Toward safe inotropic therapy.
The use of currently available positive inotropic agents is associated with an unfavorable clinical outcome. The disappointment with positive inotropic therapy is to some extent foreseeable as currently available inotropic agents may precipitate ventricular arrhythmias due to a diastolic rise in intracellular [Ca], trigger/worsen myocardial ischemia due to an increased oxygen demand, and foster fuel deprivation from an energy starved heart. Safe use of presently available inotropic agents and development of novel inotropic agents must ensure that they are not associated with a diastolic rise in intracellular [Ca], an increase in myocardial oxygen consumption, and energy expenditure. Agents that improve left ventricular systolic performance through prolongation of left ventricular ejection time and not through increased myocardial contractility, that is, myosin activators, may be associated with a favorable outcome as they do not affect diastolic intracellular [Ca], myocardial oxygen demand, and presumably fuel expenditure.
*Division of Cardiology, University of Texas, Houston, TX; †Division of Cardiology, Centre Hospitalier Universitaire de Grenoble, France; and ‡Department of Cardiology, Tulane University Medical School, New Orleans, LA.
Indranee N
IN
Rajapreyar
Pierre V
PV
Ennezat
Thierry H
TH
Le Jemtel
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015316:Genetic Therapy; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects / Q000235:genetics; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D016277:Ventricular Function, Left / Q000187:drug effects
D002316:Cardiotonic Agents; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C506946:ATP2A2 protein, human; D002118:Calcium