Early and Late Postnatal Myocardial and Vascular Changes in a Protein Restriction Rat Model of Intrauterine Growth Restriction

Intrauterine growth restriction (IUGR) is a risk factor for cardiovascular disease in later life. Early structural and functional changes in the cardiovascular system after IUGR may contribute to its pathogenesis. We tested the hypothesis that IUGR leads to primary myocardial and vascular alterations before the onset of hypertension. A rat IUGR model of maternal protein restriction during gestation was used. Dams were fed low protein (LP; casein 8.4%) or isocaloric normal protein diet (NP; casein 17.2%). The offspring was reduced to six males per litter. Immunohistochemical and real-time PCR analyses were performed in myocardial and vascular tissue of neonates and animals at day 70 of life. In the aortas of newborn IUGR rats expression of connective tissue growth factor (CTGF) was induced 3.2-fold. At day 70 of life, the expression of collagen I was increased 5.6-fold in aortas of IUGR rats. In the hearts of neonate IUGR rats, cell proliferation was more prominent compared to controls. At day 70 the expression of osteopontin was induced 7.2-fold. A 3- to 7-fold increase in the expression of the profibrotic cytokines TGF-β and CTGF as well as of microfibrillar matrix molecules was observed. The myocardial expression and deposition of collagens was more prominent in IUGR animals compared to controls at day 70. In the low-protein diet model, IUGR leads to changes in the expression patterns of profibrotic genes and discrete structural abnormalities of vessels and hearts in adolescence, but, with the exception of CTGF, not as early as at the time of birth. Invasive and non-invasive blood pressure measurements confirmed that IUGR rats were normotensive at the time point investigated and that the changes observed occurred independently of an increased blood pressure. Hence, altered matrix composition of the vascular wall and the myocardium may predispose IUGR animals to cardiovascular disease later in life

Submillimeter diffusion tensor imaging and late gadolinium enhancement cardiovascular magnetic resonance of chronic myocardial infarction

BACKGROUND: Knowledge of the three-dimensional (3D) infarct structure and fiber orientation remodeling is essential for complete understanding of infarct pathophysiology and post-infarction electromechanical functioning of the heart. Accurate imaging of infarct microstructure necessitates imaging techniques that produce high image spatial resolution and high signal-to-noise ratio (SNR). The aim of this study is to provide detailed reconstruction of 3D chronic infarcts in order to characterize the infarct microstructural remodeling in porcine and human hearts. METHODS: We employed a customized diffusion tensor imaging (DTI) technique in conjunction with late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) on a 3T clinical scanner to image, at submillimeter resolution, myofiber orientation and scar structure in eight chronically infarcted porcine hearts ex vivo. Systematic quantification of local microstructure was performed and the chronic infarct remodeling was characterized at different levels of wall thickness and scar transmurality. Further, a human heart with myocardial infarction was imaged using the same DTI sequence. RESULTS: The SNR of non-diffusion-weighted images was >100 in the infarcted and control hearts. Mean diffusivity and fractional anisotropy (FA) demonstrated a 43% increase, and a 35% decrease respectively, inside the scar tissue. Despite this, the majority of the scar showed anisotropic structure with FA higher than an isotropic liquid. The analysis revealed that the primary eigenvector orientation at the infarcted wall on average followed the pattern of original fiber orientation (imbrication angle mean: 1.96 ± 11.03° vs. 0.84 ± 1.47°, p = 0.61, and inclination angle range: 111.0 ± 10.7° vs. 112.5 ± 6.8°, p = 0.61, infarcted/control wall), but at a higher transmural gradient of inclination angle that increased with scar transmurality (r = 0.36) and the inverse of wall thickness (r = 0.59). Further, the infarcted wall exhibited a significant increase in both the proportion of left-handed epicardial eigenvectors, and in the angle incoherency. The infarcted human heart demonstrated preservation of primary eigenvector orientation at the thinned region of infarct, consistent with the findings in the porcine hearts. CONCLUSIONS: The application of high-resolution DTI and LGE-CMR revealed the detailed organization of anisotropic infarct structure at a chronic state. This information enhances our understanding of chronic post-infarction remodeling in large animal and human hearts. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12968-016-0317-3) contains supplementary material, which is available to authorized users