Key result
Long-term nalbuphine induces progressive myocardial microstructural damage and mitochondrial alterations in rats.
Why the study?
The study aimed to determine the features of the structure and biochemical parameters of cardiac muscle and blood under normal conditions and long-term opioid exposure in rats.
Long-term nalbuphine administration in rats induces significant ultrastructural damage to cardiomyocytes, including mitochondrial alterations and microvascular occlusion.
This scientific work presents theoretical conclusions and a new solution to the scientific task, which consists in determining the features of the structure and some biochemical parameters of the blood and organs of the cardiac muscle of a white rat under normal conditions and under long-term opioid exposure. The experiment was conducted on 53 white male rats with a body weight of 130-210 g. Animals were divided into 3 groups – experimental (30 animals), control (18 animals) and 5 animals to check the standards before the experiment. The use of optical and electron microscopy confirmed that the heart muscle of the white rat is composed of muscle fibers that branch and intertwine to form a specific mesh. Myofibrils, on the other hand, consist of a chain of sarcomeres separated by Z-lines, each containing 2-3 mitochondria of all 3 types. There are 3 types of mitochondria in the sarcoplasm of cardiomyocytes: 1 type of elongated mitochondria, which have a relatively large volume and a well-developed complex of cristae; mitochondria of the 2nd type have a rounded shape, which, compared to the mitochondria of the I type, have a smaller volume and a smaller number of cristae; 3 type of mitochondria of very small volume, but with a large number of crystals. Cardiomyocytes are connected to each other with the help of intercalated disks. The gaps between cardiomyocytes are filled with loose connective tissue with nerves and components of the microcirculatory bed represented by arterioles, precapillary arterioles, capillaries of the somatic, unfenestrated type, postcapillary venules and venules. The first signs of damage to the microstructure of the myocardium are visible 7 days after the administration of nalbuphine to white rats. During the next 35 days of the experiment, the pathological changes manifested by the violation of the well-defined structure of the heart muscle, fragmentation of muscle fibers, pronounced perivascular edema and fibrosis increase. Small-caliber vessels are markedly hyperemic with “sludge syndrome” in the lumen of microvessels. Administration of nalbuphine causes well-defined changes in the ultrastructure of the rat heart. First of all, it is manifested in a change in the shape, size of mitochondria, structure and number of cristae. In addition, there were changes in the nuclei of parenchymal cells – they acquired a non-uniform shape due to chromatin fragmentation. This may indicate the beginning of apoptosis. In addition, there are changes in the structure of microvascular blood flow – changes in the endothelial coating of microvessels of the heart, occlusion of coronary vessels, aggregation of erythrocytes and platelets on the luminal surface of endotheliocytes.
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Pokotylo et al. (2022) studied this question. Nalbuphine vs. Control group was evaluated on Changes in the microstructure of the myocardium and mitochondrial apparatus. Administration of nalbuphine in white rats caused progressive damage to the myocardium microstructure and changes in the shape, size, and cristae of mitochondria over 42 days.
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