Hanton G, Lodola A
PFIZER Research Centre, Amboise, France.
Lab Anim. 1998 Apr;32(2):183-90. doi: 10.1258/002367798780600034.
We used echocardiography to investigate the changes in the cardiac function of dogs treated with minoxidil (a vasodilator, administered at doses which can produce mild lesions in the myocardium of the left ventricle) and quinidine (an antiarrhythmic at doses up to 8 times the upper limit of the therapeutic range in dogs). Groups of three beagles received a single administration of minoxidil at doses of 0.5 or 2 mg/kg. Two groups of two dogs received a single administration of quinidine at doses of 80 or 160 mg/kg. Two groups of three control dogs were treated concurrently with the vehicle alone. M-mode echocardiography was performed under two-dimensional echocardiography guidance on three occasions the day before treatment, immediately before dosing and 1, 3 and 24 h after dosing. We measured or calculated end diastolic, end systolic, and stroke volumes (EDV, ESV and SV), fractional shortening (FS), ejection fraction (EF), the percentage of thickening of the septum and of the left ventricle posterior wall (PST and PWT), and the mean and maximal velocities of the left ventricle posterior wall (PWVm and PWVM). At the same time as echocardiography recording, heart rate was measured by cardiac auscultation. Minoxidil produced a marked tachycardia. Less marked increases in heart rate occurred after quinidine. Both compounds were associated with a decrease in ESV and with marked increases in FS, EF, PWVm and PWVM which, in comparison with data for controls, are indicative of an increase in the amplitude and velocity of cardiac contraction. Both drugs also produced a decrease in EDV and consequently there was no increase in SV despite the increased amplitude of ventricular contraction. Cardiac output increased in proportion to the increase in heart rate. Overall, the effects were dose-related and are consistent with the pharmacological properties of the compounds. However, to date these effects have been demonstrated only by invasive methods. To conclude, we have shown that echocardiography allows a non-invasive investigation of the cardiac effects of suprapharmacological doses of antiarrhythmics and of the changes in heart function induced by vasodilators known to cause left ventricular lesions in dogs.
我们使用超声心动图来研究用米诺地尔(一种血管扩张剂,以能在左心室心肌产生轻度病变的剂量给药)和奎尼丁(一种抗心律失常药,剂量高达犬类治疗范围上限的8倍)治疗的犬类心脏功能的变化。每组三只比格犬接受0.5或2mg/kg剂量的米诺地尔单次给药。两组两只犬接受80或160mg/kg剂量的奎尼丁单次给药。两组三只对照犬同时仅用赋形剂治疗。在治疗前一天、给药前即刻以及给药后1、3和24小时,在二维超声心动图引导下进行M型超声心动图检查三次。我们测量或计算舒张末期、收缩末期和每搏量(EDV、ESV和SV)、缩短分数(FS)、射血分数(EF)、室间隔和左心室后壁增厚百分比(PST和PWT)以及左心室后壁的平均和最大速度(PWVm和PWVM)。在进行超声心动图记录的同时,通过心脏听诊测量心率。米诺地尔引起明显的心动过速。奎尼丁给药后心率升高不太明显。两种化合物均与ESV降低以及FS、EF、PWVm和PWVM显著升高有关,与对照组数据相比,这表明心脏收缩幅度和速度增加。两种药物还导致EDV降低,因此尽管心室收缩幅度增加,但SV并未增加。心输出量与心率增加成比例增加。总体而言,这些效应与剂量相关,并且与化合物的药理特性一致。然而,迄今为止,这些效应仅通过侵入性方法得到证实。总之,我们已经表明,超声心动图能够对超药理剂量的抗心律失常药物的心脏效应以及已知会在犬类中引起左心室病变的血管扩张剂所诱导的心脏功能变化进行非侵入性研究。