Quantitative ultrastructural characteristics of the mitochondria network of ventricular muscle cells during prenatal ontogeny under the chronic hypoxia
DOI:
https://doi.org/10.14739/2310-1237.2013.3.22352Keywords:
rats, myocardium, cardiogenesis, mitochondria, hypoxiaAbstract
Background.
According to world literature there are 40-70% of newborns with injury of the cardiovascular system due to abnormally low levels of oxygen in utero. During cardiac development and differentiation of myocytes the structure of individual mitochondria and the cellular mitochondrial network is quite variable. However, hypoxia-induced reorganization of mitochondrial metabolism leads to changes in the volume density, numerical density, size of the organelles, transformation of the outer and especially the inner mitochondrial membrane, ultrastructure of the cristae and as a result a different level of intensity of ATP synthesis and implementation of normal contractile function of the heart.
Objective is a quantitative ultrastructural analysis of the formation and reactions of the mitochondria network in rat ventricular muscle cells during prenatal ontogeny under the chronic hypoxia in the experiment.
Methods. White rats were used as a material. Intrauterine hypoxia was modelled by intraperitoneal injection of sodium nitrite from 10th to 21st day of pregnancy. Embryonic hearts on the 14th, 16th, 18th and 20th days of prenatal ontogenesis were investigated by the transmission electron microscopy. Volume density, numerical density and surface density of the inner membrane of mitochondria were estimated. The Paired Student’s t-test was applied.
Results. Under the hypoxic conditions during rat prenatal ontogenesis the most significant processes of mitochondria destruction take place in the subsarcolemmal and intermyofibrillar regions of ventricle cardiomyocytes. Reducing the volume density of mitochondria in the sarcoplasm of the contractile cardiomyocytes under conditions of hypoxic injury may be associated with the group of factors. First, intrauterine hypoxia leads to a slowdown in the perinatal shift from lactate and glucose to free fatty acids as primary fuel sources and the result was reduction of growth and mitochondrial oxidative phosphorylation, which can be enhanced by high dependence on glycolysis as an energy source in hypoxic myocardium. Second, prenatal hypoxia generates a significant delay in incorporating mechanisms involved in mitochondrial growth and imbalances in plastic processes leading to these reactions. The observed inverse trend between changes in the volume density of mitochondria, the numerical density and between the surface density of the inner membrane of mitochondria may be an unique alternative adaptive mechanism in hypoxic rat fetal heart, this requires further study.
Conclusion. Chronic intrauterine hypoxia leads to delayed rate of growth and development of the mitochondria heterogeneity of the ventricular muscle cells in the prenatal stages of cardiogenesis, which is accompanied by a significant delay of volume density and numerical density of mitochondria from the 16th day of development in the right ventricle and from the 18th day in the left ventricle comparing with the norm.
Changes of the parameters are different in the heart parts and depend on the layer of myocardium. On the 20th day the volume density and numerical density were significantly reduced comparing with the control group and constitute in the right ventricle -42,1% (p <0,05) and -40,9% (p <0,05) in the intramural zone and less significant in the left ventricle - 33,7% (p <0,05) and -29,9% (p <0,05) of the same zone of the myocardium. Under the influence of hypoxia the surface density of the inner membrane of mitochondria showed the opposite trend and significantly increases from the 18th day of early cardiogenesis in both ventricles compared to the norm.
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