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

Toborinone ((+/-)-6-[3-(3,4-dimethoxybenzylamino)-2-hydroxypropoxy]-2(1H)-qui nolinone, 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 extracorporeal circulation (ECC) in cardiac surgery was investigated. The study was conducted in 12 patients with valvular heart disease showing a cardiac index (CI) of below 2.8 l/min/m2 and/or pulmonary capillary wedge pressure (PCWP) or pulmonary arterial diastolic pressure (PAD) of above 8 mmHg immediately after extracorporeal circulation. In group A (n = 6), toborinone was infused at a rate of 40 micrograms/kg/min for the first 5 min and then at 10 micrograms/kg/min for 85 min. In group B (n = 6), the drug was infused at a rate of 10 micrograms/kg/min for the entire 90 min. CI, mean systemic arterial pressure (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. The infusion volume required to maintain a constant PCWP was also estimated. In group A, CI increased rapidly and significantly from the baseline of 2.48 +/- 0.23 l/min/m2 to 3.57 +/- 1.07 l/min/m2 at 5 min after the start of infusion, and at that time mSAP was slightly decreased. In group B, CI increased gradually from the baseline of 2.53 +/- 0.18 l/min/m2 to 3.08 +/- 0.34 l/min/m2 at 15 min after the start of infusion, but almost no change was seen in mSAP. During the first 30 min, group A required a significantly larger infusion volume (983 +/- 395 ml) than group B (475 +/- 184 ml). From 30 to 90 min after the start of infusion, CI remained increased to similar 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 heart failure occurring immediately after ECC in cardiac surgery. Initial loading at a rate of 40 micrograms/kg/min rapidly increased CI but was accompanied by mild hypotension. Constant infusion at 10 micrograms/kg/min brought about a more gradual effect that was similar to that of loading at 40 micrograms/kg/min, but without inducing hypotension. Thus, infusion at 10 micrograms/kg/min is considered preferable in order to avoid a larger-than-necessary infusion volume.

[Comparison of cerebral oxygen metabolism during normothermic versus moderate hypothermic cardiopulmonary bypass].

We compared the effects of normothermic (NCPB, N = 5) and moderate hypothermic (HCPB, (N = 5) cardiopulmonary bypass on cerebral oxygen metabolism in patients undergoing coronary artery bypass grafting. For monitoring of cerebral oxygenation, we used jugular venous oxyhemoglobin saturation (SjVO2) and near infrared spectroscopy (NIR). In NCPB group, although SjVO2 decreased temporally at the start of cardiopulmonary bypass, it became stabilized above 50% during the rest of cardiopulmonary bypass. In HCPB group, on the contrary, oxyhemoglobin measured by NIR showed maximum decrease during rewarming under cardiopulmonary bypass. Furthermore, SjVO2 decreased under 50% at the end of cardiopulmonary bypass (3/5 cases). We consider that NCPB is a useful technique for preventing cerebral hypoxia, if the decrease of SjVO2 during the early period of cardiopulmonary bypass is avoidable. Lastly, we also advocate that both SjVO2 and NIR are useful monitoring systems for continuous evaluation of cerebral oxygen metabolism during cardiopulmonary bypass.

[Usefulness of monitoring with near infrared spectroscopy during retrograde cerebral perfusion].

Recently retrograde cerebral perfusion (RCP), a newly developed technique for cerebral protection during surgical replacement for thoracic aortic aneurysm, has been used in many institutes. However, there is no established monitoring methods for cerebral oxygenation during this procedure. In the present study, we examined if near infrared spectroscopy (NIR) is useful for monitoring cerebral oxygenation during RCP. We studied 7 patients undergoing operations for aneurysms of the ascending aorta and transverse arch in the supine position (Group A) and another seven patients undergoing operations for aneurysms of the transverse arch and descending aorta in the lateral decubitus position (Group D) in this study and monitored cerebral oxygenation with NIR. NIR showed a slow but continuous decrease in oxygenated hemoglobin and an increase in deoxygenated hemoglobin during RCP, while these changes disappeared following the termination of RCP. The degree of these changes in Group D was significantly greater than that in Group A. In comparison, we observed rapid reduction of oxygenated hemoglobin during the period of circulatory arrest and low perfusion pressure with NIR, suggesting the usefulness of RCP for cerebral oxygenation. NIR may be a useful method of monitoring cerebral oxygenation during RCP.

Effect of Fluosol-DA on the blood coagulation/fibrinolytic system and the renin-angiotensin system in man.

Either F-DA, Ringer's lactate or HES was given to three groups of six patients each who were undergoing elective gynecologic surgery, and their effects on the blood coagulation/fibrinolytic systems, and the renin-angiotensin systems were evaluated. Platelet counts were found to increase markedly using the Coulter Counter method, but no change was observed when the Rees-Ecker method was used. Platelet aggregation was inhibited and AT-III concentrations were decreased by administration of F-DA. There were no significant changes in PT or a-PTT as a result of F-DA administration. Similarly, there were no significant changes in the concentrations of fbg, FDP, a2-PI, P-FN and renin, angiotensin I, II and angiotensin converting enzyme following F-DA administration. Based upon these findings, it is suggested that a clinical dosage of 20 to 30 ml/kg of F-DA can be safely administered to patients with normal platelet and RES function.