Hanton Gilles, Gautier Mathieux, Bonnet Pierre
Pfizer Global Research and Development, Z.I. Pocé-sur-Cisse, BP 159, 7401 Amboise Cedex, France.
Arch Toxicol. 2004 Jan;78(1):40-8. doi: 10.1007/s00204-003-0503-6. Epub 2003 Aug 23.
Doppler and M-mode echocardiography (EC) were used to investigate the effects of minoxidil on the cardiac function of the dog and potentially to clarify the pathogenesis of cardiac lesions, in particular the necrotic lesion in the left ventricle and the haemorrhagic lesion in the right atrium. Groups of three dogs were treated with a single oral dose of 0.5 or 2 mg/kg minoxidil or control vehicle, and M-mode and Doppler parameters were recorded at different time points before as well as 1, 3 and 24 h after treatment. The treatment produced a number of changes in M-mode parameters that indicate an increase in left ventricle contractility, in particular, increases in the percentage of thickening of the left ventricle wall during systole and in ejection fraction, and decrease of systolic volume. There was also a decrease in diastolic volume, which indicates a decrease in filling of the left ventricle probably due to the tachycardia and subsequent decrease in inter-systolic time. Doppler EC showed an increase in the velocity of the aortic flow, which indicates an increase in cardiac contractility. There was also a mild increase in stroke volume, which together with the tachycardia resulted in a marked increase in cardiac output. Together, Doppler and M-mode recordings gave evidence of an increase in the contractility of the left ventricle. This change is consistent with the generally accepted mechanism for the development of the left ventricle lesion induced by minoxidil. Minoxidil also produced changes in atrio-ventricular flows. The velocity and/or acceleration of E- and A-waves of the mitral and tricuspid flows increased, and the E/A ratio decreased. The changes in the E-wave indicate a faster diastole of the ventricle probably to compensate for the decrease in inter-systolic time. The changes in A wave are characteristic of an increased amplitude and velocity of the atrial contraction. This latter change is much more marked for tricuspid than for mitral flow. For both flows the E/A ratio decreased, which indicates that the contraction of the atria plays an increased role in ventricle filling after minoxidil treatment. This stimulation of atrial contraction that we evaluate with Doppler EC may play a key role in the development of the atrial lesion produced by minoxidil. The fact that the change is more marked in the right than in the left atrium may explain why the lesion occurs only in the right atrium in dogs. This study showed, therefore, that Doppler EC associated with M-mode EC is a useful method for obtaining pertinent information on the pathogenesis of the left ventricle lesion induced by haemodynamic mechanisms. Moreover, Doppler EC allowed the assessment of changes in the function of the right atrium that may be involved in the development of the right atrial lesion.
采用多普勒和M型超声心动图（EC）研究米诺地尔对犬心功能的影响，并试图阐明心脏病变的发病机制，尤其是左心室坏死性病变和右心房出血性病变的发病机制。将每组三只犬分别给予0.5或2mg/kg米诺地尔的单次口服剂量或对照赋形剂，并在治疗前以及治疗后1、3和24小时的不同时间点记录M型和多普勒参数。治疗引起了M型参数的一些变化，这些变化表明左心室收缩力增加，特别是左心室壁在收缩期增厚百分比和射血分数增加，以及收缩末期容积减小。舒张末期容积也减小，这表明左心室充盈减少可能是由于心动过速以及随后的收缩间期缩短所致。多普勒EC显示主动脉血流速度增加，这表明心脏收缩力增加。每搏输出量也有轻度增加，这与心动过速一起导致心输出量显著增加。总之，多普勒和M型记录证明了左心室收缩力增加。这种变化与米诺地尔诱导的左心室病变发展的普遍接受机制一致。米诺地尔还引起房室血流的变化。二尖瓣和三尖瓣血流的E波和A波的速度和/或加速度增加，E/A比值降低。E波的变化表明心室舒张更快，可能是为了补偿收缩间期的缩短。A波的变化表现为心房收缩幅度和速度增加。后一种变化在三尖瓣血流中比在二尖瓣血流中更为明显。对于两种血流，E/A比值均降低，这表明米诺地尔治疗后心房收缩在心室充盈中发挥了更大的作用。我们用多普勒EC评估的这种心房收缩刺激可能在米诺地尔引起的心房病变发展中起关键作用。这种变化在右心房比在左心房更明显这一事实可能解释了为什么犬只的病变仅发生在右心房。因此，本研究表明，与M型EC相关的多普勒EC是一种有用的方法，可用于获取有关血流动力学机制诱导的左心室病变发病机制的相关信息。此外，多普勒EC可以评估右心房功能的变化，这些变化可能与右心房病变的发展有关。
