Authors: Lucky Argasetya, Didik Hasmono, Suharjono
Department of Clinical Pharmacy, Faculty of Pharmacy, Airlangga University
Jalan Dharmawangsa Dalam, Surabaya 60286, East Java, Indonesia
email: shj_ms_id@yahoo.com, gwae23@yahoo.com & luckyargasetya@gmail.com
Abstract
Heart failure commonly marked by cardiac systolic dysfunction, associated with the mortality and morbidity that remains high and has few therapeutic advances in decades. Impaired cardiac contractility is a central pathophysiological feature and may be a key therapeutic target. The inotropic agents increase cardiac contractility by altering intracellular calcium flux, but are associated with myocardial ischemia, hypotension, arrhythmias, and mortality. Adverse effects associated with the administration of current inotropic agents have stimulated research and development of novel drugs which would directly target the cardiac sarcomere. Direct activation of the cardiac sarcomere could be achieved in two ways: sensitizing proteins to calcium or activating cardiac myosin directly. A new class of pharmacologic agents, cardiac myosin activators, directly targets the kinetics of the myosin head, an inotropic property resulting in the improvement of systolic function of the heart without increasing energy demand and cellular calcium concentrations. It increases stroke volume, decreases filling pressures, and improves ventricular volumes by increasing the left ventricular systolic ejection time, without increasing the rate of left ventricular pressure development or heart rate, and without noticeable effect upon myocardial oxygen uptake, blood pressure, or coronary blood flow. They still a challenge developing a novel mechanism in heart failure.
Key words: heart failure, cardiac contractility, cardiac myosin activator, inotropic.
