Methods: Studies were performed in 7 dogs with coronary microembolizations-induced HF. After baseline measurements, 0.9% NaCl (vehicle) was administered as a continuous i.v. infusion for 30 min. This was followed by infusions of 3 escalating doses of APD418 (0.696, 1.407 and 2.814 mg/kg) with each dose maintained for 30 min. Heart rate (HR), mean aortic pressure (mAoP), LV end-diastolic (EDV) and end-systolic (ESV) volumes, EF, stroke volume (SV) cardiac output (CO), LV end-diastolic pressure (EDP) and systemic vascular resistance (SVR) as well as the diastolic function measures Ei/Ai and mitral inflow velocity deceleration time (DCT) were measured at end of each 30 min period.
Results: Infusion of APD418 had no effects on HR, mAoP, or EDV but significantly decreased ESV, LVEDP and SVR and significantly increased EF, SV, CO Ei/Ai and DCT in a dose-dependent manner (Table).
Conclusions: Acute i.v. infusions of APD418 in HF dogs elicit positive inotropic and lusitropic effects along with modest preload and afterload reductions. The findings support the development of APD418 for the in-hospital treatment of patients with exacerbation of chronic HF.