Fropofol decreases force development in cardiac muscle

What is it about?

Certain heart diseases are characterized by increased contractility (such as hypertrophic cardiomyopathy), and inhibiting force generation will be treatment of choice. However, there are no such direct myofilament depressing agents available at present. This is the first study investigating fropofol, a novel small molecule propofol derivative without anesthetic potency, on myocardial contraction. In isolated rat normal cardiac trabecular muscles and muscles with increased contractility, fropofol decreased force development without affecting intracellular Ca2+. Furthermore, we have shown that fropofol is a direct myofilament desensitizer/inhibitor by providing the first evidence of its cross-bridge interaction including force development, myofilament ATPase activity, actin-activated myosin ATPase activity, and myosin sliding velocity over actin. Fropofol did not affect contraction in skeletal muscle. From a clinical standpoint, these findings are particularly significant given that fropofol is a nonanesthetic small molecule that decreases myocardial contractility specifically and, thus, may be useful in the treatment of hypercontractile cardiac disorders. Therefore, the results of this study pave the way for fropofol to be tested in preclinical studies in disease models of hypertrophic cardiomyopathy.

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