Tsukube T, McCully J D, Federman M, Krukenkamp I B, Levitsky S
Division of Cardiothoracic Surgery, New England Deaconess Hospital and Harvard Medical School, Boston, MA, USA.
J Thorac Cardiovasc Surg. 1996 Jul;112(1):175-84. doi: 10.1016/s0022-5223(96)70194-0.
The effect of cardioplegic solutions with high concentrations of potassium or magnesium (or both) on cytosolic calcium accumulation was investigated with fura-2 in isolated perfused mature (n = 24) and aged (n = 24) rabbit hearts.
We compared cytosolic calcium accumulation before ischemia (control), during 30 minutes of ischemia and 30 minutes of reperfusion under global ischemia, or after treatment with potassium (20 mmol/L), magnesium (20 mmol/L), or both.
Cytosolic calcium accumulation was increased during global ischemia in the mature heart (from 178.7 +/- 24.2 in the control group to 393.6 +/- 25.5 nmol/L; p < 0.005) and in the aged heart (from 187.4 +/- 18.7 in the control group to 501.0 +/- 46.1 nmol/L; p < 0.005). Potassium reduced cytosolic calcium accumulation during ischemia in both the mature and aged hearts (300.9 +/- 23.2 and 365.2 +/- 27.7 nmol/L, respectively; p < 0.05 vs global ischemia). Magnesium and potassium/magnesium completely controlled cytosolic calcium accumulation in the mature heart (198.7 +/- 27.5 nmol/L; p < 0.01 vs global ischemia and p < 0.05 vs potassium: 182.3 +/- 22.7 nmol/L; p < 0.05 vs global ischemia and potassium, respectively). Magnesium and potassium/magnesium attenuated cytosolic calcium accumulation in the aged heart (261.3 +/- 26.7, 262.3 +/- 25.2 nmol/L, respectively; p < 0.01 vs global ischemia). These changes in cytosolic calcium accumulation correlated with improved post-ischemic ventricular function. To investigate the mechanism(s) of magnesium-supplemented cardioplegic inhibition of cytosolic calcium accumulation, we performed parallel studies (n = 43) using nifedipine, ryanodine, and dimethylthiourea. Nifedipine with or without ryanodine reduced cytosolic calcium accumulation. Dimethylthiourea did not alter cytosolic calcium accumulation during global ischemia. Our results suggest that cytosolic calcium accumulation during global ischemia was mainly increased via the sarcolemmal 1-type calcium channel and the sarcoplasmic reticulum calcium-release channel. The modulating action of potassium/magnesium cardioplegia on cytosolic calcium accumulation during ischemia would appear to act through the inhibition of the myocardial 1-type calcium channel and the sarcoplasmic reticulum calcium-release channel.
Senescent cardiac dysfunction correlates with increased ischemia-induced cytosolic calcium accumulation. Magnesium-supplemented potassium cardioplegia ameliorates this age-related phenomenon at normothermia and may have important implications in myocardial protection in the elderly population.
采用fura-2荧光探针，在离体灌注的成年（n = 24）和老年（n = 24）兔心脏中，研究高浓度钾或镁（或两者兼具）的心脏停搏液对胞质钙积聚的影响。
比较缺血前（对照）、全心缺血30分钟及再灌注30分钟期间，或经钾（20 mmol/L）、镁（20 mmol/L）或两者处理后的胞质钙积聚情况。
全心缺血期间，成年心脏的胞质钙积聚增加（对照组从178.7±24.2增加至393.6±25.5 nmol/L；p < 0.005），老年心脏也如此（对照组从187.4±18.7增加至501.0±46.1 nmol/L；p < 0.005）。钾可减少成年和老年心脏缺血期间的胞质钙积聚（分别为300.9±23.2和365.2±27.7 nmol/L；与全心缺血相比，p < 0.05）。镁及钾/镁可完全控制成年心脏的胞质钙积聚（198.7±27.5 nmol/L；与全心缺血相比，p < 0.01；与钾相比，p < 0.05：182.3±22.7 nmol/L；分别与全心缺血及钾相比，p < 0.05）。镁及钾/镁可减轻老年心脏的胞质钙积聚（分别为261.3±26.7、262.3±25.2 nmol/L；与全心缺血相比，p < 0.01）。这些胞质钙积聚的变化与缺血后心室功能的改善相关。为研究补充镁的心脏停搏液抑制胞质钙积聚的机制，我们使用硝苯地平、ryanodine和二甲基硫脲进行了平行研究（n = 43）。单独或联合ryanodine使用硝苯地平均可减少胞质钙积聚。二甲基硫脲在全心缺血期间未改变胞质钙积聚。我们的结果表明，全心缺血期间胞质钙积聚主要通过肌膜L型钙通道和肌浆网钙释放通道增加。钾/镁心脏停搏液对缺血期间胞质钙积聚的调节作用似乎是通过抑制心肌L型钙通道和肌浆网钙释放通道实现的。
衰老性心脏功能障碍与缺血诱导的胞质钙积聚增加相关。补充镁的钾心脏停搏液在常温下可改善这种与年龄相关的现象，可能对老年人群的心肌保护具有重要意义。
