The intrinsic rate generated by the sinoatrial (SA) node is 110 bpm. Control of heart rate is, therefore, through the balance of parasympathetic and sympathetic activity via the vagus and cardioaccelerator (T1-T5) fibres, respectively. 

The autonomic nervous system is divided into the sympathetic and parasympathetic components, which typically exert opposing effects. The sympathetic system is involved in the fight or flight reaction (increased blood pressure and heart rate, and accommodation for increased vision, for example) that prepares the organism for stressful situations. The parasympathetic system conversely establishes a more relaxed situation, for instance, the rest period after a meal. The autonomic nervous system that is responsible for the independent control of the mechanical and secretory functions of the gastrointestinal tract is sometimes called the enteric system. 

Autonomic and hormonal control of cardiovascular function. Note that two feedback loops are present the autonomic nervous system loop and the hormonal loop. The sympathetic nervous system directly influences four major variables peripheral vascular resistance, heart rate, force, and venous tone. It also directly modulates renin production (not shown). The parasympathetic nervous system directly influences heart rate. In addition to its role in stimulating aldosterone secretion, angiotensin II directly increases peripheral vascular resistance and facilitates sympathetic effects (not shown). The net feedback effect of each loop is to compensate for changes in arterial blood pressure. Thus, decreased blood pressure due to blood loss would evoke increased sympathetic outflow and renin release. Conversely, elevated pressure due to the administration of a vasoconstrictor drug would cause reduced sympathetic outflow, reduced renin release, and increased parasympathetic (vagal) outflow. 

The projection from the locus coeruleus to limbic cortex may regulate emotions, as well as energy, fatigue, and psychomotor agitation or psychomotor retardation (Fig. 5—26). A projection to the cerebellum may regulate motor movements, especially tremor (Fig. 5—27). Brainstem norepinephrine in cardiovascular centers controls blood pressure (Fig. 5—28). Norepinephrine from sympathetic neurons leaving the spinal cord to innervate peripheral tissues control heart rate (Fig. 5—29) and bladder emptying (Fig. 5—30). 

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. 

MR are present in, e.g. the central nervous system (CNS, for respiratory and cardiovascular activity, cognition and stress processing), peripheral nervous system (PNS, for smooth muscle contraction, control of heart rate, vasodilatation), as well as the sympathetic and parasympathetic ganglion cells [1], Five metabotropic cholinergic MR subtypes (M1-M5) were identified [1], but selectivity of TA is merely apparent [9] except for tiotropium and ipratropium [31]. 

Norepinephrine Mostly excitatory, but inhibitory in some areas. Secreted by neurons in the locus ceruleus (subcortical area) to widespread areas of the brain, controlling wakefulness, overall activity, and mood. Also diffusely secreted in the sympathetic nervous system. Diffuse and widespread symptoms, including depression, changes in blood pressure, heart rate, and diffuse physiological responses, among many others. An important transmitter in the sympathetic branch of the autonomic nervous system. Diffusely affected by many medications. Several antidepressants work specifically on this neurotransmitter and its receptor sites. Many medications for general medical conditions affect this neurotransmitter as well. 

The effects of intramuscular premedication with either clonidine 2 micrograms/kg or midazolam 70 micrograms/ kg on perioperative responses to ketamine anesthesia have been assessed in a placebo-controlled study in 30 patients (14). Clonidine significantly reduced intraoperative oxygen consumption, mean arterial pressure, and heart rate compared with midazolam and placebo. Thus, clonidine was as effective as midazolam, the standard drug used for this purpose, in reducing the undesirable sympathetic stimulation of ketamine. 

In the peripheral nervous system, norepinephrine is an important neurotransmitter in the sympathetic branch of the autonomic system. Sympathetic nerve transmission operates below the level of consciousness in controlling physiological function of many organs and tissues of the body. The sympathetic system plays a particularly important role in regulating cardiovascular function in response to postural, exertional, thermal, and mental stress. With sympathetic activation, the heart rate is increased, peripheral arterioles are constricted, skeletal arterioles are dilated, and the blood pressure is elevated. In addition, sympathetic nerve stimulation dilates pupils inhibits smooth muscles of the intestines, bronchi, and bladder and closes the sphincters. Sympathetic signals work in balance with the parasympathetic portion of the autonomic nervous system to maintain a stable internal environment. 

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