Non‐invasive magnetic resonance imaging assessment of myocardial changes and the effects of angiotensin‐converting enzyme inhibition in diabetic rats

Abstract

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.

B-Type Natriuretic Peptide Prevents Acute Hypertrophic Responses in the Diabetic Rat Heart

“…Diabetes impairs this antihypertrophic mechanism and may also compromise the long-term benefits of ACE inhibition on heart size clinically (10) and in experimental animals (7)(8)(9). Other investigators report no loss of antihypertrophic ACE inhibitor efficacy in diabetes (27)(28)(29), but in those studies, the reduction in heart size was secondary to a lowering of blood pressure rather than to a direct antihypertrophic effect as described here. Moreover, in the present study, 8 weeks of streptozotocininduced diabetes per se increased a number of markers of cardiac hypertrophy, including LV protein synthesis and LV ANP and ␤-MHC mRNA expression.…”

Type 1 Diabetes-Induced Hyper-Responsiveness to 5-Hydroxytryptamine in Rat Pulmonary Arteries via Oxidative Stress and Induction of Cyclooxygenase-2

“…In a previous study, insulin resistance in ApoE(Ϫ/Ϫ) mice was associated with PAH (Hansmann et al, 2007). We found previously PA endothelial dysfunction, a characteristic feature of PAH, in rats with type 1 diabetes, and right ventricular hypertrophy was also reported in streptozotocin-treated rats (Al-Shafei et al, 2002;Lopez-Lopez et al, 2008). Herein, we show that rats treated with streptozotocin share a number of pulmonary vascular abnormalities with animal models and patients with PAH such as down-regulation of BMPR2, COX-2 induction, up-regulation of 5-HT 2A receptors, and vascular hyper-responsiveness to 5-HT in addition to those described previously such as endothelial dysfunction and pulmonary vascular oxidative stress.…”

“…dicating that a major component of this phenomenon is not related to acute release of endothelial vasoactive factors. However, differences tended to be smaller in endotheliumdenuded compared with intact vessels, suggesting that endothelial dysfunction (Al-Shafei et al, 2002;Lopez-Lopez et al, 2008) might also play a role. Moreover, it seems to be secondary to the high blood glucose rather than a direct effect of streptozotocin because it was reduced by cotreatment with insulin.…”

“…Right ventricular hypertrophy has also been found in this model (Al-Shafei et al, 2002). We hypothesized that type 1 diabetes could lead to the development of PAH.…”

Cardiac function and lipid distribution in rats fed a high-fat diet: in vivo magnetic resonance imaging and spectroscopy

“…Increased plasma insulin concentrations are correlated with increased left ventricular mass (39). Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have been used in studies of dietary effects on cardiac function (2,27). Recent advances in magnetic resonance (MR) technology for high magnetic field systems, including the use of phased array radiofrequency coils, motion compensation techniques, and optimal radiofrequency pulse sequences, now permit investigation of cardiac function and metabolism in greater detail (32).…”