istaroxime is a positive inotropic agent that mediates its action through inhibition of sodium/potassium adenosine triphosphatase (na+/k+ atpase). istaroxime is an investigational drug originally patented and developed by the italian pharmaceutical company sigma-tau. istaroxime is now under development for treatment of acute decompensated heart failure by cvie therapeutics.
intravenous infusion of 0.2 mg/kg/min pst2744 in anesthetized guinea pigs exerted an immediate and long-lasting inotropic effect (ed(80) of 1.89 +/- 0.37 mg/kg) without causing lethal arrhythmias up to a cumulative dose of 18 mg/kg [1]. istaroxime intravenous infusion (0.11 mg/kg per min) significantly increased both indices of contraction and relaxation (fractional shortening, +18+/-3.7%; aortic flow rate, +19+/-2.9%; peak myocardial systolic velocity, +36+/-7%; circumferential fiber shortening, +24+/-4.1%; peak atrial flow velocity, +69+/-8.6%; isovolumic relaxation time, +19+/-6.9%; and peak myocardial early diastolic velocity, +42+/-12%) [3]. in 5 animals, pst-2744 effects were compared with dobutamine. heart rates, pr intervals and qt intervals were unchanged following pst-2744 administration. pst-2744 increased contractility (+dp/dt) by 56% from 1881 +/- 282 mm hg/s to 2939 +/- 734 mm hg/s (p < 0.01) [4].
