Quantitative ultrastructural analysis of rat cardiomyocytes after a prolonged stay in the mountains

Abstract

Disturbances of intracellular regeneration in cardiomyocytes (CMC) are demonstrated in rats kept for a prolonged period in the mountains. These disturbances cause focal destruction and lysis of organelles. The spatial intracellular reorganization of CMC under these conditions is characterized by an increased volume and surface density of myofibrils and decreased volume density of mitochondria, agranular sarcoplasmic reticulum, and T-system. Key Words: cardiomyocytes; ultrastructure; intracellular reorganization; high altitudes; stereologyLiving at high altitudes causes cardiac hypertrophy (predominantly of the right ventricle) in all mammalian species [1][2][3]10]. Such alterations in cardiac structure and function are considered to be adaptive and evolutionary, having developed in response to a rise of the blood pressure in the pulmonary circulation [5,9]. Different types of myocardial reorganization have been observed after different periods of hypobaric hypoxia. After a short-term hypobaric hypoxia, hypertrophy of cardiomyocytes is accompanied by a corresponding increase in the capacity of the microcirculatory bed, the density of capillaries in this case either increasing or remaining unchanged [6,11,12]. The imbalance between the increase in the size of CMC and capillaries is manifested in decreased volume and surface-volume ratios of capillaries to CMC [4]. Changes in the intracellular organization of CMC under different regimes of hypobaric hypoxia have been less studied, which hampers the development of prognostic criteria for the morphofunctional state of the myocardium under these conditions.After a short-term hypobaric hypoxia an increase in the mass of myofibrils [10,13,14] predominates, i.e., the type of structural changes characteristic of hypertrophied cardiac myocytes. The nature and direction of intracellular organization of CMC caused by a long-term hypobaric hypoxia have not been investigated; they were thus the topic of the present study. MATERIALS AND METHODSMale Wistar rats were used. They were kept at an altitude of 3200 m above sea level (Tyan-Shan' Mountains, Tuya-Ashu pass) [4,5] at room temperature on the standard diet and water ad libitum. Intracellular reorganization of cardiomyocytes was studied after a 5-or 10-month stay in the mountains (18 and 10 rats, respectively). Male Wistar rats of the same age kept in the valley were used as the control.For the electron microscopy studies specimens of the left-ventricle myocardium were fixed in 4% paraformaldehyde, postfixed in 1% osmium tetroxide, dehydrated, and embedded in araldite. Ultrathin