Institute of Cardiovascular Sciences, St Boniface Hospital Research, Department of Physiology and Division of Cardiology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba, Canada.
J Cell Physiol. 2013 Oct;228(10):2063-70. doi: 10.1002/jcp.24373.
In order to examine the reversibility of heart failure due to myocardial infarction (MI) by β-adrenoceptor blockade, 12 weeks infarcted rats were treated with or without metoprolol (50 mg/kg/day) for 8 weeks. The depressed left ventricular (LV) systolic pressure, positive and negative rates of changes in pressure development, ejection fraction, fractional shortening and cardiac output, as well as increased LV end-diastolic pressure in 20 weeks MI animals were partially reversed by metoprolol. MI-induced decreases in septum (systolic) thickness as well as increase in LV posterior wall thickness and LV internal diameter were partially or fully reversible by metoprolol. Treatment of MI animals with metoprolol partially reversed the elevated levels of plasma norepinephrine and dopamine without affecting the elevated levels of epinephrine. Although sarcoplasmic reticular (SR) Ca(2+)-uptake, as well as protein content for SR Ca(2+)-pump and phospholamban, were reduced in the infarcted hearts; these changes were partially reversible with metoprolol. Depressed myofibrillar Ca(2+)-stimulated ATPase activity, as well as mRNA levels for SR Ca(2+)-pump, phospholamban and α-myosin heavy chain, were unaffected whereas increased mRNA level for β-myosin heavy chain was partially reversed by metoprolol. The results suggest that partial improvement of cardiac performance by β-adrenoceptor blockade at advanced stages of heart failure may be due to partial reversal of changes in SR Ca(2+)-pump function whereas partial to complete reverse cardiac remodeling may be due to partial reduction in the elevated levels of plasma catecholamines.
为了检验β肾上腺素受体阻滞剂治疗心肌梗死（MI）后心力衰竭的逆转作用，将 12 周龄的 MI 大鼠用或不用美托洛尔（50mg/kg/天）治疗 8 周。结果显示，20 周龄 MI 大鼠的左心室（LV）收缩压、压力发展的正负变化率、射血分数、分数缩短率和心输出量降低，LV 舒张末期压升高，这些变化均被美托洛尔部分逆转。MI 诱导的室间隔（收缩）厚度降低以及 LV 后壁厚度和 LV 内径增加，也被美托洛尔部分或完全逆转。美托洛尔治疗 MI 大鼠可部分逆转血浆去甲肾上腺素和多巴胺水平升高，而不影响肾上腺素水平升高。虽然肌浆网（SR）Ca2+摄取以及 SR Ca2+泵和磷蛋白的蛋白含量在梗死心脏中降低，但这些变化可被美托洛尔部分逆转。肌球蛋白 Ca2+刺激的 ATP 酶活性降低以及 SR Ca2+泵、磷蛋白和α肌球蛋白重链的 mRNA 水平降低，而 SR Ca2+泵、磷蛋白和β肌球蛋白重链的 mRNA 水平升高，美托洛尔治疗可部分逆转。结果表明，β肾上腺素受体阻滞剂在心力衰竭晚期部分改善心脏功能可能是由于 SR Ca2+泵功能的部分逆转，而部分至完全逆转心脏重构可能是由于血浆儿茶酚胺水平的部分降低。
