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目的探讨血管紧张素转化酶抑制剂培哚普利在心力衰竭治疗中对心肌细胞收缩力-频率关系的影响及其可能机制。方法通过缩窄雄性Wistar大鼠的腹主动脉制成压力负荷增高性心力衰竭模型。随机分成培哚普利治疗组(CHF-T,每日3mg/kg体重)、心衰对照组(CHF-C)和假手术对照组(PS)。分离左室心肌细胞,应用激光扫描共聚焦显微镜测定单个心肌细胞在0．5、1．0、1．5、2．0 Hz电刺激时的缩短分数及钙瞬变。结果心肌细胞的收缩力-频率关系,在CHF-C组由PS组的正负双向型转变为单纯负向型,而在CHF-T组呈平坦型。心肌细胞的钙-频率关系在PS和CHF-C组与收缩力-频率关系相似,分别呈正负双向型和单纯负向性；而在CHF-T组也为正负双向型,但其[Ca~(2+)]imax峰刺激频率却由PS组的1．5Hz前移到1．0Hz。另外,在不考虑刺激频率的情况下,于PS和CHF-C组,心肌细胞的缩短分数与[Ca~(2+)]imax有明显的相关性,而在CHF-T组则相关不明显。结论慢性心力衰竭时,单个心肌细胞的收缩力-频率关系明显受损。长程的ACE抑制剂治疗能抑制上述改变。
Objective To investigate the effect of perindopril, an angiotensin converting enzyme inhibitor, on the contractility-frequency relationship of cardiomyocytes in the treatment of heart failure and its possible mechanism. Methods The model of stress-overload heart failure was made by narrowing the abdominal aorta of male Wistar rats. Patients were randomly assigned to receive either perindopril (CHF-T, 3 mg / kg body weight daily), CHF-C, and sham control (PS). Left ventricular myocardial cells were isolated and the shortening fraction and calcium transient of single cardiomyocytes at 0.5, 1.0, 1.5 and 2.0 Hz electrical stimulation were measured by laser scanning confocal microscopy. Results The contractility-frequency relationship of cardiomyocytes was changed from positive and negative bidirectional type in PSF group to pure negative type in CHF-C group, and flat in CHF-T group. The calcium-frequency relationship in cardiomyocytes was similar to contractility-frequency in PS and CHF-C groups, showing positive and negative bi-directional and pure negative, respectively, but also positive and negative in CHF-T group [ Ca ~ (2 +)] imax peak stimulation frequency was moved forward from 1.5Hz PS group to 1.0Hz. In addition, shortening fraction of cardiomyocytes was significantly correlated with [Ca ~ (2 +)] imax in PS and CHF-C group, but not in CHF-T group, irrespective of stimulation frequency . Conclusion In chronic heart failure, the contractility-frequency relationship of single cardiomyocytes was significantly impaired. Long-term ACE inhibitor treatment can inhibit the above changes.