Contractility, cardiac

Halogenated hydrocarbons depress cardiac contractility, decrease heart rate, and inhibit conductivity in the cardiac conducting system. The cardiac-toxicity of these compounds is related to the number of halogen atoms it increases first as the number of halogen atoms increases, but decreases after achieving the maximum toxicity when four halogen atoms are present. Some of these compounds, e.g., chloroform, carbon tetrachloride, and trichloroethylene, sensitize the heart to catecholamines (adrenaline and noradrenaline) and thus increase the risk of cardiac arrhythmia. 

Relatively selective stimulation of Pi-adrenergic receptors can be achieved with dobutamine. This is a racemic drug of which both isomers activate the Pi-receptor, and in addition the (-) isomer activates ( -receptors whereas the (+) isomer activates p2-receptors the simultaneous activation of ai- and p2-receptors results in no major net effect on peripheral resistance, and thus the overall cardiovascular effects are mediated by Pi-stimulation leading to increases in cardiac contractility and output. Dobutamine is used for the short-term treatment of acute cardiac failure and for diagnostic purposes in stress echocardiography. 

Apelins and the Apelin Receptor. Figure 3 Scheme illustrating the hypothesised mechanisms of control of human (a) vasculartone and (b) cardiac contractility by apelin peptides ( ). In the vasculature, apelins (released via the small vesicles of the constitutive pathway) may act directly to activate apelin receptors on the underlying smooth muscle to produce vasoconstriction. This response may be modified by apelin peptides feeding back onto apelin receptors on endothelial cells to stimulate the release of dilators, such as nitric oxide. In heart, apelin peptides, released from endocardial endothelial cells, activate apelin receptors on cardiomyocytes to elicit positive inotropic actions. 

Sorcin is associated with the development of multidrug resistances in leukemia and other cancels. Sorcin is also able to improve cardiac contractility independently of (3-adienergic stimulation and may prove beneficial in treatment of heart failure. A point mutation in sorcin causes familial hypertrophic cardiomyopathy. 

Ca2+ is an important intracellular second messenger that controls cellular functions including muscle contraction in smooth and cardiac muscle. Ca2+ channel blockers inhibit depolarization-induced Ca2+ entry into muscle cells in the cardiovascular system causing a decrease in blood pressure, decreased cardiac contractility, and antiarrhythmic effects. Therefore, these drugs are used clinically to treat hypertension, myocardial ischemia, and cardiac arrhythmias. 

Peripheral mAChRs are known to mediate the well-documented actions of ACh at parasympathetically innervated effector tissues (organs) including heart, endocrine and exocrine glands, and smooth muscle tissues [2, 4]. The most prominent peripheral actions mediated by activation of these receptors are reduced heart rate and cardiac contractility, contraction of... 

Bers, D.M. (1991). Excitation-Contraction Coupling and Cardiac Contractile Force . Kluwer Academic Publishers, Dordrecht. 

The determinants of oxygen supply and demand are shown in Fig. 4-1. Increases in heart rate, left ventricular wall tension, and cardiac contractility increase the rate of myocardial... 

Anti-anginal Agent Heart Rate Wall Tension Cardiac Contractility Oxygen Supply... 

Consequences of metabolic acidosis include renal bone disease, reduced cardiac contractility, predisposition to arrhythmias, and protein catabolism. 

Babiychuk EB, Draeger A 2000 Annexins in cell membrane dynamics. Ca2+-regulated association of lipid microdomains. J Cell Biol 150 1113-1124 Ber DM 2001 Excitation-contraction coupling and cardiac contractile force, 2nd edn. Kluwer Academic Publishers, Dordrecht/Boston/London Blaustein MP, Golovina VA 2001 Structural complexity and functional diversity of endoplasmic reticulum Ca2+ stores. Trends Neurosci 24 602—608 Flynn ER, Bradley KN, Muir TC, McCarron JG 2001 Functionally separate intracellular Ca2+ stores in smooth muscle. J Biol Chem 276 36411-36418 Fry CH, WuCl 997 Initiation of contraction in detrusor smooth muscle. Scand J Urol Nephrol Suppl 184 7-14... 

