A female patient T., 67 years, had a 30-year anamnesis of heart failure, HF (NYHA Functional Class III) with normal left ventricular ejection fraction and Stage II arterial hypertension. After thyroidectomy in 1987, the patient received L-thyroxin. The patient also received long-term standard antihypertensive therapy and HF treatment. Due to ineffective therapy and increased dyspnoea, radionuclide ventriculography was performed, suggesting restrictive cardiomyopathy. Intracoronary injection of autologous bone marrow stem cells was performed. Four months later, an improvement in clinical status (NYHA FC I) was associated with improved diastolic function at ventriculography. Immunological analysis confirmed a virus infection.

A female patient T., 67 years, had a 30-year anamnesis of heart failure, HF (NYHA Functional Class III) with normal left ventricular ejection fraction and Stage II arterial hypertension. After thyroidectomy in 1987, the patient received L-thyroxin. The patient also received long-term standard antihypertensive therapy and HF treatment. Due to ineffective therapy and increased dyspnoea, radionuclide ventriculography was performed, suggesting restrictive cardiomyopathy. Intracoronary injection of autologous bone marrow stem cells was performed. Four months later, an improvement in clinical status (NYHA FC I) was associated with improved diastolic function at ventriculography. Immunological analysis confirmed a virus infection.

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.

The authors suggest using chemiluminescent reaction of the patients' blood leukocytes including the stimulation index (SI) for prediction of the body resistance to stress damage (operative stress). It is shown that in chronic cardiac patients (n = 259) SI is initially subnormal. Some of the above patients had critically low SI ( > 0.6). Such patients developed severe immunodependent postoperative complications. To increase the patients' resistance to operative stress and to avoid postoperative complications it is recommended to conduct prophylactic immunocorrecting therapy under SI control.

Coronary artery bypass grafting (CABG) has been made in two groups of patients with chronic heart failure (CHF) with further estimation of the rate of postoperative organic dysfunctions and pyoseptic complications. In group 1 (n = 50) CABG was combined with intracoronary or intramyocardial injection of autologous precultivated for 7-8 days mononuclear cells of the bone marrow (1 x 10(9) cells). In group 2 (n = 479) the intraoperative injection of the above cells was not made. It was found that autologous cultivated mononuclear bone marrow cells prevent organic dysfunction and reduce frequency of infectious-septic complications especially in patients with preoperative focuses of chronic infections.

Chronic cardiac failure is accompanied with immune dysregulation which severity predetermines the absence of clinic efficiency of autologous bone marrow stem cells (BMSCs). The effect of two-staged activation of bone marrow stem cells (at first, in vivo, then ex vivo) on left ventricle function promotion in patients with chronic cardiac failure has been studied. Two groups of patients with chronic cardiac failure took part in the investigation. The 1st group patients (control, n=50) underwent cardiopulmonary bypass. To the patients of the 2nd group (n=57) 200 mln autologous mononuclear marrow stem cells were introduced intramyocardially during the cardiopulmonary bypass. In the 2nd group patients the original immune dysregulation severity was assessed by assaying the index of white blood cells stimulation (SI) with a chemoluminescent test. In 16 patients with SI>1 and a moderate alteration of immunoassayjavorable effect of BMSCs was predicted bone marrow stem cells were predicted to produce unfavorable clinic effect in 41 patients with Sl1 and n=19 with SI1. Controlled immunocorrection performed before derivation of BMSCs, in combination with their subsequent ex vivo activation promoted reliable improvement of functional characteristics of the left ventricle 6 months after cardiopulmonary bypass in comparison with the controls. For autologous bone marrow stem cells to be effective in patients with chronic cardiac failure two-staged activation of BMSCs should be performed: at first, in vivo with immunocorrectors, then ex vivo while culturing.

The authors analyze the pathogenetic significance of inflammation, immune activation, and apoptosis in the development of heart failure and the functional regeneration of left ventricular myocardium after treatment including autologic bone marrow cell transplantation. The paper shows that autologic bone marrow cell transplantation influences the same mechanisms that cause heart failure, namely inflammation, apoptosis, and neurohumoral mechanisms. Investigations have made it possible to formulate guidelines for the prediction and monitoring of the effects of treatment including autologic bone marrow cell transplantation in patients with heart failure.