Calcium sensitivity enhancers.
Patients suffering from acute decompensated heart failure, immediately after infarction, or late in the progression of heart failure, need short-term, positive inotropic support in their therapy. To date, drugs acting through cAMP are used to increase the contractile force of the heart of such patients, although it is well-known that these kind of drugs may trigger arrhythmias and as a result may worsen the long-term prognosis of the patients. Recently, levosimendan, a new drug acting through calcium sensitization of contractile proteins, has shed new light on inotropic therapy, and, importantly, has reduced mortality in acute heart failure patients. For this reason, this review focuses on calcium sensitizers and the mechanisms behind calcium sensitization. The compounds which have been selected for detailed consideration are limited only to positive inotropic compounds that produce calcium sensitization of contractile proteins. In addition, this review elucidates the differences between various calcium sensitizing mechanisms, and mainly focuses on the relaxation of cardiac muscle.
Haikala
H
H
Drug Discovery & Pharmacology, Orion Pharma, Preclinical & Clinical R&D, PO Box 65, FIN-02101 Espoo, Finland. heimo.haikala@orionpharma.com
Pollesello
P
P