Watanabe K, Kimura Y, Abiko Y
Arch Int Pharmacodyn Ther. 1986 Dec;284(2):297-312.
Rat hearts were perfused by means of the Langendorff's technique and paced at 150/min. Oxygen saturation level of myocardial myoglobin was measured continuously according to an optical method, by which the intracellular oxygen level in the myocardial cells can be monitored continuously. Krebs-Henseleit solution was bubbled with a gas mixture containing either 95% O2 + 5% CO2 (high oxygen solution) or 95% N2 + 5% CO2 (anoxic solution), or both (low oxygen solution). Hypoxia was produced by changing the perfusion fluid from high to low oxygen solution. After 10 min of hypoxia, drugs were infused into the inflow tube at a rate of 0.1 ml/min for 10 min. Hypoxia increased coronary flow by about 25%, decreased oxygen saturation level of myoglobin by 23.1-35.7%, without a marked change in left ventricular pressure. Nifedipine (1.0 microgram/ml) increased oxygen saturation level, which had been reduced by hypoxia, by 16-27%. Nifedipine at the concentration of 0.1 microgram/ml also increased the oxygen saturation level of myocardial myoglobin slightly, but at the concentration of 10 micrograms/ml it decreased. Nitroglycerin (100 micrograms/kg) increased the oxygen saturation level, which had been decreased by hypoxia, by 6-8%, whereas dipyridamole (100 micrograms/ml) did not. It is concluded that nifedipine as well as nitroglycerin can increase the oxygen saturation level of myocardial myoglobin during hypoxia, suggesting that both drugs may increase the intracellular oxygen tension in the hypoxic heart.
采用Langendorff技术对大鼠心脏进行灌注，并以每分钟150次的频率起搏。通过光学方法连续测量心肌肌红蛋白的氧饱和度水平，借此可对心肌细胞内的氧水平进行连续监测。用含有95% O₂ + 5% CO₂的气体混合物（高氧溶液）、95% N₂ + 5% CO₂的气体混合物（缺氧溶液）或两者（低氧溶液）对Krebs-Henseleit溶液进行鼓泡。通过将灌注液从高氧溶液改为低氧溶液来制造缺氧状态。缺氧10分钟后，以0.1毫升/分钟的速率将药物注入流入管，持续10分钟。缺氧使冠状动脉血流量增加约25%，使肌红蛋白的氧饱和度水平降低23.1 - 35.7%，而左心室压力无明显变化。硝苯地平（1.0微克/毫升）使因缺氧而降低的氧饱和度水平提高了16 - 27%。浓度为0.1微克/毫升的硝苯地平也使心肌肌红蛋白的氧饱和度水平略有提高，但浓度为10微克/毫升时则使其降低。硝酸甘油（100微克/千克）使因缺氧而降低的氧饱和度水平提高了6 - 8%，而双嘧达莫（100微克/毫升）则没有。结论是，硝苯地平和硝酸甘油均可在缺氧期间提高心肌肌红蛋白的氧饱和度水平，这表明这两种药物可能会增加缺氧心脏中的细胞内氧张力。
