Inotropes and Inodilators for Acute Heart Failure

Abstract

Abstract:Acute heart failure (AHF) emerges as a major and growing epidemiological concern with high morbidity and mortality rates. Current therapies in patients with acute heart failure rely on different strategies. Patients with hypotension, hypoperfusion, or shock require inotropic support, whereas diuretics and vasodilators are recommended in patients with systemic or pulmonary congestion. Traditionally inotropic agents, referred to as Ca2+ mobilizers load the cardiomyocyte with Ca2+ and thereby increase oxygen consumption and risk for arrhythmias. These limitations of traditional inotropes may be avoided by sarcomere targeted agents. Direct activation of the cardiac sarcomere may be achieved by either sensitizing the cardiac myofilaments to Ca2+ or activating directly the cardiac myosin. In this review, we focus on sarcomere targeted inotropic agents, emphasizing their mechanisms of action and overview the most relevant clinical considerations.

Probenecid Improves Cardiac Function in Patients With Heart Failure With Reduced Ejection Fraction In Vivo and Cardiomyocyte Calcium Sensitivity In Vitro

“…Available therapies to improve myocardial contractility are limited to digoxin and parenteral inotropes (ie, isoproterenol, dobutamine, and milrinone) 2, 3. Most parenteral inotropes share the common end point of increasing cAMP levels in the cardiomyocyte leading to increased calcium influx into the cell that in turn stimulates myocyte contractility 4. Cardiomyocyte loading of calcium increases myocardial contractile force, oxygen consumption, and apoptotic signaling 5, 6, 7.…”

Inotropes and vasopressors

“…Vasodilation is caused by decreasing the myofilaments sensitivity in smooth muscles to calcium and by activating ATP-dependent potassium channels which results in hyperpolarization, decreased Ca2+entry and vasodilation (16). These effects occur without an increase in intracellular cAMP or calcium (29,30). Therefore, it does not impair diastolic relaxation and cardiac rhythm (1,30).…”

“…These effects occur without an increase in intracellular cAMP or calcium (29,30). Therefore, it does not impair diastolic relaxation and cardiac rhythm (1,30). It has beneficial effects on myocardial energetics as its effects occur without an increase in myocardial oxygen consumption (30).…”

“…It is administered at infusion rates of 0.05-0.6 μg/ kg/min (14,29). At rates higher than 0.2 μg/kg/min, there is a greater incidence of side effects such as headache, nausea and hypotension (30). In case of significant hypotension, use of norepinephrine or vasopressin is recommended (16).…”

“…Therefore, it does not impair diastolic relaxation and cardiac rhythm (1,30). It has beneficial effects on myocardial energetics as its effects occur without an increase in myocardial oxygen consumption (30). Anti-inflammatory effects of levosimendan are manifested as areduction of circulating proinflammatory cytokines and reduction of mediators of apoptosis (31).…”