TY - JOUR
T1 - Istaroxime
T2 - A New Luso-Inotropic Agent for Heart Failure
AU - Mattera, Giovan Giuseppe
AU - Lo Giudice, Pietro
AU - Loi, Francesca M P
AU - Vanoli, Emilio
AU - Gagnol, Jean Pierre
AU - Borsini, Franco
AU - Carminati, Paolo
PY - 2007/1/22
Y1 - 2007/1/22
N2 - Istaroxime is a new luso-inotropic compound selected for the treatment of acute heart failure syndromes, which reduces sodium-potassium adenosine triphosphatase (ATPase) activity and stimulates the sarcoplasmic calcium ATPase isoform 2 reuptake function. The aim of this study was to evaluate the safety profile of istaroxime. For this purpose, istaroxime was administered during a 24-hour infusion to conscious dogs with chronic heart failure and to genetically cardiomyopathic BIO TO.2 hamsters for 34 weeks orally. The parameters recorded were arrhythmic events and hemodynamic effects in dogs and mortality in hamsters. In dogs, istaroxime at 1, 3, and 4 μg/kg per min did not trigger arrhythmic events or magnify preexisting events. It increased left ventricular (LV) dP/dtmax (about 50% at 3 μg/kg per min) and LV - dP/dtmax (about 20% at 3 μg/kg per min) without changing heart rate, blood pressure, or double product. At 4 μg/kg per min, istaroxime increased dP/dtmax >100% but induced intense emesis in all animals. In cardiomyopathic hamsters, the dose of 30 mg/kg prolonged the survival rate to 32%. In conclusion, istaroxime seems to be a promising and safe new drug for improving cardiac performance in the failing heart.
AB - Istaroxime is a new luso-inotropic compound selected for the treatment of acute heart failure syndromes, which reduces sodium-potassium adenosine triphosphatase (ATPase) activity and stimulates the sarcoplasmic calcium ATPase isoform 2 reuptake function. The aim of this study was to evaluate the safety profile of istaroxime. For this purpose, istaroxime was administered during a 24-hour infusion to conscious dogs with chronic heart failure and to genetically cardiomyopathic BIO TO.2 hamsters for 34 weeks orally. The parameters recorded were arrhythmic events and hemodynamic effects in dogs and mortality in hamsters. In dogs, istaroxime at 1, 3, and 4 μg/kg per min did not trigger arrhythmic events or magnify preexisting events. It increased left ventricular (LV) dP/dtmax (about 50% at 3 μg/kg per min) and LV - dP/dtmax (about 20% at 3 μg/kg per min) without changing heart rate, blood pressure, or double product. At 4 μg/kg per min, istaroxime increased dP/dtmax >100% but induced intense emesis in all animals. In cardiomyopathic hamsters, the dose of 30 mg/kg prolonged the survival rate to 32%. In conclusion, istaroxime seems to be a promising and safe new drug for improving cardiac performance in the failing heart.
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U2 - 10.1016/j.amjcard.2006.09.004
DO - 10.1016/j.amjcard.2006.09.004
M3 - Article
C2 - 17239702
AN - SCOPUS:33846188924
VL - 99
JO - American Journal of Cardiology
JF - American Journal of Cardiology
SN - 0002-9149
IS - 2 SUPPL.
ER -