Contractile force, heart

The cardiac effects of the calcium antagonists, ie, slowed rate (negative chronotropy) and decreased contractile force (negative inotropy), are prominent in isolated cardiac preparations. However, in the intact circulation, these effects may be masked by reflex compensatory adjustments to the hypotension that these agents produce. The negative inotropic activity of the calcium antagonists may be a problem in patients having heart failure, where contractility is already depressed, or in patients on concomitant -adrenoceptor blockers where reflex compensatory mechanisms are reduced. 

Verapamil (Table 1), the first slow channel calcium blocker synthesized to selectively inhibit the transmembrane influx of calcium ions into cells, lowers blood pressure in hypertensive patients having good organ perfusion particularly with increased renal blood flow. Sustained-release verapamil for once a day dosing is available for the treatment of hypertension. Constipation is a prominent side effect. Headache, dizziness, and edema are frequent and verapamil can sometimes cause AV conduction disturbances and AV block. Verapamil should not be used in combination with -adrenoceptor blockers because of the synergistic negative effects on heart rate and contractile force. 

Cardiovascular effects Harmala alkaloids have cardiovascular effects (Aarons et al. 1977). Harmine, harmaline, and harmalol decrease heart rate, but increase pulse pressure, peak aortic flow, and myocardial contractile force in dogs. Harmine reduces systemic arterial blood pressure and peripheral vascular resistance. Vascular resistance effects are not mediated by jS-adrenergic or histamine HI receptors. 

A second assay which has been used extensively in the characterization of 5-HT3 receptors is the rabbit isolated heart. Both the sympathetic and parasympathetic inputs to the rabbit heart can be influenced by stimulation of 5-HT3 receptors this preparation is usually performed in the presence of atropine to block parasympathetic effects [12]. Under these conditions, 5-HT and other 5-HT3 receptor agonists exert positive effects on rate and contractile force. Selective 5-HT3 receptor antagonists such as MDL 72222 [6], ICS 205-930 [3] and ondansetron [7] block the agonist effects in a concentration-related manner. 

An isolated mammalian heart whose extrinsic nervous connections have been severed will beat spontaneously for hours if it is supplied with a nutrient medium via the aortic trunk and coronary arteries (Langendorff preparation). In such a preparation, only those drugs that act directly on cardio-myocytes will alter contractile force and beating rate. 

Diverse plants (A) are sources of sugar-containing compounds (glycosides) that also contain a steroid ring (structural formulas, p. 133) and augment the contractile force of heart muscle (B) cardiotonic glycosides, cardiosteroids, or digitalis."... 

Factors determining oxygen demand. The heart muscle cell consumes the most energy to generate contractile force. O2 demand rises with an increase in (1) heart rate, (2) contraction velocity, (3) systolic wall tension ( afterload ). The latter depends on ventricular volume and the systolic pressure needed to empty the ventricle. As peripheral resistance increases, aortic pressure rises, hence the resistance against which ventricular blood is ejected. O2 demand is lowered by 3-blockers and Ca-antago-nists, as well as by nitrates (p. 308). 

In the area perfused by the affected vessel, inadequate supply of oxygen and glucose impairs the function of heart muscle contractile force declines. In the great majority of cases, the left ventricle (anterior or posterior wall) is involved. 

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. 

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. 

In summary, cardiac glycosides increase contractile force and reduce heart rate and AV conduction. In addition, cardiac glycosides suppress the sympathetic hyperactivity which occurs in advanced stages of congestive heart failure via a complex mechanism involving the central nervous system. 

Activation of aj-adrenoceptors in smooth muscle of blood vessels leads to vasoconstriction, while activation of Pj-adrenoceptors in blood vessels of skeletal muscle produces vasodilation. Activation of Pi-adrenoceptors on cardiac tissue produces an increase in the heart rate and contractile force. 

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 net effect of norepinephrine administration on heart rate and ventricular contractile force therefore varies with the dose of norepinephrine, the physical activity of the subject, any prior cardiovascular and baroreceptor pathology, and the presence of other drugs that may alter reflexes. 

The cardiac effects of epinephrine are due to its action on p-adrenoceptors in the heart. The rate and contractile force of the heart are increased consequently, cardiac output is markedly increased. Because total peripheral resistance is decreased, the increase in cardiac output is largely responsible for the increase in systolic pressure. Since epinephrine causes little change in the... 

Ephedrine increases systolic and diastolic blood pressure heart rate is generally not increased. Contractile force of the heart and cardiac output are both increased. Ephedrine produces bronchial smooth muscle relaxation of prolonged duration when administered orally. Aside from pupillary dilation, ephedrine has little effect on the eye. 

C. Nitroglycerin can increase heart rate via an increase in sympathetic tone to the heart due to an excessive decrease in blood pressure propranolol would block the p-receptors responsible for the tachycardia. Propranolol does not decrease preload, and its effect to decrease afterload would exacerbate the decrease in afterload produced by nitroglycerin. Propranolol does not increase myocardial contractile force and could actually increase the incidence of vasospasm by unmasking a-adrenocep-tors in the coronary blood vessels. 

Angiotensin II stimulates the influx of Ca" " into cardiac muscle cells and can exert a direct inotropic effect at cardiac muscle. In addition, angiotensin II can stimulate the sympathoadrenal system and thereby increase myocardial contractility. In contrast to its effects on vascular smooth muscle, the ability of angiotensin to increase the contractile force of the heart is far less potent. Therefore, in spite of the positive chronotropic and inotropic effects produced by angiotensin II, cardiac output is rarely increased. In fact, angiotensin II may decrease cardiac output through reflex bradycardia induced by the rise in peripheral resistance that it causes. In contrast, centrally administered angiotensin II increases both blood pressure and cardiac output. 

Theophylline, given as the soluble ethylenediamine salt aminophylline, offers some help in relieving the paroxysmal dyspnea that is often associated with left heart failure. A major portion of its efficacy may be due to the relief of bronchospasm secondary to pulmonary vascular congestion. Theophylline increases myocardial contractile force and has occasionally been used in the treatment of refractory forms of congestive heart fail-... 

Acting as an intracellular second messenger, cAMP mediates such hormonal responses as the mobilization of stored energy (the breakdown of carbohydrates in liver or triglycerides in fat cells stimulated by B-adrenomimetic catecholamines), conservation of water by the kidney (mediated by vasopressin), Ca2+ homeostasis (regulated by parathyroid hormone), and increased rate and contractile force of heart muscle ( -adrenomimetic catecholamines). It also regulates the production of adrenal and sex steroids (in response to corticotropin or follicle-stimulating hormone), relaxation of smooth muscle, and many other endocrine and neural processes. 

Early evidence that prejunctional histamine H3-receptors may modulate the sympathetic nerve activity on the heart was provided by Luo et al., (1991). These authors clearly stated that the selective H3-agonist (R)a-methylhistamine attenuates the inotropic response induced by transmural stimulation of the adrenergic nerve terminals in the isolated right atrium, without affecting basal contractile force of the preparation or the positive inotropic effect elicited by exogenous noradrenaline. The effect of (R)a-methylhistamine, which is not modified by Hi and H2-receptor blockade, was reversed by the specific H3-receptor antagonist thioperamide, at concentrations which do not influence the inhibitory activity mediated by other presynaptic receptors, like a2-adrenoceptors. 

The use of Coleus Forskohlii seems to have possible cardiovascular benefits by acting as a vasodilator (lowers blood pressure), inhibition of platelet aggregation (reduced blood clotting), and positive inotropic activity in the heart (increased contractile force). 

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