[Experimental therapy of cardiac remodeling with quercetin-containing drugs].

It was shown that continuous beta-adrenergic hyperstimulation resulted in cardiac function disturbances and fibrosis of cardiac tissue. Treatment with quercetin-containing drugs, particularly, water-soluble corvitin and tableted quertin exerted favourable effect on cardiac hemodynamics, normalized systolic and diastolic function in cardiac remodeling, induced by sustained beta-adrenergic stimulation. It was estimated that conducted experimental therapy limited cardiac fibrosis area almost three-fold, that could be associated with first and foremost improved cardiac distensibility, characteristics of diastolic and also pump function in cardiac remodeling.

Proteasome inhibitors eliminate protective effect of postconditioning in cultured neonatal cardiomyocytes.

A role of proteasomal proteolysis in the pathogenesis of ischemia-reperfusion is being actively studied. To evaluate the participation of the proteasome in postconditioning phenomenon, we used primary culture of neonatal cardiomyocytes. 30 minutes of anoxia followed by 60 minutes of reoxygenation was undergone. Postconditioning was modeled by 3 cycles of 1-minute reoxygenation followed by 1-minute anoxia, respectively. Clasto-lactacystin b-lactone, a specific proteasome inhibitor, in the dose that does not cause cell death (2.5 mM) was added to the culture medium just before the cycles of postconditioning. Percentages of living, necrotic, and apoptotic cells were determined by staining with bisBenzimide and propidium iodide. Autophagy was demonstrated by staining vacuolar structures with monodansyl cadaverine. Proteasomal activity was determined by cleavage intensity of specific fluorogenic substrates. Trypsin-like, chymotrypsin-like and peptidyl-glutamyl peptide-hydrolyzing (PGPH) activities were decreased after anoxia. Reoxygenation led to an increase in trypsin-like and chymotrypsin-like activities comparing to anoxia, but these parameters never reached the control levels. PGPH activity was restored up to the initial level. Postconditioning increased numbers of living cells and decreased that of necrotic, apoptotic and autophagic cells. Paradoxically, it was established, that proteasome inhibitors prevented the necrotic and apoptotic cell death of cardiomyocytes in anoxia-reoxygenation, but in the same concentration abolished the effects of postconditioning. The data obtained permit to suppose that proteasome inhibitors can be used for pharmacological postconditioning.

Postconditioning prevents apoptotic necrotic and autophagic cardiomyocyte cell death in culture.

In the paper the data concerning the possibility of the reproduction of the postconditioning phenomena in the cardyomicyte culture are presented. Primary cultures of cardiomyocytes from neonatal rats underwent 30 minutes of anoxia followed by 60 minutes of reoxygenation. Three different models of postconditioning were used: 3 cycles of 1, 3, or 5 minutes of reoxygenation followed by 1, 3, or 5 minutes of anoxia, respectively. The percentage of living, necrotic, and apoptotic cells were determined by staining with Hoechst 33342 and propidium iodide. Autophagy was demonstrated by the staining of vacuolar structures in vivo by monodansyl cadaverine. After anoxia and reoxygenation the amount of living, necrotic and apoptotic cells were 79 +/- 1.5, 7.8 +/- 0.9 and 13 +/- 1.5 %, respectively (in unstimulated cell culture 90 +/- 0.8, 3.3 +/- 0.3, and 5.5 +/- 0.7, P < 0.0001 for all). Postconditioning with 1 min anoxia 3-fold increased the amount of living cells and decreased the number of necrotic and apoptotic cells (P = 0.002, P = 0.02 and P = 0.043 respectively). Postconditioning with cycles of 3 and 5 minutes had a gradually reduced effect compared to cycles of 1 minute. The percentage of autophagic cells in control cell culture was 4.3 +/- 0.3%. This number increased after anoxia-reoxygenation to 14 +/- 0.8%, and was reduced by postconditioning (P < 0.001). The data obtained indicate that postconditioning is one of the effective methods of cardioprotection and could effectively decrease the amount of cardiomyocytes with traits of programmed or non-programmed cell death.