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Thus, the concentration of calcium ions within the cell rises. The effect of increased intracellular calcium ion levels is a more controlled forceful contraction of the myocardium. This is known as a positive inotropic effect. In addition, through an effect in the central nervous system cardiac glycosides cause an increase in parasympathetic activity and therefore slow conduction through the AV node, hence their usefulness in atrial flutter and atrial fibrillation. However, cardiac glycosides have a very low therapeutic ratio and can be very toxic.

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Cardiac output also depends on end systolic volume, which in turn depends on afterload. Afterload is a function of total peripheral vascular resistance and blood pressure. If afterload becomes greater, ESV increases and cardiac output is reduced. As this happens, the EDV also increases and it follows that there is an increase in the force of contraction to restore cardiac output. In either case, the increase in force of contraction results in an increase in cardiac work and oxygen consumption.

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