Hemodynamic Effects of a New Inotropic Compound, PST-2744, in Dogs With Chronic Ischemic Heart Failure

Inotropic agents for acute decompensated heart failure are associated with a lack of efficacy or increased mortality. New compounds are needed to support patients with acute exacerbations of heart failure. This study examined the hemodynamic effects of a new inotropic agent (PST-2744) in dogs with chronic ischemic heart fail- ure. Eight mongrel dogs at low risk for postmyocardial infarction (MI) sudden death entered the protocol. Dogs were studied after isch- emic left ventricular dysfunction was induced by repeated injections of latex microspheres into the circumflex artery until the ejection frac- tion reached 35%. Hemodynamic parameters were measured at base- line and peak drug effect (PST-2744 5 µg·kg �1 ·min �1 ). In 5 animals, PST-2744 effects were compared with dobutamine. Heart rates, PR intervals and QT intervals were unchanged following PST-2744 ad- ministration. PST-2744 increased contractility (+dP/dt) by 56% from 1881 ± 282 mm Hg/s to 2939 ± 734 mm Hg/s (P < 0.01). The inotropic effect of PST-2744 was equal to that produced by 5-µg·kg �1 ·min �1 dobutamine (56% increase in +dP/dt), but peak heart rates were sig- nificantly higher with dobutamine (129 ± 24 bpm PST-2744 versus 160 ± 6 bpm 5-µg·kg �1 ·min �1 dobutamine, P < 0.002). No arrhyth- mias or conduction delays were seen with either compound. PST- 2744 is an effective inotropic agent without positive chronotropic ef- fect in subjects with stable moderate left ventricular dysfunction.