The inotropic response of the myocardium to extrasystolic treatment was studied on isolated perfused papillary muscles from rats with postinfarction cardiosclerosis. The development of postinfarction cardiosclerosis was accompanied by a decrease in myocardial excitability. The amplitude of extrasystolic contractions in the remodeled myocardium far surpassed the control. However, the amplitude of postextrasystolic contraction did not surpass that in normal contraction-relaxation cycle. Our results suggest that the ability of the sarcoplasmic reticulum in cardiomyocytes to accumulate Ca2+ is impaired during postinfarction remodeling.

We studied the presence of colony-forming cells in cell culture from rat heart 40 days after experimental myocardial infraction. The mean cellularity in this pathology was 12+/-8 cell/cm2, which is 20-fold lower than in intact myocardium. Transplantation of mesenchymal stem cells into the remodeling myocardium restored the pool of colony-forming cells. This effect depended on the state of transplanted cells. After transplantation of mesenchymal stem cells with low content of stress proteins, 6+/-2 colonies were detected, while after transplantation of cells with high content of hsp70 and hsp60 stress proteins (modified mesenchymal stem cells) 18+/-5 colonies were found, the mean cellularity of the corresponding cultured being 946+/-267 and 1926+/-123 cell/cm2. The positive effect of modified mesenchymal stem cells was observed on days 4 and 7 after transplantation. We conclude that postinfarction remodeling mobilized the total pool of regional stem cells; mesenchymal stem cells with high content of hsp70 and hsp60 demonstrated highest survival rate after intramyocardial transplantation.

We studied the effects of recombinant granulocytic CSF on heart remodeling in BALB/c mice after cryodestruction. Administration of granulocytic CSF was started 1 day after cryodestruction (subcutaneously, 10 μg/kg/day, for 4 days). As early as after the first injection, leukocytosis in the peripheral blood started to develop, leukocyte count peaked on days 4-6 and returned to normal on day 14. Treatment with granulocytic CSF significantly increased the content of progenitor cells in the bone marrow and led to rapid development of the inflammatory reaction and myocardium infiltration with mononuclear cells. Injections of granulocytic CSF did not reduce scar area, but provided significantly less pronounced heart hypertrophy, which attests to its better functional properties. By day 30 after cryodestruction, control animals and animals receiving granulocytic CSF exhibited similar morphological picture at the site of damage. Thus, our regimen of granulocytic CSF administration produced a mobilizing effect on bone marrow progenitor cells and postinfarction heart remodeling. Direct effects of granulocytic CSF on the heart have to be established for its use in the treatment of myocardial infarction.