A randomized trial comparing two different approaches of pacemaker selection.

AIMS: DDD-pacemakers are favoured in patients with sick-sinus-syndrome or AV-block. However, AAI-pacemakers for sick-sinus-syndrome or VDD-pacemakers for AV-block may provide similar benefit with lower costs. The aim is to show that a tailored approach (TA) with arrhythmia-specific pacemaker selection was equal to a standard approach (SA) regarding quality of life (QoL) at lower costs. METHODS AND RESULTS: The study was prospective and randomized with QoL as primary endpoint. Secondary endpoints were a combined endpoint of all-cause mortality, worsening heart failure or angina, atrial fibrillation (AF), stroke, these endpoints individually and costs. Of 198 patients (age 77 +/- 10 years, 43% female, ejection fraction 54 +/- 12%, follow-up 38 +/- 15 months), 94 were randomized to SA and 104 to TA. Thirty-two patients (34%) died in the SA group vs. 25 (24%) in the TA (P= ns). QoL showed no differences in all dimensions. The combined secondary endpoint was reached more frequently with SA (51%) compared to TA (37%, P = 0.045). There was no difference regarding all single secondary endpoints. Hardware costs were reduced by 15% (P < 0.0001). CONCLUSION: In long-term follow-up, a TA is equal to SA regarding the primary endpoint QoL and secondary endpoints as AF and mortality. Depending on the healthcare system, it may significantly reduce costs.     

Purine agonists prevent trophic changes caused by sympathetic denervation

Surgical denervation of the lateral saphenous vein of the dog causes marked extraneuronal changes, both of a morphological and functional type. In an attempt to investigate the factor(s) responsible for the trophic effects exerted by the sympathetic innervation on the dog saphenous vein we studied the effects of noradrenaline, adenosine, inosine and N-ethylcarboxamidoadenosine (NECA) on vascular tissue after sympathetic denervation. The saphenous vein was denervated using either surgical or chemical (6-hydroxydopamine, 6-OHDA) methods. Noradrenaline (0.1 microgram/kg per h), adenosine (10 micrograms/kg per h), inosine (10 micrograms/kg per h) or NECA (0.1 microgram/kg per h) were delivered continuously for 5 days through Alzet minipumps connected to the vein. 6-OHDA-induced denervation resulted in morphological changes similar to those described for surgical denervation. Smooth muscle cells and fibroblasts showed ultrastructural signs of increased synthetic activity and their size was significantly increased. In confirmation of earlier studies, constant i.v. infusions of noradrenaline did not prevent the morphological changes induced by denervation. Adenosine prevented the morphological changes induced by chemical or surgical denervation. Similarly to adenosine, infused NECA prevented the structural consequences of denervation. In contrast, inosine did not prevent the changes caused by surgical denervation. The results are compatible with an involvement of purines in the trophic effects of sympathetic innervation. Moreover, the effects of adenosine do not appear to be mediated by inosine.     

Pertussis toxin and N-ethylmaleimide inhibit histamine- but not calcium ionophore-induced endothelium-dependent relaxation

Summary Endothelium-dependent relaxation of the guinea pig pulmonary artery induced by histamine was inhibited by preincubation of the tissue with 10 M N-ethylmaleimide (NEM) for 10 min, whereas the endothelium-dependent relaxation induced by the calcium ionophore A 23187 was not affected by NEM. Pretreatment of the preparations with 0.2–1 g/ml pertussis toxin for 120 min inhibited concentration-dependently the histamine-induced relaxation. In contrast, endothelium-dependent relaxation in response to the calcium ionophore A 23187 was not affected by pertussis toxin. Since NEM and pertussis toxin are thought to interfere with membrane located GTP binding proteins, it is suggested that such a coupling protein is involved in the signal transduction of the histamine receptor leading to endothelium-dependent relaxation.A preliminary report of these results was presented at the autumn Meeting of the Deutsche Pharmakologische Gesellschaft, 1986 Send offprint requests to G. Weinheimer at the above address