Hano O, Bogdanov K Y, Sakai M, Danziger R G, Spurgeon H A, Lakatta E G
Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA.
Am J Physiol. 1995 Nov;269(5 Pt 2):H1607-12. doi: 10.1152/ajpheart.1995.269.5.H1607.
To determine whether advancing age is accompanied by a reduced Ca2+ tolerance, we measured Ca(2+)-dependent diastolic pressure, prolonged relaxation and systolic functional deterioration, spontaneous sarcoplasmic reticulum (SR)-generated Ca2+ oscillations [detected as scattered laser light intensity fluctuations (SLIF)], aftercontractions, and ventricular fibrillation in isolated, isovolumic, atrioventricular-blocked intact hearts from 24- to 26-mo (old) and 6- to 8-mo (young) male Wistar rats. In enzymatically isolated single cardiac myocytes, the likelihood of the occurrence of spontaneous contractile waves driven by spontaneous SR Ca2+ release was also determined. In response to stepwise increase in perfusate Ca2+ concentration (Cao), a reduction in the maximum developed pressure accompanied by an elevation in end-diastolic pressure and a prolonged contraction duration was observed at lower Cao in old vs. young hearts (P < 0.01 for each parameter). Furthermore, Ca(2+)-dependent ventricular fibrillation occurred during pacing in six old but in no young hearts (P < 0.01), aftercontractions were observed in seven old vs. one young heart (P < 0.01), and SLIF increased to a greater extent in old vs. young hearts. In single cardiac myocytes, spontaneous contractile waves occurred more frequently with increasing age (P < 0.01). These results indicate that aging is associated with an increased likelihood for the occurrence of SR-generated Ca2+ oscillations and functional abnormalities that result from these oscillations.
为了确定年龄增长是否伴随着钙耐受性降低，我们测量了24至26月龄（老年）和6至8月龄（年轻）雄性Wistar大鼠离体、等容、房室传导阻滞完整心脏中依赖钙的舒张压、舒张期延长和收缩功能恶化、自发肌浆网（SR）产生的钙振荡[检测为散射激光光强度波动（SLIF）]、后收缩和心室颤动。在酶解分离的单个心肌细胞中，还测定了由自发SR钙释放驱动的自发收缩波发生的可能性。随着灌注液钙浓度（Cao）逐步增加，与年轻心脏相比，老年心脏在较低的Cao水平下观察到最大舒张压降低，同时舒张末期压力升高，收缩持续时间延长（每个参数P<0.01）。此外，在起搏过程中，6只老年心脏发生了依赖钙的心室颤动，而年轻心脏未发生（P<0.01），7只老年心脏观察到后收缩，而年轻心脏只有1只（P<0.01），并且与年轻心脏相比，老年心脏中SLIF增加的程度更大。在单个心肌细胞中，自发收缩波的发生频率随着年龄的增长而增加（P<0.01）。这些结果表明，衰老与SR产生的钙振荡发生的可能性增加以及由这些振荡导致的功能异常有关。
