Matsumura H, Hara A, Abiko Y
Department of Pharmacology, Asahikawa Medical College, Japan.
Cardiovasc Drugs Ther. 1990 Jun;4(3):719-22. doi: 10.1007/BF01856560.
The effect of diltiazem on the oxymyoglobin level was studied in the isolated rat heart during hypoxia. The heart was perfused with Krebs-Henseleit solution equilibrated with a gas mixture containing 95% O2 + 5% CO2 (normoxic perfusion solution) at a constant flow rate (9 ml/min) according to Langendorff's method. All the hearts were paced at 300 beats/min. The myocardial oxymyoglobin level (i.e., intracellular oxygen level) of the left ventricular surface was continuously measured by means of an optical technique. Diltiazem (infused into the aortic cannula for 10 minutes at concentrations of 0.72, 2.41, or 4.82 microM, expressed as the final concentration in the solution) decreased the left ventricular pressure (LVP) and perfusion pressure (PP) dose dependently, and did not change the oxymyoglobin (MbO2) level during normoxic perfusion. Hypoxic perfusion (using a gas mixture containing 30% O2 + 5% CO2 + 65% N2) decreased the MbO2, LVP, and PP. Diltiazem (infused 5 minutes after the hypoxic perfusion) at a concentration of 2.41 or 4.82 microM increased the MbO2 level and further decreased the LVP, without affecting the PP. The low concentration of 2.41 or 4.82 microM increased the MbO2 level and further decreased the LVP, without affecting the PP. The low concentration (0.72 microM) of diltiazem, however, had practically no effect on these parameters. In summary, diltiazem in high concentrations decreased the LVP and increased the intracellular oxygen level of the myocardial cells during hypoxia, but not during normoxia.
在缺氧状态下，研究了地尔硫䓬对离体大鼠心脏中氧合肌红蛋白水平的影响。根据Langendorff法，心脏以恒定流速（9 ml/min）用含95% O₂ + 5% CO₂的气体混合物平衡的Krebs-Henseleit溶液灌注（常氧灌注溶液）。所有心脏均以300次/分钟的频率起搏。通过光学技术连续测量左心室表面的心肌氧合肌红蛋白水平（即细胞内氧水平）。地尔硫䓬（以0.72、2.41或4.82 μM的浓度注入主动脉插管10分钟，以溶液中的最终浓度表示）剂量依赖性地降低左心室压力（LVP）和灌注压力（PP），并且在常氧灌注期间不改变氧合肌红蛋白（MbO₂）水平。缺氧灌注（使用含30% O₂ + 5% CO₂ + 65% N₂的气体混合物）降低了MbO₂、LVP和PP。在缺氧灌注5分钟后注入的浓度为2.41或4.82 μM的地尔硫䓬增加了MbO₂水平，并进一步降低了LVP，但不影响PP。2.41或4.82 μM的低浓度增加了MbO₂水平，并进一步降低了LVP，但不影响PP。然而，低浓度（0.72 μM）的地尔硫䓬对这些参数实际上没有影响。总之，高浓度的地尔硫䓬在缺氧时降低LVP并增加心肌细胞的细胞内氧水平，但在常氧时则不然。
