Bak M I, Wei J Y, Ingwall J S
NMR Laboratory for Physiological Chemistry, Department of Medicine, Brigham and Women's Hospital and Division of Gerontology, Beth Israel Deacones Medical Center Harvard Medical School, Boston, MA 02115, USA.
J Mol Cell Cardiol. 1998 Mar;30(3):661-72. doi: 10.1006/jmcc.1997.0633.
To test the hypotheses that aged myocardium has lower ATP concentration and that a greater ATP hydrolysis during hypoxia exaggerates diastolic dysfunction in aged myocardium, we used 31P NMR spectroscopy to measure ATP and phosphocreatine (PCr) contents combined with heart function at baseline and during hypoxia and reoxygenation in perfused hearts isolated from young adult (3-4 months old) and old (24-25 months old) Fisher 344 rats. At baseline, old hearts had 30% lower heart rate and prevalent supraventricular arrhythmia; they had lower PCr and creatine contents (approximately 30%) but normal ATP content. Hypoxia caused similar decreases in heart rate and rate pressure product in young and old hearts. There was a two-fold increase in left-ventricular end-diastolic pressure (LVEDP) in young adults, but, surprisingly, no change in LVEDP in old hearts. ATP decreased similarly in hearts from young and old rats, but the PCr decrease was two-fold smaller in old hearts during hypoxia. Superimposition of pacing on hypoxic old hearts caused six-fold increase in LVEDP; although utilization of PCr increased, it was still incomplete. We conclude that PCr is incompletely used to maintain ATP level during hypoxia especially in the senescent heart, and that the increase in LVEDP in old hearts cannot be explained solely by changes in indices of bioenergetics.
衰老心肌的三磷酸腺苷（ATP）浓度较低，且缺氧时更大程度的ATP水解会加剧衰老心肌的舒张功能障碍，我们使用磷-31核磁共振波谱法（31P NMR）测量了从年轻成年（3 - 4个月大）和老年（24 - 25个月大）的Fisher 344大鼠分离出的灌注心脏在基线、缺氧及复氧期间的ATP和磷酸肌酸（PCr）含量，并结合心脏功能进行研究。在基线时，老年心脏的心率降低30%，且普遍存在室上性心律失常；它们的PCr和肌酸含量较低（约30%），但ATP含量正常。缺氧导致年轻和老年心脏的心率及心率血压乘积出现类似程度的下降。年轻成年大鼠的左心室舒张末期压力（LVEDP）增加了两倍，但令人惊讶的是，老年心脏的LVEDP没有变化。年轻和老年大鼠心脏中的ATP下降程度相似，但在缺氧期间，老年心脏中PCr的下降幅度小两倍。对缺氧的老年心脏进行起搏会使LVEDP增加六倍；尽管PCr的利用增加了，但仍不完整。我们得出结论，在缺氧期间，尤其是在衰老心脏中，PCr不能完全用于维持ATP水平，并且老年心脏中LVEDP的增加不能仅由生物能量学指标的变化来解释。
