CAJ | 학술논문

目的探讨β受体阻滞剂卡维地洛与血管紧张素转换酶抑制剂培哚普利联合干预心梗后慢性心衰对心肌肌浆网(SR)Ca~(2+)泵活性和Ca~(2+)释放通道(RyR2)密度的影响及意义.方法通过结扎大鼠左冠脉建立慢性心衰模型,术后1周开始分别给以卡维地洛(6mg·kg~(-1)·d~(-1))、培哚普利(4mg·kg~(-1)·d~(-1))、特拉唑嗪(2mg·kg~(-1)·d~(-1))、卡维地洛(6mg·kg~(-1)·d~(-1))+培哚普利(4mg·kg~(-1)·d~(-1))联合干预9周,观察血流动力学、左室心肌SR Ca~(2+)泵活性和RyR_2密度的变化.结果与假手术组相比,心衰组左室舒张末压(LVEDP)显著升高(P<0.01),+dp/dt_(max)、-dp/dt_(max)显著降低(P<0.01),左室心肌SR Ca~(2+)泵活性和RyR_2密度显著降低(P<0.01).卡维地洛、培哚普利单独及联合干预均降低LVEDP(P<0.01),升高+dp/dt_(max)、-dp/dt_(max)(P<0.01),并升高左室心肌SR Ca~(2+)泵活性和RyR_2密度(P<0.01),联合干预变化更明显(P<0.01).特拉唑嗪组对上述指标无明显影响(P>0.05).左室心肌sRCa~(2+)泵活性与+dp/dt_(max)、-dp/dt_(max)显著正相关(r=0.596,r=0.684,P<0.01).结论 β受体阻滞剂卡维地洛和血管紧张素转换酶抑制剂培哚普利长期联合干预心梗后慢性心衰,能够改善血流动力学和心肌SR Ca~(2+)泵活性,增加RyR_2密度,优于任何单一药物干预.
목적 탐토β수체조체제잡유지락여혈관긴장소전환매억제제배타보리연합간예심경후만성심쇠대심기기장망(SR)Ca~(2+)빙활성화Ca~(2+)석방통도(RyR2)밀도적영향급의의.방법 통과결찰대서좌관맥건립만성심쇠모형,술후1주개시분별급이잡유지락(6mg·kg~(-1)·d~(-1))、배타보리(4mg·kg~(-1)·d~(-1))、특랍서진(2mg·kg~(-1)·d~(-1))、잡유지락(6mg·kg~(-1)·d~(-1))+배타보리(4mg·kg~(-1)·d~(-1))연합간예9주,관찰혈류동역학、좌실심기SR Ca~(2+)빙활성화RyR_2밀도적변화.결과 여가수술조상비,심쇠조좌실서장말압(LVEDP)현저승고(P<0.01),+dp/dt_(max)、-dp/dt_(max)현저강저(P<0.01),좌실심기SR Ca~(2+)빙활성화RyR_2밀도현저강저(P<0.01).잡유지락、배타보리단독급연합간예균강저LVEDP(P<0.01),승고+dp/dt_(max)、-dp/dt_(max)(P<0.01),병승고좌실심기SR Ca~(2+)빙활성화RyR_2밀도(P<0.01),연합간예변화경명현(P<0.01).특랍서진조대상술지표무명현영향(P>0.05).좌실심기sRCa~(2+)빙활성여+dp/dt_(max)、-dp/dt_(max)현저정상관(r=0.596,r=0.684,P<0.01).결론 β수체조체제잡유지락화혈관긴장소전환매억제제배타보리장기연합간예심경후만성심쇠,능구개선혈류동역학화심기SR Ca~(2+)빙활성,증가RyR_2밀도,우우임하단일약물간예.
Objective 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. Methods 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. Results 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 SRCa~(2+)pump and density of RyR2 (P<0.01). Both monotherapies with carvedilol and perindopril attenuated the increment ofLVEDP, 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). Conclusion Prolonged treatment with p$-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.