Compounds CI-914 and CI-930 have been reported to produce dose-related increases in cardiac contractile force at doses of 0.01-1.0 mg/kg and... 

The choice between calcium antagonists must take into account the differential effect of nifedipine versus verapamil or diltiazem on cardiac performance (see above). When p-blockers are given, the potential consequences of reducing cardiac contractility (withdrawal of sympathetic drive) must be kept in mind. Since vasodilating P2-receptors are blocked, an increased risk of vasospasm cannot be ruled out Therefore, monotherapy with p-blockers is recommended only in angina due to coronary sclerosis, but not in variant angina. 

In addition to being used as antianginal and antiarrhythmic agents, calcium channel blockers are used to treat weak and moderate hypertension. These drugs prevent calcium ions from entering into the smooth muscle cells of peripheral vessels, and they cause relaxation of peripheral vessels, which leads to lowering of arterial blood pressure. In clinically used doses, calcium channel blockers relax smooth musculature of arteries and have little effect on veins. In doses that relax smooth musculature, calcium channel blockers have relatively little effect on cardiac contractility. 

Pharmacology Calcium is essential for the functional integrity of the nervous and muscular systems, for normal cardiac contractility and the coagulation of blood. It also functions as an enzyme cofactor and affects the secretory activity of endocrine and exocrine glands. 

Verapamil and a few newer dmgs of this category are vasodilator agents, which in addition impair AV conduction, reduce heart rate and cardiac contractile force. Verapamil was initially developed for the treatment of supraventricular tachycardia and it continues to be an important drug for the management of this condition, also postoperatively. Verapamil is the CA of choice in the management of hypertrophic cardiomyopathy. Verapamil is also used in the treatment of stable angina and, less frequently, essential hypertension. 

Dihydropyridine-CA have been developed with a certain degree of vascular selectivity, which implies that at therapeutic doses such compounds would have less negative influence on cardiac contractile force or none at all. Indeed, a few of such compounds are devoid of cardiodepressant (negative inotropic) activity. Examples of such compounds are amlodipine, felodipine, isradip-ine, lacidipine, lercanidipine and manidipine. 

Isoprenaline, a.fii+ jS2-receptor agonist, is sometimes used in paediatric cardiac surgery. It causes a rise in cardiac contractile force and heart rate (both via /3i) as well as vasodilatation (jS2-effect). 

The enzyme phosphodiesterase (type III) catalyzes the biode-gradation of cyclic AMP (cAMP). Inhibition of this enzyme will cause accumulation of the nucleotide cAMP and hence induces an increase in cardiac contractile force. This effect does not involve cardiac jS-adrenoceptors and will therefore persist after downregulation of these receptors associated with heart failure. 

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. 

Although myocardial depression is not a problem in patients with normal cardiac function, in patients with compromised myocardial function, quinidine may depress cardiac contractility sufficiently to result in a de-... 

The toxicity associated with propranolol is for the most part related to its primary pharmacological action, inhibition of the cardiac (3-adrenoceptors. This topic is discussed in detail in Chapter 11. In addition, propranolol exerts direct cardiac depressant effects that become manifest when the drug is administered rapidly by the IV route. Glucagon immediately reverses all cardiac depressant effects of propranolol, and its use is associated with a minimum of side effects. The inotropic agents amrinone (Inocor) and milrinone (Primacor) provide alternative means of augmenting cardiac contractile function in the presence of -adrenoceptor blockade (see Chapter 15). Propranolol may also stimulate bron-chospasm in patients with asthma. 

Because of the extensive presence of )Si-ARs in the non-failing myocardium, the heart can be defined as a jSi-AR organ. The )Si// 2-AR ratio within the ventricles of the healthy human heart is 80/20 and the average jS-AR density (Bmax) in atria and ventricles is normally 70-100 fmol/mg protein [89], In the heart, Pt-AR agonists are responsible for the increase in cardiac contractility and heart rate, whereas bronchodilation and vasodepression can be mediated by / 2-selective agonists. 

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