Laboratory of Cardiovascular Sciences, National Institute on Aging, Intramural Research Program, Gerontology Research Center, NIH, 5600 Nathan Shock Drive, Baltimore, MD, 21224-6825, USA.
Cardiovasc Drugs Ther. 2012 Apr;26(2):101-8. doi: 10.1007/s10557-011-6366-9.
A salutary effect of β(2) adrenergic receptor (AR) agonist, fenoterol has been demonstrated in a rat model of post-myocardial infarction (MI) dilated cardiomyopathy (DCM). Recent reports on single cardiomyocyte experiments suggested that out of two enantiomers, RR and SS, that constitute a racemic mixture of fenoterol, only RR-enantiomer is an active component that might be a promising new drug for treatment of chronic heart failure. The objective of this study was to compare the efficacy of the RR enantiomer of fenoterol with efficacy of racemic fenoterol, and SS, an inactive enantiomer, in whole animal experimental models of DCM.
Two weeks after induction of MI by permanent ligation of the anterior descending coronary artery early cardiac remodeling and MI size were assessed via echocardiography and rats were divided into treatment groups. Treatment (placebo, racemic fenoterol, RR- or SS-enantiomers of fenoterol) continued for 6 months while progression of DCM was followed by serial echocardiography.
Compared with untreated rats, rats treated with racemic fenoterol demonstrated previously described attenuation of LV remodeling, functional decline and the arrest of the MI expansion during the first 2 months of treatment. On the contrary, the treatment with either RR-, or with SS-enantiomers of fenoterol was completely ineffective.
The conclusion drawn on the basis of previous experiments with single cardiomyocytes that RR-enantiomer of fenoterol represents an active component of racemic fenoterol and can be further investigated as a new drug for treatment of chronic heart failure was not confirmed in the whole animal model of DCM.
β（2）肾上腺素能受体（AR）激动剂福莫特罗在心肌梗死后扩张型心肌病（DCM）大鼠模型中显示出有益作用。最近关于单个心肌细胞实验的报告表明，在构成福莫特罗外消旋混合物的两个对映异构体 RR 和 SS 中，只有 RR-对映异构体是一种活性成分，可能是治疗慢性心力衰竭的一种有前途的新药。本研究的目的是比较 RR 对映异构体福莫特罗与外消旋福莫特罗和 SS（一种无活性对映异构体）在 DCM 动物实验模型中的疗效。
在前降支冠状动脉永久性结扎诱导 MI 后 2 周，通过超声心动图评估早期心脏重构和 MI 大小，并将大鼠分为治疗组。治疗（安慰剂、外消旋福莫特罗、RR-或 SS-对映异构体福莫特罗）持续 6 个月，同时通过连续超声心动图监测 DCM 的进展。
与未治疗的大鼠相比，用外消旋福莫特罗治疗的大鼠在前 2 个月的治疗期间，LV 重构、功能下降和 MI 扩张的停止得到了先前描述的衰减。相反，RR-或 SS-对映异构体福莫特罗的治疗完全无效。
基于以前的单个心肌细胞实验得出的结论，即 RR-对映异构体福莫特罗是外消旋福莫特罗的活性成分，并可进一步作为治疗慢性心力衰竭的新药进行研究，在 DCM 动物模型中并未得到证实。
