Endothelial dysfunction and impaired lymphatic drainage of the heart in the pathogenesis of cardiovascular complications in diabetes

Aim. To study the role of activation of lipid peroxidation and endothelial dysfunction in disorders of lymphatic coagulation and lymphatic drainage of the heart in streptozotocin-induced diabetes mellitus.

Methods. The experiments were performed on 25 rabbits. To simulate diabetes mellitus, animals were injected intraperitoneally with streptozotocin at a dose of 50 mg/kg. Indicators of lipid peroxidation, coagulation, and endothelial dysfunction were examined in lymph obtained by draining the thoracic lymphatic duct. We also examined the state of lymphatic drainage of tissues at the level of the thoracic lymphatic duct and at the level of the heart, before and after inducing diabetes.

Results. On the 5th day after inducing diabetes mellitus, the concentration of diene conjugates in lymph exceeded the initial level by 66.6% (p <0.001), and the concentration of malondialdehyde increased by more than 2.6 times (p <0.001); 30 min later these indicators of diene conjugates and malondialdehyde exceeded the initial values by 3.2 and 2.2 times, respectively (p <0.001), and the concentration of reduced glutathione decreased by 73.8% (p <0.001). At the same time, the indicators of lymph coagulation, activated partial thromboplastin time and thrombin time, were shortened by 42.2 and 32.9%, respectively (p <0.01). The rate of lymphatic drainage from the thoracic duct decreased by 81.8% (p <0.01). Such dynamics persisted throughout the experiment. The duration of the removal of a lymphotropic dye from the heart at stage I was increased on the 30th and 60th days of the study by 28.1% (p <0.05) and 57.9% (p <0.001), respectively. At stage II, this indicator decreased, starting from the 2nd month of the experiment it exceeded the initial level by 22.2% (p <0.05), and subsequently by 32.7% (p ≤0.001)

Conclusion. The activation of lipid peroxidation and intravascular coagulation of lymph, followed by inhibition of lymphatic drainage of tissues at the level of the thoracic lymphatic duct, especially the heart, creates favourable conditions for the accumulation of toxic products of impaired metabolism in the myocardium, contributing to the development of cardiovascular complications.