Al-Shafei Ahmad I M, Wise R G, Gresham G A, 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):555-72. doi: 10.1113/jphysiol.2001.012857.
Non-invasive magnetic resonance imaging (MRI) was used to characterize changes in left and right ventricular cardiac cycles following induction of experimental, streptozotocin (STZ)-induced, diabetes in male Wistar rats at different ages. The effects of the angiotensin-converting enzyme (ACE) inhibitor captopril upon such chronic physiological changes were then evaluated, also for the first time. Diabetes was induced at the age of 7 weeks in two experimental groups, of which one group was subsequently maintained on captopril (2 g l(-1))-containing drinking water, and at 10 and 13 weeks in two further groups. The fifth group provided age-matched controls. All groups (each n = 4 animals) were scanned consistently at 16 weeks, in parallel with timings used in earlier studies that employed this experimental model. Cine magnetic resonance (MR) image acquisition provided transverse sections through both ventricles at twelve time points covering systole and most of diastole. These yielded reconstructions of cardiac anatomy used to derive critical functional indices and their dependence upon time following the triggering electrocardiographic R waves. The left and right ventricular end-diastolic (EDV), end-systolic (ESV) and stroke volumes (SV), and ejection fractions (EF) calculated from each, control and experimental, group showed matching values. This confirmed a necessary condition requiring balanced right and left ventricular outputs and further suggested that STZ-induced diabetes produced physiological changes in both ventricles. Absolute left and right ventricular SVs were significantly altered in all diabetic animals; EDVs and EFs significantly altered in animals diabetic from 7 and 10 but not 13 weeks. When normalized to body weight, left and right ventricular SVs had significantly altered in animals diabetic from 7 and 10 weeks but not 13 weeks. Normalized left ventricular EDVs were also significantly altered in animals diabetic from 7 and 10 weeks. However, normalized right ventricular EDVs were significantly altered only in animals made diabetic from 7 weeks. Diabetic hearts showed major kinetic changes in left and right ventricular contraction (ejection) and relaxation (filling). Both the initial rates of volume change (dV/dt) in both ventricles and the plots of dV/dt values through the cardiac cycle demonstrated more gradual developments of tension during systole and relaxation during diastole. Estimates of the derived left ventricular performance parameters of cardiac output, cardiac power output and stroke work in control animals were comparable with human values when normalized to both body (or cardiac) weight and heart rate. All deteriorated with diabetes. Comparisons of experimental groups diabetic from 7 weeks demonstrated that captopril treatment relieved the alterations in critical volumes, dependence of SV upon EDV, kinetics of systolic contraction and diastolic relaxation and in the derived indicators of ventricular performance. This study represents the first demonstration using non-invasive MRI of early, chronic changes in diastolic filling and systolic ejection in both the left and the right ventricles and of their amelioration by ACE inhibition following STZ-induction of diabetes in intact experimental animals.
采用非侵入性磁共振成像(MRI)技术,对不同年龄雄性Wistar大鼠实验性链脲佐菌素(STZ)诱导糖尿病后左右心室心动周期的变化进行表征。同时,首次评估了血管紧张素转换酶(ACE)抑制剂卡托普利对这些慢性生理变化的影响。在两个实验组中,于7周龄时诱导糖尿病,其中一组随后饮用含卡托普利(2 g l(-1))的饮用水;另外两组分别在10周龄和13周龄时诱导糖尿病。第五组为年龄匹配的对照组。所有组(每组n = 4只动物)在16周时进行一致的扫描,扫描时间与早期采用该实验模型的研究一致。电影磁共振(MR)图像采集在十二个时间点提供了穿过两个心室的横截面,涵盖收缩期和大部分舒张期。这些图像重建了心脏解剖结构,用于推导关键功能指标及其对触发心电图R波后时间的依赖性。从每个对照组和实验组计算得到的左心室和右心室舒张末期容积(EDV)、收缩末期容积(ESV)、每搏输出量(SV)和射血分数(EF)显示出匹配值。这证实了左右心室输出平衡这一必要条件,并进一步表明STZ诱导的糖尿病在两个心室中都产生了生理变化。所有糖尿病动物的绝对左心室和右心室SV均有显著改变;7周和10周患糖尿病的动物EDV和EF有显著改变,但13周患糖尿病的动物没有。当按体重进行归一化时,7周和10周患糖尿病的动物左心室和右心室SV有显著改变,但13周患糖尿病的动物没有。7周和10周患糖尿病的动物归一化左心室EDV也有显著改变。然而,仅7周患糖尿病的动物归一化右心室EDV有显著改变。糖尿病心脏在左右心室收缩(射血)和舒张(充盈)方面表现出主要的动力学变化。两个心室的容积变化初始速率(dV/dt)以及整个心动周期的dV/dt值曲线均显示,收缩期张力发展和舒张期松弛过程更为平缓。将对照组动物的左心室心输出量、心脏功率输出和每搏功等性能参数按体重(或心脏重量)和心率进行归一化后,与人类值相当。糖尿病会使所有这些参数恶化。对7周患糖尿病的实验组进行比较表明,卡托普利治疗缓解了关键容积的改变、SV对EDV的依赖性、收缩期收缩和舒张期松弛的动力学以及心室性能的推导指标的改变。本研究首次使用非侵入性MRI证明了在完整实验动物中,STZ诱导糖尿病后左右心室舒张期充盈和收缩期射血的早期慢性变化,以及ACE抑制对这些变化的改善作用。