Takarabe Kyoumi, Okazaki Yukio, Higuchi Shinya, Murayama Junichi, Natsuaki Masafumi, Itoh Tsuyoshi
Department of Thoracic and Cardiovascular Surgery, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Asian Cardiovasc Thorac Ann. 2007 Jun;15(3):204-9. doi: 10.1177/021849230701500306.
The cardioprotective efficacy of nicorandil in cardiac surgery was determined using a surgically relevant 4-hr cardioplegic arrest model. Each isolated rabbit heart was parabiotically blood-perfused using a modified Langendorff column. The magnitude of left ventricular developed pressure and rate of change of developed pressure over time were measured before (baseline) and after ischemia. Nicorandil was administered either pre-ischemia, post-ischemia, pre/post-ischemia, or continuously (before, during, and after ischemia). The endothelium of the coronary artery was observed by scanning electron microscopy. Serum myeloperoxidase activities were also measured. Although pretreatment with nicorandil did not affect recovery of developed pressure, administration of nicorandil after ischemia, or before and after ischemia, enhanced the recovery of developed pressure. Serum myeloperoxidase activity was decreased in the pre/post-ischemia and continuous groups. Endothelial reperfusion injury decreased in all nicorandil-treated groups. Administration of nicorandil attenuated ischemia-reperfusion injury of the myocardium and coronary endothelium while ameliorating leukocyte activation. In the event of unexpected prolonged cardioplegic arrest, administration of nicorandil, even just after declamping, may improve cardiac function. However, pre-ischemia administration alone was not helpful in the heart subjected to prolonged cardioplegic arrest.
使用与手术相关的4小时心脏停搏模型确定了尼可地尔在心脏手术中的心脏保护效果。每只离体兔心均使用改良的Langendorff柱进行联体血液灌注。在缺血前（基线）和缺血后测量左心室舒张末压的大小和舒张末压随时间的变化率。尼可地尔在缺血前、缺血后、缺血前/后或持续（缺血前、缺血期间和缺血后）给药。通过扫描电子显微镜观察冠状动脉内皮。还测量了血清髓过氧化物酶活性。虽然尼可地尔预处理不影响舒张末压的恢复，但缺血后或缺血前后给予尼可地尔可增强舒张末压的恢复。缺血前/后组和持续给药组的血清髓过氧化物酶活性降低。所有尼可地尔治疗组的内皮再灌注损伤均减轻。给予尼可地尔可减轻心肌和冠状动脉内皮的缺血再灌注损伤，同时改善白细胞活化。在意外延长心脏停搏的情况下，即使在松开钳夹后立即给予尼可地尔也可能改善心脏功能。然而，单独的缺血前给药对遭受延长心脏停搏的心脏没有帮助。
