Abstract
In vitro, the Arg389Gly-β1-adrenoceptor (AR) polymorphism exhibits decreased receptor signaling. In vivo, dobutamine infusion evoked smaller heart rate and/or contractility increases in subjects carrying Gly389Gly-β1AR vs subjects carrying Arg389Arg-β1AR. The aim of this study was to find out whether the Arg389Gly-β1AR polymorphism might also determine demand of catecholamine-induced inotropic support in patients with low cardiac index (CI) after coronary artery bypass grafting (CABG) surgery with cardiopulmonary bypass (CPB). For this purpose, we assessed in 82 patients, who were preoperatively chronically treated with metoprolol, after CABG surgery with CPB, the dose and duration of adrenaline-induced inotropic support in relation to the Arg389Gly-β1AR genotype. Patients homozygous for the Arg389-β1AR variant (n = 45) required, in comparison to patients homozygous for the Gly389-β1AR variant (n = 9), lower adrenaline doses (53 ± 24 vs 164 ± 39 ng/kg body weight/min, p < 0.05) to reach a stable and comparable hemodynamic status and a CI ≥ 3.0 l/min/m2. Moreover, the time necessary for inotropic support tended to be shorter in patients homozygous for the Arg389-β1AR than in patients homozygous for the Gly389-β1AR (10.5 ± 6 vs 20.5 ± 12 h). Values for patients heterozygous for the Arg389Gly-β1AR (n = 28) were in between. We conclude that the Arg389Gly-β1AR polymorphism appears to be a determinant of cardiac responses to catecholamine stimulation. Thus, by assessment of the Arg389Gly-β1AR polymorphism, it might be possible to predict demand of and therapeutic responses to βAR agonist treatment.
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Acknowledgement
This work was supported by a grant (BR 526/8-3 to O.-E. B.) of the Deutsche Forschungsgemeinschaft Bonn, Germany.
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Leineweber, K., Bogedain, P., Wolf, C. et al. In patients chronically treated with metoprolol, the demand of inotropic catecholamine support after coronary artery bypass grafting is determined by the Arg389Gly-β1-adrenoceptor polymorphism. Naunyn-Schmied Arch Pharmacol 375, 303–309 (2007). https://doi.org/10.1007/s00210-007-0166-6
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DOI: https://doi.org/10.1007/s00210-007-0166-6