Pecha Simon, Geelhoed Bastiaan, Kempe Romy, Berk Emanuel, Engel Andreas, Girdauskas Evaldas, Reichenspurner Hermann, Ravens Ursula, Kaumann Alberto, Eschenhagen Thomas, Schnabel Renate B, Christ Torsten
Institute of Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Department of Cardiovascular Surgery, University Heart and Vascular Center, Hamburg, Germany.
Acta Physiol (Oxf). 2021 Mar;231(3):e13564. doi: 10.1111/apha.13564. Epub 2020 Oct 29.
There is an increasing awareness of the impact of age and sex on cardiovascular diseases (CVDs). Differences in physiology are suspected. Beta-adrenoceptors (beta-ARs) are an important drug target in CVD and potential differences might have significant impact on the treatment of many patients. To investigate whether age and sex affects beta-AR function, we analysed a large data set on beta-AR-induced inotropy in human atrial trabeculae.
We performed multivariable analysis of individual atrial contractility data from trabeculae obtained during heart surgery of patients in sinus rhythm (535 trabeculae from 165 patients). Noradrenaline or adrenaline were used in the presence of the beta -selective antagonist (ICI 118 551, 50 nmol/L) or the beta -selective antagonist (CGP 20712A, 300 nmol/L) to stimulate beta -AR or beta -AR respectively. Agonist concentration required to achieve half-maximum inotropic effects (EC ) was taken as a measure of beta-AR sensitivity.
Impact of clinical variables was modelled using multivariable mixed model regression. As previously reported, chronic treatment with beta-blockers sensitized beta-AR. However, there was no significant interaction between basal force, maximum force and beta-AR sensitivity when age and sex were modelled continuously. In addition, there was no statistically significant effect of body mass index or diabetes on atrial contractility.
Our large, multivariable analysis shows that neither age nor sex affects beta-AR-mediated inotropy or catecholamine sensitivity in human atrial trabeculae. These findings may have important clinical implications because beta-ARs, as a common drug target in CVD and heart failure, do not behave differently in women and men across age decades.
人们越来越意识到年龄和性别对心血管疾病（CVD）的影响。怀疑存在生理差异。β-肾上腺素能受体（β-ARs）是心血管疾病中的一个重要药物靶点，潜在差异可能对许多患者的治疗产生重大影响。为了研究年龄和性别是否会影响β-AR功能，我们分析了一组关于人房小梁中β-AR诱导的心肌收缩力的大型数据集。
我们对窦性心律患者心脏手术期间获取的小梁的个体心房收缩力数据进行了多变量分析（来自165例患者的535个小梁）。在存在β-选择性拮抗剂（ICI 118 551，50 nmol/L）或β-选择性拮抗剂（CGP 20712A，300 nmol/L）的情况下，分别使用去甲肾上腺素或肾上腺素刺激β-AR或β-AR。将达到最大肌力效应一半所需的激动剂浓度（EC）作为β-AR敏感性的指标。
使用多变量混合模型回归对临床变量的影响进行建模。如先前报道，β受体阻滞剂的长期治疗使β-AR敏感。然而，当对年龄和性别进行连续建模时，基础力、最大力和β-AR敏感性之间没有显著相互作用。此外，体重指数或糖尿病对心房收缩力没有统计学上的显著影响。
我们的大型多变量分析表明，年龄和性别均不影响人房小梁中β-AR介导的心肌收缩力或儿茶酚胺敏感性。这些发现可能具有重要的临床意义，因为β-ARs作为心血管疾病和心力衰竭中的常见药物靶点，在不同年龄段的男性和女性中表现并无差异。
