Study on the effectiveness of toborinone (OPG-18790) in the treatment of heart failure in patients following cardiac surgery

Toborinone ((+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-q uinolinone, CAS 128667-95-8, OPC-18790), a novel cardiotonic agent with an inhibitory action on phosphodiesterase, is known to have a potent positive inotropic action with no positive chronotropic effect. The effectiveness of this drug in the treatment of heart failure occurring immediately after ex tracorporeal circulation (ECC) in cardiac surgery was investigated. The stu dy was conducted in 12 patients with valvular heart disease showing a cardi ac index (CI) of below 2.81/min/m(2) and/or pulmonary capillary wedge press ure (PCWP) or pulmonary arterial diastolic pressure (PAD) of above 8 mmHg i mmediately after extracorporeal circulation. In group A (n = 6), toborinone was infused at a rate of 40 mu g/kg/min for the first 5 min and then at 10 mu g/kg/min for 85 min. In group B (n = 6), the drug was infused at a rate of 10 mu g/kg/min for the entire 90 min. CI, mean systemic arterial pressu re (mSAP), mean pulmonary artery pressure (mPAP), CVP, PCWP, and heart rate were measured at 5, 15, 30, 60, and 90 min after the start of infusion. Th e infusion volume required to maintain a constant PCWP was also estimated. In group A, CI increased rapidly and significantly from the baseline of 2.4 8 +/- 0.23 l/min/m(2) to 3.57 +/- 1.07 l/min/m(2) at 5 min after the start of infusion, and at that time mSAP was slightly decreased. In group B, CI i ncreased gradually from the baseline of 2.53 +/- 0.18 l/min/m(2) to 3.08 +/ - 0.34 l/min/m(2) at 15 min after the start of infusion, but almost no chan ge was seen in mSAP. During the first 30 min,,group A required a significan tly larger infusion volume (983 +/- 395 mi) than group B (475 +/- 184 mi). From 30 to 90 min after the start of infusion, CI remained increased to sim ilar levels in both groups and mSAP levels were also similar. There were no significant differences between the two groups in any other parameter. Continuous infusion of toborinone appears to be effective for treating hear t failure occurring immediately after ECC in cardiac surgery. Initial loadi ng at a rate of 30 mu g/kg/min rapidly increased CI but was accompanied by mild hypotension. Constant infusion at 10 mu g/kg/min brought about a more gradual effect that was similar to that of loading at 40 mu g/kg/min, but w ithout inducing hypotension. Thus, infusion at 10 mu g/kg/min is considered preferable in order to avoid a larger-than-necessary infusion volume.