Parratt J R
Br J Pharmacol. 1974 May;51(1):5-13. doi: 10.1111/j.1476-5381.1974.tb09625.x.
1 Haemodynamic changes have been studied in cats after the chronic oral administration of oxyfedrine (14 mg/kg for 3-4 weeks) or of placebo (lactose). The initial part of the study was carried out under double-blind conditions. The arterial blood pressure was between 19 mmHg (diastolic) and 27 mmHg (systolic) higher in the oxyfedrine treated animals, but there were no differences between the two groups with regard to cardiac output, left ventricular dP/dt max, heart rate or systolic ejection time.2 In cats similarly treated with propranolol (4 mg/kg) there was a slight (12%), but significant, reduction in cardiac output.3 Isoprenaline dose-response curves were shifted to the right in the cats administered oxyfedrine as well as in those administered propranolol. The degree of shift was five-fold (positive chronotropic response) and 20-fold (decrease in diastolic blood pressure) in the oxyfedrine group and 10- and 80-fold, respectively, in the propranolol group.4 In contrast to the partial blockade of the effects of isoprenaline, the haemodynamic response to oxyfedrine was largely unaltered, both in the cats pretreated with propranolol and in those pretreated with oxyfedrine. The pressor response to noradrenaline was potentiated in the cats pretreated with oxyfedrine.5 These results provide an explanation for the anti-anginal action of oxyfedrine. Some degree of beta-adrenoceptor blockade is achieved without a reduction in cardiac output or left ventricular dP/dt max. The relevance of these findings to the haemodynamic situation in angina is discussed.
1 对猫长期口服奥昔非君(14毫克/千克,持续3 - 4周)或安慰剂(乳糖)后的血流动力学变化进行了研究。研究的初始阶段在双盲条件下进行。接受奥昔非君治疗的动物的动脉血压舒张压升高19毫米汞柱,收缩压升高27毫米汞柱,但两组在心输出量、左心室dp/dt最大值、心率或收缩期射血时间方面没有差异。
2 用普萘洛尔(4毫克/千克)进行类似治疗的猫的心输出量有轻微(12%)但显著的降低。
3 异丙肾上腺素剂量反应曲线在给予奥昔非君的猫以及给予普萘洛尔的猫中均向右移动。奥昔非君组的移动程度为五倍(正性变时反应)和20倍(舒张压降低),普萘洛尔组分别为10倍和80倍。
4 与异丙肾上腺素作用的部分阻断相反,在预先用普萘洛尔治疗的猫和预先用奥昔非君治疗的猫中,对奥昔非君的血流动力学反应基本未改变。预先用奥昔非君治疗的猫对去甲肾上腺素的升压反应增强。
5 这些结果为奥昔非君的抗心绞痛作用提供了解释。在不降低心输出量或左心室dp/dt最大值的情况下实现了一定程度的β - 肾上腺素能受体阻断。讨论了这些发现与心绞痛血流动力学情况的相关性。