Ko T, Otani H, Imamura H, Omori K, Inagaki C
Department of Thoracic and Cardiovascular Surgery, Kansai Medical University, Osaka, Japan.
J Thorac Cardiovasc Surg. 1995 Jul;110(1):103-10. doi: 10.1016/S0022-5223(05)80015-7.
Na+/K+ adenosinetriphosphatase (sodium pump) may play a key role in the prevention of reperfusion injury caused by Ca2+ overload. The present study was undertaken to investigate the role of sodium pump activity in warm induction of cardioplegia combined with reperfusion of oxygenated cardioplegic solution. Isolated and perfused rat hearts were subjected to 15 minutes of normothermic ischemia to produce a model of severely failing heart. The hearts then received myocardial preservation. Warm (37 degrees C) or cold (4 degrees C) oxygenated modified St. Thomas' Hospital solution was given for 5 minutes before and after 120 minutes of hypothermic cardioplegic arrest. Reduced myocardial pH during normothermic ischemia was adjusted toward the baseline level by administration of cold or warm oxygenated cardioplegic solution without a significant intergroup difference. Myocardial adenosine triphosphate levels decreased to less than 30% of the preischemic level during 15 minutes of normothermic ischemia, but were increased partly by induction of cold or warm oxygenated cardioplegia. Thus these metabolic indices failed to demonstrate the superiority of warm over cold oxygenated cardioplegia. Na+/K+ adenosinetriphosphatase activity in the membrane fraction was significantly stimulated by a cardioplegic dose of K+ with maximum activity at 16 mEq/L. The enzyme activity of the heart measured after normothermic ischemia was reduced to less than 50% of that in the nonischemic heart. Although warm induction of cardioplegia and reperfusion of oxygenated cardioplegic solution maintained Na+/K+ adenosinetriphosphatase activity at the preischemic level, the enzyme activity was abolished at 4 degrees C, which is the temperature used in cold cardioplegia. A subtoxic dose of ouabain (0.1 mmol/L) inhibited the enzyme activity of the heart undergoing this preservation regimen to approximately 50%. Warm induction and reperfusion of oxygenated cardioplegic solution showed significantly better recovery of isovolumic left ventricular function during reperfusion compared with that obtained with cold oxygenated cardioplegia. However, the beneficial effect of warm oxygenated cardioplegia on left ventricular function was compromised by inclusion of 0.1 mmol/L ouabain without a significant effect on myocardial metabolic parameters. These results suggest that stimulation of Na+ pump activity may account for the beneficial effect of warm induction and reperfusion of oxygenated cardioplegic solution in the energy-depleted heart.
钠钾三磷酸腺苷酶（钠泵）可能在预防钙超载引起的再灌注损伤中起关键作用。本研究旨在探讨钠泵活性在温诱导心脏停搏联合氧合心脏停搏液再灌注中的作用。将离体灌注的大鼠心脏进行15分钟的常温缺血，以建立严重衰竭心脏模型。然后对心脏进行心肌保护。在低温心脏停搏120分钟前后，给予温（37℃）或冷（4℃）氧合改良圣托马斯医院溶液5分钟。常温缺血期间降低的心肌pH值通过给予冷或温氧合心脏停搏液调整至基线水平，组间无显著差异。常温缺血15分钟期间，心肌三磷酸腺苷水平降至缺血前水平的30%以下，但通过诱导冷或温氧合心脏停搏可部分升高。因此，这些代谢指标未能显示温氧合心脏停搏优于冷氧合心脏停搏。膜组分中的钠钾三磷酸腺苷酶活性受到心脏停搏剂量的钾的显著刺激，在16 mEq/L时活性最高。常温缺血后测定的心脏酶活性降至非缺血心脏的50%以下。虽然温诱导心脏停搏和氧合心脏停搏液再灌注可将钠钾三磷酸腺苷酶活性维持在缺血前水平，但在4℃（冷心脏停搏所用温度）时酶活性被消除。亚毒性剂量的哇巴因（0.1 mmol/L）将接受该保存方案的心脏的酶活性抑制至约50%。与冷氧合心脏停搏相比，温诱导和氧合心脏停搏液再灌注在再灌注期间显示出左心室等容功能的恢复明显更好。然而，加入0.1 mmol/L哇巴因会损害温氧合心脏停搏对左心室功能的有益作用，而对心肌代谢参数无显著影响。这些结果表明，钠泵活性的刺激可能是温诱导和氧合心脏停搏液再灌注对能量耗竭心脏有益作用的原因。
