Fukunami M, Hearse D J
Cardiovasc Res. 1985 Feb;19(2):95-103. doi: 10.1093/cvr/19.2.95.
An isolated working rat heart preparation was used to characterise the temperature-dependency of the anti-ischaemic properties of nifedipine. In this study hearts were subjected to pre-ischaemic infusion with the St Thomas' cardioplegic solution with or without added nifedipine (0.075 mumol X litre-1). Hearts were then rendered globally ischaemic for various periods, (35, 42, 48, 56, 55, 65, 80, 105 or 130 min) at various temperatures (37.0, 35.5, 34.0, 32.5, 31.0, 29.0, 27.0, 24.0 or 20.0 degrees C, respectively). The duration of ischaemia at each temperature was selected to produce a post-ischaemic (37 degrees C) recovery of aortic flow that was approximately 50% of its pre-ischaemic (37 degrees C) control. In addition to functional indices (aortic flow, cardiac output, coronary flow, aortic pressure and heart rate) creatine kinase leakage during reperfusion was measured. At all temperatures at or above 31 degrees C the addition of nifedipine enhanced significantly (maximal value = 43%) the post-ischaemic recovery of aortic flow and other indices of pump function, while at the same time reducing significantly (by up to 56%) enzyme leakage. At ischaemic temperatures below 31 degrees C nifedipine failed to afford any significant additional protection when assessed functionally or enzymatically. It would therefore appear that hypothermia either blocks the action of nifedipine or, by acting on some common mechanism, renders the actions of the drug redundant.
采用离体工作大鼠心脏标本，以表征硝苯地平抗缺血特性的温度依赖性。在本研究中，心脏在缺血前用含或不含硝苯地平（0.075 μmol·L⁻¹）的圣托马斯心脏停搏液灌注。然后，心脏在不同温度（分别为37.0、35.5、34.0、32.5、31.0、29.0、27.0、24.0或20.0℃）下进行不同时长（35、42、48、56、55、65、80、105或130分钟）的全心缺血。选择每个温度下的缺血时长，以使缺血后（37℃）主动脉血流恢复至缺血前（37℃）对照值的约50%。除功能指标（主动脉血流、心输出量、冠脉血流、主动脉压和心率）外，还测量了再灌注期间肌酸激酶的漏出量。在31℃及以上的所有温度下，添加硝苯地平可显著增强（最大值 = 43%）缺血后主动脉血流的恢复及其他泵功能指标，同时显著减少（最多达56%）酶漏出。在低于31℃的缺血温度下，从功能或酶学角度评估，硝苯地平未能提供任何显著的额外保护。因此，低温似乎要么阻断了硝苯地平的作用，要么通过作用于某些共同机制，使该药物的作用变得多余。
