Acute hemodynamic effects of a new inotropic agent,OPC-8212, on severe congestive heart failure

Summary The hemodynamic and clinical effects of OPC-8212, a newly synthesized, orally effective inotropic agent, were assessed for the first time in ten patients with severe congestive heart failure by means of right heart catheterization with a Swan-Ganz catheter. Cardiac output was determined by the thermodilution technique. Patients received a single oral dose of 6 mg/kg. To determine the magnitude and time-course of the effects of OPC-8212, measurements were made during an observation period before and 2, 4, 8, and 12 h after administration. Blood was also taken at these times for measurement of the concentration of plasma OPC-8212. No large meals were allowed during the first 4 h. After the single oral dose of OPC-8212, plasma concentrations increased rapidly, reaching an effective level after 8 h and peaking at 12 h. Hemodynamic performance improved as the mean OPC-8212 plasma level increased, with the maximum effect being observed between 8 and 12 h after acute administration of the drug. At 8 h, the cardiac index was increased from the baseline value of 2.4±0.2 (SEM) to 2.8±0.3 l/min/m² (P<0.01). The stroke work index rose from 26.2±5.1 to 31.7±60 g · m/m². The excessive pulmonary artery diastolic pressure fell from 22±2 to 17±3 mmHg at 8 h (P<0.001) and to 16±2 mmHg (P<0.001) at 12 h. The incidence of ventricular premature beats was not increased and no other side effects were observed. These changes were not associated with significant changes in heart rate or systolic blood pressure. Thus, this drug appears to be very promising for the long-term treatment of congestive heart failure.