Faulk E A, McCully J D, Hadlow N C, Tsukube T, Krukenkamp I B, Federman M, Levitsky S
Division of Cardiothoracic Surgery, New England Deaconess Hospital, Boston, MA 02215, USA.
Circulation. 1995 Nov 1;92(9 Suppl):II405-12. doi: 10.1161/01.cir.92.9.405.
The aged myocardium accumulates significantly more cytosolic calcium [Ca2+]i during ischemia, and functional recovery is more severely compromised as compared with the mature heart. Cardioplegia ameliorates these phenomena. The mechanism by which increased calcium accumulation reduces functional recovery in the senescent myocardium is unknown, but it has been suggested that futile calcium cycling in the mitochondria leading to depletion of ATP stores during normothermic global ischemia may be involved.
To investigate the effect of cardioplegia on mitochondrial calcium ([Ca2+]mt) accumulation and the expression of cytochrome oxidase I (COX I) during global ischemia, mitochondria were isolated from mature (age, 15 to 20 weeks) and aged (age > 130 weeks) rabbit hearts after Langendorff perfusion. Five perfused heart groups were investigated: 30 minutes of global ischemia without treatment (control), with potassium (K, 20 mmol/L), magnesium (Mg, 20 mmol/L), or potassium and magnesium (K/Mg) cardioplegia. No significant difference in [Ca2+]mt was evident in mature hearts with any protocol. In aged hearts, [Ca2+]mt was increased in global ischemia but was ameliorated with Mg and K/Mg cardioplegia. COX I mRNA levels in aged hearts were lower in both control and global ischemia but were increased with cardioplegia. Maximal velocities for COX I were significantly increased with Mg cardioplegia both in the mature and the aged myocardium.
K and/or Mg cardioplegia ameliorates [Ca2+]mt accumulation in aged hearts during normothermic global ischemia and increases COX I mRNA levels to a level not significantly different from that found in mature hearts.
与成熟心脏相比，老年心肌在缺血期间胞质钙[Ca2+]i显著蓄积更多，且功能恢复受到更严重损害。心脏停搏可改善这些现象。老年心肌中钙蓄积增加导致功能恢复降低的机制尚不清楚，但有研究提示，在常温全心缺血期间，线粒体中无效的钙循环导致ATP储备耗竭可能与之有关。
为研究心脏停搏对全心缺血期间线粒体钙([Ca2+]mt)蓄积及细胞色素氧化酶I(COX I)表达的影响，在Langendorff灌注后，从成熟（年龄15至20周）和老年（年龄>130周）兔心脏中分离出线粒体。研究了5个灌注心脏组：未经处理（对照）、使用钾（K，20 mmol/L）、镁（Mg，20 mmol/L）或钾镁（K/Mg）心脏停搏液进行30分钟全心缺血。在任何方案下，成熟心脏的[Ca2+]mt均无显著差异。在老年心脏中，全心缺血时[Ca2+]mt增加，但镁和钾镁心脏停搏液可改善这种情况。老年心脏中COX I mRNA水平在对照和全心缺血时均较低，但心脏停搏后升高。镁心脏停搏液使成熟和老年心肌中COX I的最大速度均显著增加。
钾和/或镁心脏停搏液可改善常温全心缺血期间老年心脏中[Ca2+]mt的蓄积，并使COX I mRNA水平升高至与成熟心脏无显著差异的水平。
