Could Ca2+ sensitizers rescue patients from chronic congestive heart failure?
Attempts to ameliorate cardiac contractile dysfunction by Ca(2+) mobilizers, such as catecholamines, phosphodiesterase (PDE) inhibitors and digitalis, play an important role in pharmacotherapy for congestive heart failure (CHF), but these agents possess disadvantages in causing Ca(2+) overload resulting in arrhythmogenicity and damage to cardiomyocytes. Ca(2+) sensitizers that act directly on contractile proteins are free from the risk of Ca(2+) overload and they could improve haemodynamic parameters with minimum increase in energy expenditure even under pathological conditions, including acidosis and stunned myocardium. Beneficial effects of levosimendan (that acts by combination of Ca(2+) sensitization and PDE inhibition) on CHF due to hypertensive cardiomyopathy in Dahl/Rapp rats as reported in this issue demonstrate the potential of oral levosimendan in long-term treatment of chronic CHF. Since chronic CHF in clinical settings is much more complex, careful analysis of clinical outcomes will be required to establish the therapeutic relevance of Ca(2+) sensitizers in the treatment of chronic CHF.
Endoh
M
M
Department of Cardiovascular Pharmacology, Yamagata University School of Medicine, Yamagata, Japan. mendou@med.id.yamagata-u.ac.jp
D000818:Animals; D002118:Calcium / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy*; D006801:Humans; D006835:Hydrazones / Q000494:pharmacology / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D011724:Pyridazines / Q000494:pharmacology / Q000627:therapeutic use*; D000077464:Simendan
D002316:Cardiotonic Agents; D006835:Hydrazones; D010726:Phosphodiesterase Inhibitors; D011724:Pyridazines; D000077464:Simendan; D002118:Calcium