Chronotropic effect

Kaumann, A. J., and Marano, M. (1982). On equilibrium dissociation constants for complexes of drag receptor subtypes Selective and nonselective interactions of partial agonists with two P-adrenoceptor subtypes mediating positive chronotropic effects of (-) isoprenaline in kitten atria. Nannyn Schmiedebeberg s Arch. Pharmacol. 219 216—221. 

Closely monitor heart rate in patients treated with drugs that have negative chronotropic effects (e.g., fi-blockers, verapamil, or diltiazem) or drugs that may cause reflex tachycardia (e.g, nitrates or dihydropyridine CCBs). 

Vasopressin levels are increased during hypotension to maintain blood pressure by vasoconstriction. However, there is a vasopressin deficiency in septic shock. Low doses of vasopressin increase MAP, leading to the discontinuation of vasopressors. However, routine use of vasopressin is not recommended because of lack of evidence of efficacy. Vasopressin is a direct vasoconstrictor without inotropic or chronotropic effects and may result in decreased cardiac output and hepatosplanchnic flow. Vasopressin use may be considered in patients with refractory shock despite adequate fluid resuscitation and high-dose vasopressors.24,27-28... 

Figure 14.1 Effect of autonomic nervous system stimulation on action potentials of the sinoatrial (SA) node. A normal action potential generated by the SA node under resting conditions is represented by the solid line the positive chronotropic effect (increased heart rate) of norepinephrine released from sympathetic nerve fibers is illustrated by the short dashed line and the negative chronotropic effect (decreased heart rate) of acetylcholine released from parasympathetic nerve fibers is illustrated by the long dashed line.

The vascular endothelium produces a number of substances that are released basally into the blood vessel wall to alter vascular smooth muscle tone. One such substance is endothelin (ET-1). Endothelin exerts its effects throughout the body, causing vasoconstriction as well as positive inotropic and chronotropic effects on the heart. The resulting increases in TPR and CO contribute to an increase in MAP. Synthesis of endothelin appears to be enhanced by many stimuli, including Ag II, vasopressin, and the mechanical stress of blood flow on the endothelium. Synthesis is inhibited by vasodilator substances such as prostacyclin, nitric oxide, and atrial natriuretic peptide. There is evidence that endothelin is involved with the pathophysiology of many cardiovascular diseases, including hypertension, heart failure, and myocardial infarction. Endothelin receptor antagonists are currently available for research use only. 

More recently, the clavulones (not specified which ones) [134] were described to have potent effects on the spontaneous beating rate of cultured myocardial cells from fetal mouse hearts. At a concentration of 0.45 pM, clavulone had positive chronotropic action on these cells however, the character of this effect clearly differed from the positive ionotropic and negative chronotropic effects of the steroid glycoside ouabain or the drug Bay K 8644. Hence, these results suggest that the clavulones may possess a new mechanism of action in this assay system. 

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. 

Sugiyama, A., Kobayashi, M., Tsujimoto, G., Motomura, S., and Hashimoto, K., The first demonstration of CGRP-immunoreactive fibers in canine hearts coronary vasodilator, inotropic and chronotropic effects of CGRP in canine isolated, blood-perfused heart preparations, Jpn. J. Pharmacol, 50, 421-427, 1989. 

Lorenzo PS, Rubio MC, Medina JH, Adler-Graschinsl E. (1996). Involvement of monoamine oxidase and noradrenaline uptake in the positive chronotropic effects of apigenin in rat atria. EurJ Pharmacol. 312(2) 203-7. 

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. 

About scaritoxin, the following results were reported. This toxin was found to depress the oxidative metabolic process in the rat brain (20) and to have a depolarizing action on excitable membranes (38). In the guinea-pig atria, scaritoxin caused a marked potentiation of the acetylcholine negative inotropic and chronotropic effects (39). In rat atria, we observed biphasic inotropic and chronotropic effects similar to those of ciguatoxin. Negative inotropic and chronotropic effects were antagonized by atropine. 

Action on the CNS depends directly on the dose of administered drug, and can be manifested as fatigue, anxiety, tremors, and even convulsions in relatively high doses. Theophylline acts on the cardiovascular system by displaying positive ionotropic and chronotropic effects on the heart, which, can likely be linked to the elevated influx of calcium ions by modulated cyclic adenosine monophosphate and its action on specific cardiac phosphodiesterases. In the gastrointestinal system, methylxanthines simultaneously stimulate secretion of both gastric juice and digestive enzymes. 

Hi-receptors mainly mediate the constriction of large and relaxation of small blood vessels, contractions of the bronchial, intestinal and uterine smooth muscle and contractions of vascular endothelial cells with the result of an increased capillary permeability. The lymphatic flow is augmented by Hi-receptor stimulation. H2-receptor stimulation induce a dilatation of pulmonary arteries, a positive inotropic and chronotropic effect on the heart and an increased glandular secretion, especially in the mucosa of the stomach. 

Atarashi H, Endoh Y, Saitoh H, Kiashida H, Hayakawa H. Chronotropic effects of cilostazol, a new antithrombotic agent, in patients with bradyarrhythmias. J Car-diovasc Pharmacol 1998 31 534-9. 

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. 

Acebutolol reduces blood pressure in patients with essential hypertension primarily through its negative inotropic and chronotropic effects. 

Verapamil must be used with extreme caution or not at all in patients who are receiving p-adrenoceptor blocking agents. Normally, the negative chronotropic effect of verapamil will in part be overcome by an increase in reflex sympathetic tone. The latter is be prevented by simultaneous administration of a p-adrenoceptor blocking agent, which exaggerates the depressant effects of... 

Propranolol and nadolol also have been used successfully in combination with certain calcium entry blockers, particularly nifedipine, for the treatment of secondary angina. Caution should be used, however, when combining a p-blocker and a calcium channel blocker, such as verapamil or diltiazem, since the negative inotropic and chronotropic effects of this combination may lead to severe bradycardia, arteriovenous nodal block, or decompensated congestive heart failure. 

C) Inhibition of a GABA-mediated negative chronotropic effect at the heart... 

In addition to its effects on the vasculature, histamine exerts direct positive inotropic and chronotropic effects on the heart through the stimulation of Hj-receptors. Hj-receptors on sympathetic nerve terminals in the heart decrease norepinephrine release however, this effect appears to be significant only during stress states such as ischemia. 

The postsynaptic S-adrenoceptors (jS-ARs) belong to the rhodopsin/ S2 adrenergic receptor-like receptors that belong to one of three major subfamilies of the GPCRs [83]. The S-AR family is subdivided into at least three discrete subtypes, the ySr, )S2-AR [84], and the atypical jSa-AR [85,86]. Additionally, a putative subtype has been identified in cardiac tissue, classified as the P4-AR [87], The P-]- and S2-AR are Gs-protein coupled, thereby elevating the intracellular level of cyclic adenosine monophosphate (cAMP) and causing positive inotropic and chronotropic effects [88]. The P2-AR can also couple to the Grprotein. 

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 " . 

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