Frequency-dependent electrophysiological effects of flecainide, nifekalant and d,l-sotalol on the human atrium.

To compare the effects of class Ic and III antiarrhythmic agents on the termination and prevention of atrial fibrillation, the present study investigated the use-dependent electrophysiological effects of flecainide, nifekalant and d,l-sotalol on the human atrium. Flecainide significantly prolonged effective refractory period (ERP), intra-atrial conduction time (IACT) and monophasic action potential duration (MAPD), and its effects on ERP and IACT were use-dependent. Nifekalalant significantly prolonged ERP and MAPD, and these effects were reverse use-dependent; however, there was no significant change in IACT. d,l-Sotalol significantly prolonged MAPD and the effect was reverse use-dependent. It significantly prolonged ERP, but the effect was not reverse use-dependent. d,l-Sotalol increased IACT in a use-dependent manner. Thus, for atrial fibrillation, class Ic antiarrhythmic agents might be more effective in termination and class III antiarrhythmic agents might be more effective in prevention.

Thrombolysis of canine femoral artery thrombus by a novel modified tissue-type plasminogen activator (E6010).

The thrombolytic activity of a novel modified tissue-type plasminogen activator (t-PA) (E6010) was examined in a canine model with copper coil-induced femoral artery thrombus. This model, in which thrombolytic activity can be easily and directly quantified by determining changes in thrombus weight, should be useful for comparing the activities of various thrombolytic agents. Using this model, the present study showed that the thrombolytic activity of bolus intravenous injection of E6010 was identical to that of continuous intravenous infusion of recombinant t-PA at the same dose. This thrombolytic activity can be explained by changes in blood concentrations of the administered thrombolytic agents. On the other hand, administration of the thrombolytic agents dose-dependently caused significant changes in the levels of hemostatic and fibrinolytic factors. These changes were not so marked with administration of E6010, and therefore we concluded that E6010 is unlikely to cause bleeding complications after administration.

[The significance of early coronary reperfusion in patients with acute myocardial infarction assessed by regional wall motion].

Left ventricular ejection fraction, regional wall motion, hospital mortality rate, and reocclusion rate of the infarct-related coronary artery after thrombolytic therapy were examined in 164 consecutive patients who were admitted within 12 hours of the onsets of their symptoms of acute myocardial infarction. The patients were divided into three groups based on the findings of initial coronary angiography before and after administration of urokinase: (1) stenosed (the infarct-related coronary blood flow was visualized at initial angiography) (n = 41); (2) successfully thrombolysed (n = 82); and (3) unsuccessful (n = 41). The patients in each group were also subdivided into three subgroups based on the recanalized time (hours): within three, three to six hours and six hours or longer. The hospital mortality rates were 4.9% (two of the 41 patients) in the stenosed; 8.5% (seven of the 82 patients) in the thrombolysed; 29.3% (12 of the 41 patients) in the unsuccessful group, and 12.8% (21 of the 164 patients) overall, respectively. There were significant differences among these three groups. The incidence of pump failure as a cause of death in the acute stage was significantly low in the stenosed (two of the 41 patients) and in the thrombolysed (3 of the 82 patients) groups compared to the unsuccessful group (eight of the 41 patients). The rates of rethrombosis one month after thrombolytic treatment were 3% in the stenosed and 4% in the thrombolysed groups. On the contrary, visualization of coronary blood flow at the chronic stage (approximately one month later) was confirmed in 19% of the patients in the unsuccessful group. Left ventricular ejection fraction one month after thrombolytic therapy in the subgroup with the recanalized coronary arteries within three hours was significantly higher than that of the unsuccessful group, but, after three hours of procedure, no significant difference of left ventricular ejection fraction was present among three groups. Regional wall motion in patients with the recanalized coronary artery within 12 hours was better than that of the unsuccessful group. The area of improved wall motion was wide in patients with early recanalization in the stenosed and thrombolysed groups. Thus, early recanalization within three hours is mandatory for reducing mortality and for improving ejection fraction and wall motion.