Inotropic agents in the treatment of heart failure: despair or hope?
Depression of myocardial contractility plays an important role in the development of heart failure; therefore, intensive interest and passion have been generated to develop cardiotonic agents to improve the contractile function of the failing heart. Inotropic agents that increase cyclic AMP, either by increasing its synthesis or reducing its degradation, exert dramatic short-term hemodynamic benefits, but these acute effects cannot be extrapolated into long-term improvement of the clinical outcome in patients with advanced heart failure. Administration of these agents to an energy-starved failing heart would be expected to increase myocardial energy use and could accelerate disease progression. The role of digitalis in the management of heart failure has been controversial, but ironically the drug has now been proved to favorably affect the neurohormonal disorders and its reevaluation is now being intensively investigated. More recently, attention has been focused on other inotropic agents that have a complex and diversified mechanism. Recent clinical studies have demonstrated that they are potentially useful in the long-term treatment of heart failure patients. These agents have some phosphodiesterase-inhibitory action but also possess additional effects, including acting as cytokine inhibitors, immunomodulators, or calcium sensitizers. However, their therapeutic ratio is narrow and further studies are warranted to establish their optimal doses and their eventual status in the treatment of heart failure.
Sasayama
S
S
Department of Cardiovascular Medicine, Kyoto University, Japan.
D000318:Adrenergic beta-Agonists / Q000627:therapeutic use; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism*; D004070:Digitalis; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D010946:Plants, Medicinal; D010947:Plants, Toxic; D011379:Prognosis; D011719:Pyrazines; D011724:Pyridazines / Q000627:therapeutic use; D011804:Quinolines / Q000627:therapeutic use
D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D011719:Pyrazines; D011724:Pyridazines; D011804:Quinolines; C041648:pimobendan; C041667:vesnarinone; D000242:Cyclic AMP