Smolenski R T, Jayakumar J, Seymour A M, Yacoub M H
Department of Cardiothoracic Surgery, National Heart and Lung Institute, Harefield Hospital, Middlesex, UK.
Mol Cell Biochem. 1998 Mar;180(1-2):137-43.
It is well established that severe hypertrophy induces metabolic and structural changes in the heart which result in enhanced susceptibility to ischemic damage during cardioplegic arrest while much less is known about the effect of cardioplegic arrest on moderately hypertrophied hearts. The aim of this study was to elucidate the differences in myocardial high energy phosphate metabolism and in functional recovery after cardioplegic arrest and ischemia in mildly hypertrophied hearts, before any metabolic alterations could be shown under baseline conditions. Cardiac hypertrophy was induced in rats by constriction of the abdominal aorta resulting in 20% increase in heart weight/body weight ratio (hypertrophy group) while sham operated animals served as control. In both groups, isolated hearts were perfused under normoxic conditions for 40 min followed by infusion of St.Thomas' Hospital No. 1 cardioplegia and 90 min ischemia at 25 degrees C with infusions of cardioplegia every 30 min. The changes in ATP, phosphocreatine (PCr) and inorganic phosphate (Pi) were followed by 31P nuclear magnetic resonance (NMR) spectroscopy. Systolic and diastolic function was assessed with an intraventricular balloon before and after ischemia. Baseline concentrations of PCr, ATP and Pi as well as coronary flow and cardiac function were not different between the two groups. However, after cardioplegic arrest PCr concentration increased to 61.8+/-4.9 micromol/g dry wt in the control group and to 46.3+/-2.8 micromol/g in hypertrophied hearts. Subsequently PCr, pH and ATP decreased gradually, concomitant with an accumulation of Pi in both groups. PCr was transiently restored during each infusion of cardioplegic solution while Pi decreased. PCr decreased faster after cardioplegic infusions in hypertrophied hearts. The most significant difference was observed during reperfusion: PCr recovered to its pre-ischemic levels within 2 min following restoration of coronary flow in the control group while similar recovery was observed after 4 min in the hypertrophied hearts. A greater deterioration of diastolic function was observed in hypertrophied hearts. Moderate hypertrophy, despite absence of metabolic changes under baseline conditions could lead to enhanced functional deterioration after cardioplegic arrest and ischemia. Impaired energy metabolism resulting in accelerated high energy phosphate depletion during ischemia and delayed recovery of energy equilibrium after cardioplegic arrest observed in hypertrophied hearts could be one of the underlying mechanisms.
众所周知，严重肥大可导致心脏发生代谢和结构变化，从而使心脏在心脏停搏期间对缺血损伤的易感性增强，而关于心脏停搏对中度肥大心脏的影响却知之甚少。本研究的目的是阐明轻度肥大心脏在心脏停搏和缺血后心肌高能磷酸代谢及功能恢复的差异，此时在基线条件下尚未出现任何代谢改变。通过缩窄腹主动脉诱导大鼠心脏肥大，使心脏重量/体重比增加20%（肥大组），假手术动物作为对照组。两组中，离体心脏在常氧条件下灌注40分钟，随后输注圣托马斯医院1号心脏停搏液，并在25℃下缺血90分钟，每30分钟输注一次心脏停搏液。通过31P核磁共振波谱法跟踪ATP、磷酸肌酸（PCr）和无机磷酸盐（Pi）的变化。在缺血前后用心室内球囊评估收缩和舒张功能。两组之间PCr、ATP和Pi的基线浓度以及冠状动脉血流和心脏功能无差异。然而，心脏停搏后，对照组PCr浓度增加至61.8±4.9微摩尔/克干重，肥大心脏中增加至46.3±2.8微摩尔/克。随后，PCr、pH和ATP逐渐降低，同时两组中Pi均积累。在每次输注心脏停搏液时，PCr短暂恢复，而Pi降低。肥大心脏在输注心脏停搏液后PCr下降更快。在再灌注期间观察到最显著的差异：对照组冠状动脉血流恢复后2分钟内PCr恢复到缺血前水平，而肥大心脏在4分钟后观察到类似的恢复。肥大心脏中观察到舒张功能的更大恶化。尽管在基线条件下没有代谢变化，但中度肥大可能导致心脏停搏和缺血后功能恶化加剧。肥大心脏中观察到的能量代谢受损导致缺血期间高能磷酸盐加速消耗以及心脏停搏后能量平衡恢复延迟可能是潜在机制之一。
