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Cardiovascular physiology

Inotropes

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[box type=”download”]  Effect of noradrenaline on calcium handling via beta-receptors  Effects of digoxin (via Na pump) and of hypoxia (H/Ca competition) on calcium handling[/box]

Regulation of contractility: inotropic agents

Sympathetic – increases cardiac muscle contractility by releasing noradrenaline, a positive inotrope. Noradrenaline binds to β1-adrenoceptors causing increased Ca2+ entry via L-type Ca2+ channels during the AP, and thus Ca2+ release from the SR.
Noradrenaline also accelerates Ca2+ sequestration into the SR.
The contractility is also increased by slowing the removal of Ca2+ from the myocyte.

Cardiac glycosides (e.g. digoxin) inhibit the Na+ pump which removes Na+ from the cell decreasing the Na+ gradient across the membrane.
This depresses Na+–Ca2+ exchange, and Ca2+ is pumped out of the cell less rapidly.
Consequently, more Ca2+ is available inside the myocyte for the next beat, and force increases.

Acidosis (blood pH < 7.3) is negatively inotropic, largely because H+ competes for Ca2+-binding sites.