Acute heart failure: inotropic agents and their clinical uses

Abstract

Inotropic agents are indispensable for the improvement of cardiac contractile dysfunction in acute or decompensated heart failure. Clinically available agents, including sympathomimetic amines (dopamine, dobutamine, noradrenaline) and selective phosphodiesterase-3 inhibitors (amrinone, milrinone, olprinone and enoximone) act via cAMP/protein kinase A (PKA)-mediated facilitation of intracellular Ca²⁺ mobilisation. Phosphodiesterase-3 inhibitors also have a vasodilatory action, which plays a role in improving haemodynamic parameters in certain patients, and are termed inodilators. The available inotropic agents suffer from risks of Ca²⁺ overload leading to arrhythmias, myocardial cell injury and ultimately, cell death. In addition, they are energetically disadvantageous because of an increase in activation energy and cellular metabolism. Furthermore, they lose their effectiveness under pathophysiological conditions, such as acidosis, stunned myocardium and heart failure. Pimobendan and levosimendan (that act by a combination of an increase in Ca²⁺ sensitivity and phosphodiesterase-3 inhibition) appear to be more beneficial among existing agents. Novel Ca²⁺ sensitisers that are under basic research warrant clinical trials to replace available inotropic agents.

Keywords::

• Ca²⁺ mobilisers
• Ca²⁺ sensitisers
• cardiac E–C coupling
• levosimendan
• phosphodiesterase-3 inhibitors
• pimobendan
• sympathomimetic agents

Notes