[Improvement of myocardial remodelling and functioning in patients undergoing surgical treatment of chronic cardiac insufficiency by two-staged elevation of the immunoregulatory reserve of autological bone marrow cells and their intramyocardial application].

The aim of the investigation was to study a possibility to improve left ventricular (LV) volume and function remodelling in patients with chronic cardiac insufficiency (CCI) by means oftwo-stage bone marrow cell (BMC) activation: first in vivo and then ex vivo within the process of their cultivation. Two groups of CCI patients were recruited. Group 1 (controls) consisted of 50 patients undergoing conventional aorto-coronary bypass surgery (ACBS). Group 2 consisted of 57 patients injected with 200 million autological mononuclear BMC intramyocardially during ACBS. In Group 2 patients, the severity of immune dysregulation was assessed initially using blood leukocyte stimulation index (SI) values. Sixteen patients with SI >1 and moderate immunographic alterations were considered to have a favorable prognosis for BMC treatment; 41 subjects with SI <1 and pronounced immunographic abnormalities were regarded as having an unfavorable prognosis for BMC application. Twenty-two patients with SI <1 were administered a preliminary immunocorrective course (in vivo BMC activation). Mononuclear BMC obtained from 38 patients with SI >1 and 19 patients with SI <1 were cultured for 5 to 7 days (ex vivo BMC activation). Positive changes in BMC phenotypical pattern were observed only in patients with SI >1: CD3, CD4, CD8, CD25, and some other measurements increased. Significant positive effects on LV function parameters and Duke Activity Status Index (DASI) values were revealed in patients with SI >1 six months after BMC administration. In vivo immunocorrection in combination with subsequent ex vivo BMC activation (n=38) promoted significant improvements in LV volume characteristics 6 months after ACBS vs. the controls (ACBS without BMC, n=50). In conclusion, to make the administration of autological BMC in CCI patients effective, two-staged BMC activation should be performed: in vivo activation with immunocorrectors should be followed by ex vivo activation of cultured cells.