Tsukube T, McCully J D, Faulk E A, Federman M, LoCicero J, Krukenkamp I B, Levitsky S
Division of Cardiothoracic Surgery, New England Deaconess Hospital, Boston, Ma 02215.
Ann Thorac Surg. 1994 Oct;58(4):1005-11. doi: 10.1016/0003-4975(94)90445-6.
Previous reports have indicated that the senescent myocardium is less tolerant to surgically induced ischemia and that diminished functional recovery is associated with alterations in cytosolic calcium ([Ca2+]i) accumulation. Recently, increased [Ca2+]i has been suggested to alter nuclear calcium ([Ca2+]n) accumulation. To investigate the relation between [Ca2+]i and [Ca2+]n, we subjected mature and aged rabbit hearts to normothermic global ischemia, either without treatment or after treatment with potassium cardioplegia, magnesium cardioplegia, or a combination of potassium and magnesium cardioplegia. The relation between altered [Ca2+]n and DNA fragmentation was also investigated. Our results indicate that [Ca2+]i was increased during 30 minutes of normothermic global ischemia without treatment in both the mature and aged hearts (p < 0.05). Accumulation of [Ca2+]i during global ischemia was reduced with the use of potassium, magnesium, and a combination of potassium and magnesium cardioplegia (p < 0.05 versus untreated ischemia) in both the mature and aged hearts. Levels of [Ca2+]n were unaffected by global ischemia or cardioplegia in the mature myocardium; however, in the aged myocardium, [Ca2+]n was increased during global ischemia and with potassium cardioplegia and was associated with increased nuclear DNA fragmentation (p < 0.05). The use of magnesium and a combination of potassium and magnesium cardioplegia attenuated [Ca2+]n accumulation and nuclear DNA fragmentation (p < 0.05). Control of [Ca2+]i and [Ca2+]n was associated with enhanced functional recovery during reperfusion. These results indicate that during normothermic ischemia, there is increased [Ca2+]i and [Ca2+]n in the aged myocardium, and increased [Ca2+]n is associated with increased nuclear DNA fragmentation.(ABSTRACT TRUNCATED AT 250 WORDS)
先前的报告表明，衰老的心肌对手术诱导的缺血耐受性较差，功能恢复减弱与胞质钙（[Ca2+]i）积累的改变有关。最近，有人提出[Ca2+]i升高会改变核钙（[Ca2+]n）的积累。为了研究[Ca2+]i与[Ca2+]n之间的关系，我们对成熟和老年兔心脏进行了常温全心缺血实验，实验分为未处理组以及钾停搏液、镁停搏液或钾镁联合停搏液处理组。同时还研究了[Ca2+]n改变与DNA片段化之间的关系。我们的结果表明，在未处理的成熟和老年心脏常温全心缺血30分钟期间，[Ca2+]i均升高（p<0.05）。在成熟和老年心脏中，使用钾、镁以及钾镁联合停搏液可减少全心缺血期间[Ca2+]i的积累（与未处理的缺血相比，p<0.05）。成熟心肌中的[Ca2+]n水平不受全心缺血或停搏液的影响；然而，在老年心肌中，全心缺血期间以及使用钾停搏液时[Ca2+]n升高，且与核DNA片段化增加有关（p<0.05）。使用镁以及钾镁联合停搏液可减轻[Ca2+]n的积累和核DNA片段化（p<0.05）。控制[Ca2+]i和[Ca2+]n与再灌注期间功能恢复增强有关。这些结果表明，在常温缺血期间，老年心肌中的[Ca2+]i和[Ca2+]n升高，且[Ca2+]n升高与核DNA片段化增加有关。（摘要截断于250字）
