Interactions of a new beta-blocker,celiprolol, with the calcium antagonists,diltiazem and nifedipine,on atrioventricular conduction

Summary The influence of a new beta-blocker, celiprolol, on the direct dromotropic effects of the Ca antagonists, diltiazem and nifedipine, on atrioventricular (AV) conduction was estimated in the canine isolated, blood-perfused AV node preparation. Diltiazem (1–10 µg) and nifedipine (0.3–3 µg) injected i.a. into the AV node artery dose dependently prolonged the atrio-His (AH) interval (5–39 msec and 7–51 msec) in the AV mode preparation. When celiprolol (1 and 10 mg/kg) was given i.v. in the support dog, the AH interval in the AV node preparation was transiently shortened and then maintained constant as a control. These doses of i.v. celiprolol completely abolished the isoproterenol-induced decrease in the AH interval (28 msec at 0.03 µg, i.a.) and AV nodal tachycardia. In the presence of celiprolol, the same doses of i.a. diltiazem and nifedipine increased the AH interval by the same amounts (6–43 msec and 8–53 msec) as the control. The incidence of second degree AV conduction block produced by diltiazem (2 in 5 AV node preparations at 10 µg) and nifedipine (2 in 6 preparations at 3 µg) was not changed by celiprolol. In the second experiments, diltiazem (30–300 µg/kg) and nifedipine (3–30 µg/kg), given i.v. in an open-chest in situ vagotomized dog, dose dependently increased AV conduction time (AVCT; 2–30 msec and 1–12 msec). Celiprolol 1 and 10 mg/kg i.v., which suppressed the isoproterenol-induced decrease in AVCT (32 msec at 0.3 µ/kg i.v.) and AV nodal tachycardia (4 in 6 in situ hearts), potentiated the prolongation of AVCT by the same doses of diltiazem (11–50 msec) and nifedipine (3–40 msec). The incidence of second degree AV conduction block produced by i.v., diltiazem (1 in 5 in situ hearts at 300 µg/kg) and nifedipine (0 in 6 in situ hearts at 30 µg/kg) was aggravated (4 in 5 and 3 in 6 in situ hearts) after i.v. celiprolol. These results indicate that although celiprolol does not affect thedirect negative dromotropic effects of the Ca antagonists, AV block could easily be produced when celiprolol eliminates tonic adrenergic influences in vivo.     

Neonatal lupus syndromes

Children born from mothers positive for autoantibodies against SSA/Ro and/or anti‐SSB/La ribonucleoproteins may develop heart conduction tissue damage resulting in atrioventricular block and/or transient skin rash, liver enzyme abnormalities and anaemia/thrombocytopenia. Additional transient electrocardiographic abnormalities (sinus bradycardia, QT interval prolongation) have been reported. Such clinical and laboratory manifestations are included in the so‐called neonatal lupus syndromes, independently whether the mother is suffering from a systemic autoimmune disease or is totally asymptomatic. The prevalence of the congenital heart block is around 2%, of neonatal rash around 20%, while laboratory abnormalities in asymptomatic babies can be detected in up to 40% of cases. The risk of recurrence of complete heart block is almost 10 times higher in the following pregnancies. Most of the mothers are asymptomatic at delivery and are identified only by the birth of an affected child. Their long‐term outcome is generally more reassuring than previously assumed and arthralgias and xerophtalmia are the most common symptoms. A standard therapy for heart blocks detected in uterus is still a matter of investigation, although fluorinated corticosteroids have been reported to be effective on myocarditic signs when present. Serial echocardiograms and obstetric sonograms, performed at least every two weeks, starting from the 16 weeks gestation, are recommended in anti‐Ro/SSA positive pregnant women: the goal is to detect early fetal abnormalities, that might precede complete atrioventricular block and that might be a target of preventive therapy. Transplacental passage of maternal anti‐SSA/Ro ‐SSB/La IgG is thought to be pivotal in inducing tissue damage. However, the discordant appearance of the syndrome in twins does suggest a role also for fetal or environmental factors.