Inotropic agents and immune modulation.
Since depression of myocardial contractility forms the basis for the development of heart failure, many attempts have been made to enhance the inotropic state of the failing heart by cardiotonic agent as the therapeutic modality. However, large scale clinical trials conducted in the Western societies revealed excess mortality in patients with heart failure received long-term treatment with inotropic agent. Therefore, all of these agents are now regarded as unsuitable for chronic heart failure treatment. In contrast, some inotropic agents with phosphodiesterase inhibitory properties exhibited potential benefits in Japanese patients. In Japan mortality due to heart disease is substantially lower than that found in all other Western countries. Thereby, chronic treatment with inotropic agent may be justified as the optimal care in the context of relief of symptoms and an improved quality of life. The salutary effects of these phosphodiesterase inhibitors appear to be related to anticytokine and immunomodulating effects as well as their cardiotonic action. These findings support the recent new concept that immune responses mediated by cytokines play an important role in the pathogenesis of heart failure.
Sasayama
Shigetake
S
Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan. sasayama@wonder.ocn.ne.jp
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000037:antagonists & inhibitors; D006333:Heart Failure / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D006801:Humans; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011719:Pyrazines; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use; D011788:Quality of Life; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors
D000276:Adjuvants, Immunologic; D002316:Cardiotonic Agents; D016207:Cytokines; D010726:Phosphodiesterase Inhibitors; D011719:Pyrazines; D011724:Pyridazines; D011804:Quinolines; C041648:pimobendan; C041667:vesnarinone