Geng Zhao-Hua, Liu Chun-Yan, Peng You-Hua, Li Long-Gui, Zhao Xiao-Hui, Cui Bin, Yu Shi-Yong
Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Nan Fang Yi Ke Da Xue Xue Bao. 2009 Jul;29(7):1461-4.
To study the effects of carvedilol combined with perindopril on Ca(2+) pump activity and the density of Ca(2+)-release channel ryanodine receptor (RyR2) in the myocardial sarcoplasmic reticulum (SR) in rats with chronic heart failure caused by myocardial infarction.
Rat models of chronic heart failure established by left coronary artery ligation were divided into different groups and treated with carvedilol (6 mg.kg(-1).d(-1)), perindopril (4 mg.kg(-1).d(-1)), terazosin (2 mg.kg(-1).d(-1)), or the combination of carvedilol (6 mg.kg(-1).d(-1)) and perindopril (4 mg.kg(-1).d(-1)) for 9 weeks. Another 12 rats with sham operation served as the sham-operated group. The hemodynamic parameters, activity of SR Ca(2+) pump, and RyR2 density were determined.
Compared with shame-operated group, the rats with chronic heart failure showed significantly increased left ventricular end-diastolic pressure (LVEDP) (P<0.01) and decreased +dP/dtmax, -dp/dtmax, activity of SR Ca(2+) pump and density of RyR2 (P<0.01). Both monotherapies with carvedilol and perindopril attenuated the increment of LVEDP, and significantly increased +dp/dtmax, -dp/dtmax, activity of SR Ca(2+) pump and density of RyR2 (P<0.01). Combined treatment even further enhanced the therapeutic effects, whereas terazosin produced no obvious effect. The activity of SR Ca(2+) pump was strongly correlated to +dp/dtmax and -dp/dtmax (r=0.596 and 0.684, respectively, P<0.01).
Prolonged treatment with beta-blocker carvedilol in combination with ACE inhibitor perindopril may improve the hemodynamic parameters, enhance Ca(2+) pump activity and increase the density of RyR2 of myocardial SR more effectively than either monotherapy in preventing and treating chronic heart failure following myocardial infarction.
研究卡维地洛联合培哚普利对心肌梗死后慢性心力衰竭大鼠心肌肌浆网（SR）中Ca(2+)泵活性及Ca(2+)释放通道兰尼碱受体（RyR2）密度的影响。
将通过左冠状动脉结扎建立的慢性心力衰竭大鼠模型分为不同组，分别给予卡维地洛（6 mg·kg(-1)·d(-1)）、培哚普利（4 mg·kg(-1)·d(-1)）、特拉唑嗪（2 mg·kg(-1)·d(-1)）或卡维地洛（6 mg·kg(-1)·d(-1)）与培哚普利（4 mg·kg(-1)·d(-1)）联合治疗9周。另外12只假手术大鼠作为假手术组。测定血流动力学参数、SR Ca(2+)泵活性及RyR2密度。
与假手术组相比，慢性心力衰竭大鼠左心室舒张末期压力（LVEDP）显著升高（P<0.01），+dP/dtmax、-dp/dtmax、SR Ca(2+)泵活性及RyR2密度降低（P<0.01）。卡维地洛和培哚普利单药治疗均减轻了LVEDP的升高，并显著提高了+dP/dtmax、-dp/dtmax、SR Ca(2+)泵活性及RyR2密度（P<0.01）。联合治疗进一步增强了治疗效果，而特拉唑嗪未产生明显效果。SR Ca(2+)泵活性与+dP/dtmax和-dp/dtmax密切相关（r分别为0.596和0.684，P<0.01）。
在预防和治疗心肌梗死后慢性心力衰竭方面，β受体阻滞剂卡维地洛与ACE抑制剂培哚普利联合长期治疗可能比单药治疗更有效地改善血流动力学参数，增强Ca(2+)泵活性并增加心肌SR的RyR2密度。
