Chronotropic activity

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. 

In vivo, racemic dobutamine increases the inotropic activity of the heart to a much greater extent than it increa.ses chronotropic activity. This pharmacological profile has led to its use in treating congestive heart failure. Since /3 receptors are involved positively in both inotropic and chronotropic effects of the heart, the selective inotropic effect. seen with dobutamine cannot simply be due to its activity at P% receptors. Rather, this effect is the result of a combination of the inotropic effect of (-t- )-dohutamine on Px receptors and that of (-)-dobutamine mediated through 0 receptors. Thus, this is a case where a racemic mixture provides a more desirable pharmacological and therapeutic cITect than would cither enantiomer alone. 

Milrinone is a member of a new class of bipyridine inotropic/vasodilator agents with phosphodiesterase inhibitor activity. It is a positive inotrope and vasodilator, with little chronotropic activity, different in structure and mode of action from either the digitalis glycosides or catecholamines (see also Figures 23 and 42). 

Not necessarily. The most efficacious combinations are those in which the mechanisms of action of the drugs compliment each other. For example, diltiazem, with strong cardiodepressant actions, would not be suitable in combination with propranolol, which also has negative inotropic and chronotropic activity. 

Extracts of A. carmichaelUhave shown cardiotonic activity, including inotropic and chronotropic activities, leading to hypotension and/or hypertension. Analgesic and anesthetic activities have been reported. Hyoscine potentiates the action of aconitine. Aconitine and related compounds exhibit anti-inflammatory and analgesic properties in experimental animals. lateral rootlets of A. carmichaelii (considered a separate drug in Chinese tradition), has been shown to raise the heart rate in sinus arrhjdhmia patients. ... 

The histamine H2-receptor (359 amino acids) is best known for its effect on gastric acid secretion. Histamine H2-receptor activation, in conjunction with gastrin and acetylcholine from the vagus, potently stimulate acid secretion from parietal cells. High concentrations of histamine are also present in cardiac tissues and can stimulate positive chronotropic and inotropic effects via H2-receptor stimulation and activation of adenylyl... 

Another mechanism to maintain CO when contractility is low is to increase heart rate. This is achieved through sympathetic nervous system (SNS) activation and the agonist effect of norepinephrine on P-adrenergic receptors in the heart. Sympathetic activation also enhances contractility by increasing cytosolic calcium concentrations. SV is relatively fixed in HF, thus HR becomes the major determinant of CO. Although this mechanism increases CO acutely, the chronotropic and inotropic responses to sympathetic activation increase myocardial oxygen demand, worsen underlying ischemia, contribute to proarrhythmia, and further impair both systolic and diastolic function. 

Isoproterenol (104) is an important agent for classification because of its selective p-receptor agonist activity. It is of special interest that its chronotropic (increase in heart rate) and inotropic (increase in force of contraction) effects exceed that of epinephrine it is also used in the management of mild to moderate asthma due to its bronchodilating effect, resulting in increased vital capacity of the lungs. 

The answer is d. (Katzung, p 130J Epinephrine has a positive ionotropic and chronotropic effect on the heart because of its pradrenergic activity It also has a-adrenergic activity that causes vasoconstriction in the vascular beds. These actions result in a rise in systolic blood pressure. Epinephrine also has p2-adrenergic activity, which causes vasodilation in skeletal muscle. Because of this latter effect, total peripheral resistance can fall, resulting in a drop in diastolic pressure, particularly at low doses of epinephrine. 

Cardiostimulation. By stimulating Pi-receptors, hence activation of ade-nylatcyclase (Ad-cyclase) and cAMP production, catecholamines augment all heart functions, including systolic force (positive inotropism), velocity of shortening (p. clinotropism), sinoatrial rate (p. chronotropism), conduction velocity (p. dromotropism), and excitability (p. bathmotropism). In pacemaker fibers, diastolic depolarization is hastened, so that the firing threshold for the action potential is reached sooner (positive chronotropic effect, B). The cardiostim-ulant effect of p-sympathomimetics such as epinephrine is exploited in the treatment of cardiac arrest Use of p-sympathomimetics in heart failure carries the risk of cardiac arrhythmias. 

The heart is innervated by both sympathetic and parasympathetic neurons however, their distribution in the heart is quite different. Postganglionic noradrenergic fibers from the stellate and inferior cervical ganglia innervate the sinoatrial (S-A) node and myocardial tissues of the atria and ventricles. Activation of the sympathetic outflow to the heart results in an increase in rate (positive chronotropic effect), in force of contraction (positive inotropic effect), conduction tissue (positive dro-motropic effect). 

An increase in sympathetic neuronal activity causes an increase in heart rate (positive chronotropic effect, or tachycardia) and an increase in cardiac contractile force (positive inotropic effect) such that the stroke output is increased. Cardiac output, which is a function of rate and stroke output, is thus increased. A physiological increase in sympathetic tone is almost always accompanied by a diminution of parasympathetic vagal tone this allows full expression of the effects of increased sympathetic tone on the activity of the heart. 

The effects of nicotine on the cardiovascular system mimic those seen after activation of the sympathoadrenal system, and they are principally the result of a release of epinephrine and norepinephrine from the adrenal medulla and adrenergic nerve terminals. These effects include a positive inotropic and chronotropic effect on the myocardium as well as an increase in cardiac output. In addition, both systohc and diastolic blood pressures are increased secondary to stimulation of the sympathoadrenal system. These effects are the end result of a summation of adrenergic and chohnergic stimulation. 

Chronotropic effect negative. Ethanol (50%) extract of the fresh leaf, administered by gastric intubation to rats at a dose of 40 mL/kg, produced weak activity. Results were significant at p < 0.05 level ". Glycerin/ ethanol extract of the fresh leaf, administered intragastrically to dogs at a dose of 20 mg/kg, produced an increase in length of sinusal cycle (16%), sinoatrial conduction time (27%), and sinus node recovery time (31%) . 

Chronotropic effect positive. Glycerin/ ethanol extract of the leaf and seed oil, administered intragastrically to desoxycorti-costerone acetate-induced hypertensive rats at doses of 500 and 125 mg/kg, respectively, was active " . 

Chronotropic effect negative. Ethanol (50%) extract of the fresh leaf, administered intragastrically to rats at a dose of 40 mg/kg, was active L... 

Dopexamine reduces afterload via 32 and DAI activation and consequent renal and splanchnic vasodilatation. The 31 activity and inhibition of noradrenaline re-uptake are responsible for its positive inotropic and chronotropic effects. It also promotes naturesis (DAI). 

Ephedrine has positive inotropic and chronotropic effects and increases peripheral vascular resistance. It is preferable to methoxamine for maintaining blood pressure in elderly patients during spinal anaesthesia, possibly because it has less effect on coronary blood flow (less pronounced a activity). It is also less likely to impair placental blood flow than some other vasopressors, for the same reason. It is used as a bronchodilator because of its 32-agonist effects. 

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