Yoshifumi Tanahashi

Effect of the autonomic blockade on the automaticity of the A-V junctional pacemaker in awake dogs**

The effect of the autonomic blockade on the automaticity of the A-V junctional pacemaker was evaluated in 15 awake dogs with experimentally induced A-V junctional rhythm. The duration of asystole after overdrive (D.A.O.) in these dogs was prolonged significantly in accordance with increase in the drive rate, and the mean +/- SD of the D.A.O. reached 4.7 +/- 1.1 seconds (N = 15) after overdrive at 2.5 times the spontaneous heart rate. After administration of atropine (0.4 mg/kg; i.v.) to eight dogs, the mean +/- SD of the D.A.O. at the same rate decreased from 4.5 +/- 0.9 to 3.4 +/- 1.2 seconds. After administration of practolol (0.5 mg/kg; i.v.) to the seven other dogs, the mean +/- SD of the D.A.O. at the same rate increased remarkably from 4.9 +/- 1.3 to 9.4 +/- 3.0 seconds. Intravenous injection of practolol (0.5 mg/kg) had no effect upon the D.A.O. in the five dogs with sinus rhythm. Thus, it is suggested that (1) the sympathetic nerve might play a more important role in regulating the automaticity of the A-V junctional pacemaker than the vagus and (2) it physiologically might take over 5.0 seconds for the A-V junctional pacemaker to initiate an escape beat during longstanding sinus arrest, if a marked dysfunction of the A-V junctional pacemaker occurs due to a decrease in tension of the sympathetic nerve.

Overdrive suppression in diagnosis of sick sinus syndrome.

A criterion to determine the indication for pacemaker implantation in the sick sinus syndrome by overdrive suppression is proposed. Overdrive suppression was performed in 10 patients with the sick sinus syndrome (SSS) and another 10 patients with normal sinus rhythm (NSR) who served as controls. In the SSS group, 9 patients had complained of such severe symptoms as Adams-Stokes attack and/or congestive failure and were referred to our laboratory for pacemaker implantation. One other patient, an apparently robust young man (20 years old) referred for detailed cardiac examination, had no remarkable symptoms except for arrhythmias, but was found dead two months later. Atrial pacing for overdrive suppression was carried out at first at various rates ranging from 60 to 180 beats/min for 15 sec, and then at a rate of 100 beats/min for various durations ranging from 5 to 180 sec. After cessation of the atrial pacing, asystolic pauses were measured and the maximum (maximum pause) among the pauses obtained was used as a parameter indicating depression of cardiac automaticity. The maximum pause in the SSS group ranged from 5.6 to 9.0 sec (mean +/- SD = 7.0 +/- 1.2), WHILE THOSE IN THE NSR group ranged from 0.7 to 1.5 sec (mean +/- SD = 1.2 +/- 0.14). Therefore, the maximum pause was considered not only to reflect the severity of the symptoms necessitating pacemaker implantation in the 9 patients of the SSS group but to have warned us of sudder death in another patient. We concluded that overdrive suppression is useful as a supplementary challenge to determine indications for pacemaker implantation for the sick sinus syndrome, and that prolongation of the maximum pause beyond 5.0 sec is the critical level for pacemaker implantation.

Long-term effects of niceritrol on serum lipoprotein(a) and lipids in patients with high levels of lipoprotein(a)

The long-term effects of niceritrol on lipoprotein(a) (Lp[a]), lipids, apolipoproteins, and fibrinogen and fibrinolytic factors were evaluated in 20 outpatients who had serum Lp(a) levels higher than 20 mg/dL. The mean ( +/- SE) levels of Lp(a) decreased from 33.6 +/- 2.3 mg/dL to 23.5 +/- 3.5 mg/dL after 12 months of niceritrol treatment (P < 0.01). Serum levels of triglycerides and apolipoprotein E decreased significantly and high-density lipoprotein cholesterol (HDL-C) increased significantly after 12 months (P < 0.05). There were no significant changes overall in fibrinogen and fibrinolytic factors, although fibrinogen concentrations showed a tendency to decrease with treatment. PAI-1 levels decreased significantly (P < 0.05) after 6 months of niceritrol treatment. A significant correlation of percent reduction between Lp(a) and apolipoprotein B levels (P < 0.01) was observed, suggesting that the Lp(a)-lowering effects of niceritrol may be due to niceritrol inhibition of apolipoprotein B synthesis, the major apolipoprotein of Lp(a). The ability of niceritrol to decrease Lp(a) levels and increase HDL-C levels, together with its tendency to lower fibrinogen levels, may help prevent coronary events in patients with high levels of Lp(a).