Al-Shafei Ahmad I M, Wise R G, Gresham G A, Bronns G, Carpenter T A, Hall L D, Huang Christopher L-H
Herchel Smith Laboratory for Medicinal Chemistry, University of Cambridge School of Clinical Medicine, Forvie Site, Robinson Way, Cambridge CB2 2PZ, UK.
J Physiol. 2002 Jan 15;538(Pt 2):541-53. doi: 10.1113/jphysiol.2001.012856.
A non-invasive cine magnetic resonance imaging (MRI) technique was developed to allow, for the first time, detection and characterization of chronic changes in myocardial tissue volume and the effects upon these of treatment by the angiotensin-converting enzyme (ACE) inhibitor captopril in streptozotocin (STZ)-diabetic male Wistar rats. Animals that had been made diabetic at the ages of 7, 10 and 13 weeks and a captopril-treated group of animals made diabetic at the age of 7 weeks were scanned. The findings were compared with the results from age-matched controls. All animal groups (n = 4 animals in each) were consistently scanned at 16 weeks. Left and right ventricular myocardial volumes were reconstructed from complete data sets of left and right ventricular transverse sections which covered systole and most of diastole using twelve equally incremented time points through the cardiac cycle. The calculated volumes remained consistent through all twelve time points of the cardiac cycle in all five experimental groups and agreed with the corresponding post-mortem determinations. These gave consistent myocardial densities whose values could additionally be corroborated by previous reports, confirming the validity of the quantitative MRI results and analysis. The myocardial volumes were conserved in animals whose diabetes was induced at 13 weeks but were significantly increased relative to body weight in animals made diabetic at 7 and 10 weeks. Captopril treatment, which was started immediately after induction of diabetes, prevented the development of this relative hypertrophy in both the left and right ventricles. We have thus introduced and validated quantitative MRI methods in a demonstration, for the first time, of chronic myocardial changes in both the right and left ventricles of STZ-diabetic rats and their prevention by the ACE inhibitor captopril.
一种非侵入性电影磁共振成像(MRI)技术首次得以开发,用于检测和表征心肌组织体积的慢性变化,以及血管紧张素转换酶(ACE)抑制剂卡托普利对链脲佐菌素(STZ)诱导的糖尿病雄性Wistar大鼠的治疗效果。对7周、10周和13周龄时患糖尿病的动物,以及7周龄时患糖尿病并接受卡托普利治疗的动物组进行扫描。将结果与年龄匹配的对照组结果进行比较。所有动物组(每组n = 4只动物)在16周时持续接受扫描。利用心动周期中十二个等间隔的时间点,从覆盖收缩期和大部分舒张期的左右心室横断完整数据集中重建左右心室心肌体积。在所有五个实验组中,计算出的体积在心动周期的所有十二个时间点均保持一致,并且与相应的尸检测定结果相符。这些结果给出了一致的心肌密度值,其值还可得到先前报告的佐证,从而证实了定量MRI结果及分析的有效性。在13周龄时诱导糖尿病的动物中,心肌体积得以保留,但在7周龄和10周龄时患糖尿病的动物中,心肌体积相对于体重显著增加。糖尿病诱导后立即开始的卡托普利治疗可防止左右心室出现这种相对肥大。因此,我们首次在STZ糖尿病大鼠的左右心室中展示了慢性心肌变化,并通过ACE抑制剂卡托普利对其进行预防,同时引入并验证了定量MRI方法。