Magnetic resonance imaging studies of cardiac changes in diabetic and hypertensive rats

Magnetic resonance imaging (MRI) was applied as a non-invasive technique to characterize, for the first time, the structural and functional changes in the left and right ventricles following induction of diabetes in streptozotocin-treated rats. The effects of the angiotensin-converting enzyme inhibitor captopril upon such changes were also investigated. Finally, the MRI methods were also used to characterize the corresponding right ventricular changes in the spontaneously hypertensive rats (SHR), also for the first time. The MRI studies of the diabetic heart were performed on male Wistar rats subdivided into four groups, each containing four animals. Diabetes was induced in three groups by single intraperitoneal streptozotocin injections at the age of 7, 10 and 13 weeks respectively, leaving an untreated control group. A further group was maintained on captopril-containing drinking water immediately after the induction of diabetes at the age of 7 weeks. All animals were scanned at the age of 16 weeks, thus providing groups that had been diabetic for 9, 6, and 3 weeks respectively that were all age-matched to the single control group. The cine magnetic resonance imaging protocol imaged both ventricles at twelve time-points through the cardiac cycle covering systole and most of diastole. The subsequent quantitative analysis derived the anatomical and functional indices of left and right ventricular myocardial volume, end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV), and ejection fraction (EF). They also characterized the kinetics of left and right ventricular contraction and relaxation through the initial rates of left and right ventricular ejection and filling and by plotting such rates, dV/dt, through the studied twelve timepoints through the cardiac cycle. The MRI measurements yielded consistent myocardial volumes in both ventricles through all twelve time-points and in all the five experimental groups. Furthermore, the myocardial densities of both ventricles deduced from the post-mortem weights and myocardial volumes as measured by MRI closely agreed between groups and with previous reports. The subsequent analysis demonstrated significant relative left and right ventricular hypertrophy as reflected in the myocardial volume normalized to body weight, associated with diastolic and systolic functional abnormalities that developed between 3 and 6 weeks of diabetes. There was a further deterioration at 9 weeks. Such deteriorations were greatest between 3 and 6 weeks of diabetes in the left ventricle and between 6 and 9 weeks of diabetes in the right ventricle. Finally, captopril treatment commenced immediately after the induction of diabetes prevented the development of the relative hypertrophy in both ventricles and markedly relieved the diastolic and systolic abnormalities. MRI has been recently used to characterize the anatomical and physiological parameters describing the left ventricle in the SHR rats but has not been applied to the right ventricle. This, together with recent histological evidence of pulmonary hypertension in SHR rats prompted an MRI study of the right ventricle of the SHR rats. The experiments compared eight SHR and eight normotensive Wistar-Kyoto control rats (WKY). Each group of eight rats was subdivided into equal two-age matched categories of 8 and 12 weeks. As before, the right ventricle of all the experimental rats was imaged at twelve time-points through the cardiac cycle covering the whole of systole and most of diastole and the analysis derived the right ventricular myocardial volume, EDV, ESV, SV, and EF as well as right ventricular volume changes with time and dV/dt values. The analysis demonstrated for the first time hypertrophy of the right ventricles associated with diastolic and systolic dysfunction in the SHR rats. These studies thus use MRI for the first time successfully to demonstrate directly the development of cardiac changes in the left and right ventricles in an animal model of diabetes and right ventricular changes in an animal model of hypertension.Digitisation of this thesis was sponsored by Arcadia Fund, a charitable fund of Lisbet Rausing and Peter Baldwi