Experimentally induced intrauterine growth restriction in rabbits leads to differential remodelling of left versus right ventricular myocardial microstructure
Intrauterine growth restriction (IUGR) is associated with foetal cardiac remodelling and dysfunction together with increased risk of cardiovascular disease in adulthood. Experimental data concerning effects of IUGR on cardiomyocyte and microvascularization anatomy are inconsistent and it is unknown whether both ventricles are similarly susceptible to in utero undersupply. Foetal IUGR was induced in pregnant rabbits at 25 days of gestation by selective ligation of uteroplacental vessels. Foetal echocardiography showed systolic and diastolic dysfunction of both ventricles and body and heart weight were significantly reduced in response to IUGR. Design-based stereology revealed a decrease in cardiomyocyte number in both ventricles which was only in the left ventricle accompanied by a significantly higher cardiomyocyte mean volume. The proportion of mono- and bi-nucleated cardiomyocytes was unaltered between the groups indicating a similar maturation status. The number and length of cardiac capillaries in IUGR offspring was diminished in left but not in right ventricles. Foetal left and right ventricles are differently affected by placental insufficiency. While cardiomyocyte numbers are diminished in both ventricles, hypertrophic remodelling of cardiomyocytes and alterations in microvascularization is rather a left ventricular adaptation to IUGR. These unequal structural changes may be related to loading and developmental differences of the left and right ventricles.
KeywordsIUGR Cardiomyocyte number Microvascularization Ventricle-related
The authors wish to thank Susanne Kuhlmann and Christa Lichtenberg for expert technical assistance. This work was partially supported by the German Research Federation (DFG: REBIRTH Cluster of Excellence), Grants from Instituto de Salud Carlos III (Grants Number PI14/00226, PI15/00130 and INT16/00168), the Spanish Ministry of Economy and Competitiveness (Grant TIN2014-52923-R) and cofinanced by the Fondo Europeo de Desarrollo Regional de la Unión Europea “Una manera de hacer Europa” (FEDER), and AGAUR 2014 SGR Grant No. 928. The research leading to these results has received funding from Obra Social “la Caixa” Foundation and CEREBRA.
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