Control of heart rate

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. 

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  

Parasympathetic stimulation decreases heart rate. Acetylcholine, the neurotransmitter released from the vagus nerve (the parasympathetic nerve to the heart), binds to muscarinic receptors and causes the following effects  

At rest, the parasympathetic system exerts the predominant effect on the SA node and therefore on heart rate. In a denervated heart, such as a trans- 

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. 

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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. 

Dihydropyridine channel blockers (e.g., nifedipine) have little benefit on clinical outcomes beyond symptom relief. The role of verapamil and diltiazem appears to be limited to symptom relief or control of heart rate in patients with supraventricular arrhythmias in whom /l-blockers are contraindicated or ineffective. 

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. 

Muscarinic M2 receptor CHRM2 Agonism Vagal effects (key role in the control of heart rate and smooth muscle activity) Bradycardia. Antagonism May induce cardiac side effects (palpitations, dysrhythmia) or peripheral edema, bronchoconstriction can result from presynaptic M2 receptor antagonism if postsynaptic M3 receptors are not also blocked. 

Some are inhibited by ATP 173 l7 lb and others by eicosanoids475 or inositol hexaphosphate.476 Some of the ATP-sensitive channels contain an ABC transporter subunit and are binding sites for sulfonylureas and other drugs. See discussion on p. 421. A number of human disorders in Kir channels have been identified.468 Tire human Kir channels participate in regulation of resting membrane potentials in K+ homeostasis, control of heart rate, and hormone secretion.468 A third group of K+ channels are dimeric, but each subunit contains two tandem P regions and 4-8 transmembrane helices.455... 

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]. 

Gray RJ, Bateman TM, Czer LS, Conklin CM, Matloff JM. Esmolol a new ultrashort-acting beta-adrenergic blocking agent for rapid control of heart rate in postoperative supraventricular tachyarrhythmias. J Am Coll Cardiol 1985 5(6) 1451-6. 

DiFrancesco D, Borer JS. The funny current Cellular basis for the control of heart rate. Drugs. 2007 67(15) 15-24. 

Although earlier trials suggested that verapamil and diltiazem may provide improved benefit in selected patients, the large Incomplete Infarction Trial of European Research Collaborators Evaluating Prognosis post-Thrombolysis (INTERCEPT) has dampened the interest for the use of diltiazem in patients receiving fibrinolytics. In this trial, the use of extended-release diltiazem had no effect on the 6-month risk of cardiac death, MI, or recurrent ischemia. Therefore, the role of verapamil or diltiazem appears to be limited to relief of ischemia-related symptoms or control of heart rate in patients with supraventricular arrhythmias for whom /8-blockers are contraindicated or ineffective. ... 

The ANS is the major involuntary portion of the nervous system and is responsible for automatic, unconscious bodily functions, such as control of heart rate and blood pressure and both gastrointestinal and genitourinary functions. The ANS is divided into two major subcategories the parasympathetic autonomic nervous system (PANS) and the sympathetic autonomic nervous system (SANS). 

Figure 11-4-3. Algorithm Reflex Control of Heart Rate...

Randomized, Prospective Comparison of Halothane, Isoflurane, and Enflurane on Baroreflex Control of Heart Rate in Humans Michael Muzi and Thomas J. Ebert... 

Skill Keeper Autonomic Control of Heart Rate (see Chapter 6)... 

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