Artikel
Bucindolol, a beta-adrenoceptor blocker with intrinsic sympathomimetic activity?
: ein Beta-Adrenozeptorblocker mit intrinsischer sympathomimetischer Aktivität ?
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Autoren
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H. Bruck
- Universitätsklinikum Essen (Essen, D)
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C. Giessler
- Universitätsklinikum Essen (Essen, D)
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T. Temme
- Universitätsklinikum Essen (Essen, D)
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O. Brodde
- Universitätsklinikum Essen (Essen, D)
| Veröffentlicht: | 10. August 2005 |
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Gliederung
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Background: Beta-adrenoceptor (AR) blockers are now commonly used in therapy of chronic heart failure. Various studies have shown beneficial effects (reduced mortality) of bisoprolol, metoprolol and carvedilol, while xamoterol, a beta-AR blocker with intrinsic sympathomimetic activity (ISA), exerted adverse effects on mortality. Obviously ISA exerts adverse effects in heart failure treatment. We, therefore, studied whether the beta-AR blockers bisoprolol, metoprolol, carvedilol and bucindolol (all used in heart failure trials) may exert ISA.
Methods: For this purpose we determined, on spontaneously beating right atria of rats pretreated with reserpine (10 mg/kg i.p. 24 h before study), the chronotropic effects of the beta-AR blockers in comparison to isoprenaline (ISO).
Results: In reserpine treated right atria tyramine (up to 10-4 M) failed to exert positive chronotropic effects while isoprenaline (10-10 - 10-6 M) increased heart rate (HR) by 180 ± 23 bpm (n=7, 100%). Celiprolol (n=6) and pindolol (n=5), two well known beta-AR blockers with ISA, increased HR by 38±7 respectively 24±6 bpm (38 and 24%, respectively, of the ISO-effect), while metoprolol, bisoprolol and carvedilol (n=5 each) did not show positive chronotropic activity. Bucindolol (10-10 - 10-6 M), however, increased HR concentration-dependently; maximum increase was 29 ± 6 bpm (n=5, 17% of the ISO-effect). On the other hand, all beta-AR blockers significantly attenuated ISO-induced HR-increases.
Conclusion: These results confirm that bisoprolol, metoprolol and carvedilol are devoid of ISA; bucindolol, however, exerts a certain degree of ISA which might explain why, in the BEST-trial, bucindolol failed to show benefical effects on mortality in patients with chronic heart failure.
