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Updated: Jul 19, 2026

Contractility Measurements on Isolated Papillary Muscles for the Investigation of Cardiac Inotropy in Mice
Published on: September 17, 2015
Acute heart failure: inotropic agents and their clinical uses
1Department of Cardiovascular Pharmacology, Yamagata University School of Medicine, Yamagata, 2-2-2 Iida-nishi, 990-9585, Japan. mendou@med.id.yamagata-u.ac.jp
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.
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