Title:A Review on Role of the Calcium Sensitive Inotropic Agent, Levosimendan and Its Metabolites
Volume: 18
Issue: 16
Author(s): Mohammad Asif*
Affiliation:
- GRD (PG) Institute of Management and Technology, Dehradun,India
Keywords:
Heart failure, levosimendan, calcium sensitizer, troponin-C, calmodulin, inotropic.
Abstract: Levosimendan is a pyridazinone-dinitrile derivative, emerged as a potent cardiotonic agent
with dual inotropic and vasodilator activities in higher animals. This is a calcium (Ca2+) sensitizing
cardiotonic agent, which has been shown to exert positive inotropic effects without increasing intracellular
Ca2+ transient. This avoids Ca2+ overload that leads to arrhythmias and myocyte injuries, and do
not increase the energy consumption for handling Ca2+ and has shown good activity against congestive
heart failure (CHF), due to its increased myocardial contractility by stabilizing the calcium bound conformation
of troponin C. Levosimendan also acts as a pulmonary and systemic vasodilator. The combination
of positive inotropic and vasodilator activity has been beneficial in increasing cardiac output
and decreasing left ventricular end-diastolic pressure, pulmonary wedge pressure, right atrial pressure,
and systemic vascular resistance in CHF patients. The cardiac target protein of levosimendan and troponin
C, is Ca2+-binding protein. This raises the possibility that levosimendan may interact with
smooth muscle proteins, such as, calmodulin, and regulatory myosin light chains. Levosimendan relaxes
coronary arteries and lowers Ca2+. The lowering of Ca2+ by levosimendan is consistent with
opening of K+ channels and causes relaxation that is independent of Ca2+. However, most of the Ca2+
sensitizers may impair cardiac diastolic function as a result of increased Ca2+ sensitivity of the myofilaments.
Levosimendan has not only improved the cardiac systolic function but also the diastolic relaxation
in CHF.
