Age-dependent idiosyncrasies of the action of L-arginine, inosine and meldonium combination on contractile function of isolated rat hearts during adequate coronary perfusion, at ischemia and reperfusion

The contractile function of the myocardium decreases with aging. This decrease is associated with weakening of nervous control and a disruption of local and humoral mechanisms regulating cardiac function. Hypoxia and myocardial ischemia, which develop with age, play an important role. Pathological processes in the heart derive from disturbances in the structure and function of cell membranes. Mush attention therefore has been given to the study of the influence of various cytoprotectors and metabolic drugs on myocardial function. Here we investigated action of the combined membrane protective drug Melarginine (L-arginine, inosine and meldonium) on the isolated heart of adult and old rats under different perfusion regimens. We measured, in the isolated Langendorff-perfused heart, the maximum pressure developed by the left ventricle of the isolated heart (Pmax), the rate of pressure development in the left ventricle and the rate of pressure decrease in the left ventricle of the isolated heart (+dP/dt and –dP/dt, respectively), as well as the heart rate (HR). In old rats, Melarginine reliably increased the contractile capacity of the myocardium under the influence of damaging factors such as ischemia and reperfusion. With adequate coronary perfusion, Melarginine did not significantly affect myocardial function in old animals. In adult rats, Melarginine also had a positive effect on the isolated heart contractile function, but its cardioprotective effect was significantly less pronounced than in old animals. Thus, the obtained results allow us to recommend the use of Melarginine in the complex therapy of cardiovascular diseases, especially in geriatric practice.