Is calcium sensitization the best strategy to improve myocardial contractility in acute heart failure?
The finely-tuned increases and decreases in the intracellular calcium levels in myocytes ultimately regulate the contraction and relaxation of the heart. Therapeutic agents can improve or interfere with this delicate balance. Calcium sensitizers enhance cardiac contraction by improving the use of calcium that is available, rather than by inundating the cell with excessive calcium, as is the case with traditional inotropes. With the sensitizing mechanism, the energy cost of contraction is maintained at a near-normal level, and the threat of arrhythmias and sudden death is low. Levosimendan is the first calcium sensitizer to become available for the treatment of patients with acute heart failure. In recent clinical studies, levosimendan increased cardiac output and stroke volume without significantly increasing oxygen demand. By its additional action as a vasodilator (via potassium channel opening), levosimendan also corrects the hemodynamic decompensation, thus lowering the pulmonary capillary wedge pressure and systemic vascular resistance. Furthermore, levosimendan increases the coronary circulation thus leading to an improved function of the stunned myocardium and lessened ischemia. Taken together, levosimendan's primary calcium-sensitizing action, along with its complementary vasodilator properties, make this new drug a highly promising agent for the treatment of patients with acute heart failure.
Erhardt
Leif R
LR
Department of Cardiology, Cardiology Research Unit, Malmo University Hospital, 205 02 Malmo, Sweden. Leif.Erhardt@medforsk.mas.lu.se
D000208:Acute Disease; D002118:Calcium / Q000502:physiology*; D020746:Calcium Channels, L-Type / Q000627:therapeutic use*; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D011724:Pyridazines / Q000627:therapeutic use; D000077464:Simendan; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use
D020746:Calcium Channels, L-Type; D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D000077464:Simendan; D002118:Calcium