Riishede L, Nielsen-Kudsk F
Odense University Hospital, Department of Anaesthesiology, Aarhus C, Denmark.
Pharmacol Toxicol. 1990 May;66(5):354-60. doi: 10.1111/j.1600-0773.1990.tb00762.x.
The pharmacodynamic myocardial effects of adrenaline, isoprenaline and dobutamine were studied in isolated, perfused and spontaneously beating rabbit hearts at hypothermic conditions. Cardiac contraction amplitude increased from the control value at 37 degrees set equal to 100% to about 165% at 22 degrees, whereas contraction velocity decreased to 52%, frequency to 30% and oxygen consumption to about 19%. At 22 degrees all drugs produced pronounced positive inotropic and chronotropic effects. Em-values related to contraction velocity, frequency and oxygen consumption were for isoprenaline 152, 98 and 136%, respectively, for adrenaline 127, 100 and 198% and for dobutamine 120, 86 and 165%, respectively. The corresponding EC50-values decreased and a marked left-shift of the log-concentration response curves was observed as an expression of increased myocardial sensitivity to the drugs. Em for contraction velocity for dobutamine was distinctly reduced at 32 and 27 degrees and for adrenaline at 27 degrees in comparison to the increase seen at 22 and 37 degrees. Em for oxygen consumption showed for all drugs an increase at decreasing temperatures. The frequency-corrected QTc-interval decreased slightly to moderately during exposure to the drugs at hypothermic conditions. None of the drugs caused arrhythmias during the experiments. Coronary flow rate decreased only moderately at the higher drug concentrations at decreased temperatures. Dobutamine and adrenaline at 37 degrees and isoprenaline at 37 and 22 degrees caused an increase of Em for oxygen consumption that was slightly less than proportional to the increase of Em for contraction velocity.
在低温条件下，对离体、灌注且能自发跳动的兔心脏研究了肾上腺素、异丙肾上腺素和多巴酚丁胺的药效学心肌效应。心脏收缩幅度从设定为100%的37℃时的对照值增加到22℃时的约165%，而收缩速度降至52%，频率降至30%，氧耗降至约19%。在22℃时，所有药物均产生明显的正性肌力和变时性效应。与收缩速度、频率和氧耗相关的Em值，异丙肾上腺素分别为152%、98%和136%，肾上腺素分别为127%、100%和198%，多巴酚丁胺分别为120%、86%和165%。相应的EC50值降低，且观察到对数浓度反应曲线明显左移，这表明心肌对药物的敏感性增加。与22℃和37℃时的增加相比，多巴酚丁胺在32℃和27℃时以及肾上腺素在27℃时收缩速度的Em明显降低。所有药物的氧耗Em均随温度降低而增加。在低温条件下接触药物期间，频率校正的QTc间期轻度至中度缩短。实验期间，没有一种药物引起心律失常。在较低温度下较高药物浓度时，冠状动脉血流速度仅适度降低。37℃时的多巴酚丁胺和肾上腺素以及37℃和22℃时的异丙肾上腺素引起的氧耗Em增加略小于与收缩速度Em增加成比例。
