No abstract

The main objective of anesthesiologist is maintenance of patient''s homeostasis during surgery. Among all the physiological parameters, only arterial pressure has such significant amplitude of oscillations, still the association between postoperative complications and blood pressure fluctuations is often unobvious. Furthermore, blood pressure is a modifiable parameter and can be easily regulated by fluids, vasopressor and inotropic agents in most cases. Intraoperative decrease of blood pressure may occur due to the action of anesthetics, hypotensive drugs, nonphysiological positioning of the patient on the operating table, artificial ventilation, surgical procedures, cardiopulmonary bypass, hypovolemia, acid-base and electrolyte disorders, acute heart failure, arrhythmias, anaphylaxis and others factors. The lack of consensus about the definition of hypotension makes difficulties in evaluation of its effect on human organism. More than 140 different absolute and relative values are used as hypotension thresholds. Nevertheless, the data accumulated over the past few years lead us to the conclusion that intraoperative decrease of blood pressure is associated with the development of various nervous, cardiovascular and renal complications, what ultimately leads to increased morbidity and mortality. Severity of adverse effects is a function of range and duration of blood pressure fall. Every patient has an individual set of genetic, physiological and pathophysiological features that determine the optimal blood pressure level. Thus, another promising direction may be development of the strategy for individualized blood pressure management.

The success of cell therapy depends on an effective method of cell delivery and engraftment. The use of transgenic cells carrying a reporter system based on the luciferase gene allows to perform the quantitative evaluation of the transplantation efficiency in dynamics using biochemical methods. The purpose of this work was to monitor the persistence of rat cardiosphere-derived cells (CDC) after allogeneic transplantation into the periinfarction zone. Transplantation was performed by intramyocardial injection of a cell suspension in a culture medium or in platelet rich plasma (PRP). When injected into the myocardium PRP forms fibrin clots which serves as a matrix for the transplanted cells. The cells were modified by the luciferase enzyme gene by transduction with lentiviruses (CDC-Luc). The activity of luciferase was determined in protein extracts of the myocardium at different time points after the transplantation. It was shown that in the first hour after injections, CDC-Luc is quantitatively detected in the peri-infarction zone irrespective of the use of platelet gel or medium, and their amount does not decrease within 48 hours. During this period, we found a positive effect of the fibrin matrix on the cells - the luminescence of CDC-Luc protein extracts in the platelet gel composition was significantly higher. We suggested that the platelet gel promotes a more favorable microenvironment for CDC-Luc and facilitates the adaptation of cells after transplantation, what reflected in the recovery of the level of luciferase production in cells. Further, we found negative dynamics: CDC-Luc injected in the culture medium is retained in the myocardium for 5 days and on the seventh day their presence is not determined, CDC-Luc in the fibrin matrix is retained in the myocardium for 10 days after transplantation. Thus, despite the successful transplantation of CDC, the integration of cells into the myocardium does not occur. Nevertheless, the use of platelet gel prolongates the time of CDC persistence in the tissue and enhances of their paracrine effect. The use of fibrin matrix can be useful for long-lived cells, such as cardiomyocytes, in particular, to improve the efficiency of transplantation of the tissue engineering biological pacemaker. A luciferase reportering system can be effective for in vitro and in vivo monitoring of cell fate, both in biotechnological stages of cultivation and assembly of the tissue engineering biopee maker, and after myocardial transplantation. In the future, the developed methodological approach will be used to study of tissue-engineering biopacemakers in experimental animals.