On the Occasion of the 100th Anniversary of V. A. Negovsky, Academician of the Russian Academy of Medical Sciences 

The paper deals with Academician V. A. Negovsky’s views of the significance of the central nervous system in the formation of postresuscitative pathology and with the development of this problem at the present time. It also gives Academician V. A. Negovsky’s statements on the most important matters of reanimatology. The authors present the current studies of V. A. Negovsky’s disciples, the researchers of the Institute founded by him, which deal with the regularities of and the mechanisms responsible for the development of posthypoxic encephalopathies. Under discussion are the problems associated with the time course of changes in the postresuscitative process, the impact of the duration of a terminal condition on brain damage, the significance of structure-function relationships, the selective vulnerability of different regions of the central nervous system, the role of the body’s individual and typological characteristics, as well as the methodological approaches to preventing and treating brain dysfunction. Key words: V. A. Negovsky, postresuscitative brain pathology, neuromorphology, regularities and mechanisms of the development of posthypoxic encephalopathies.

The paper covers the present ideas on the mechanisms of neuroprotection, indications for and contraindications to the clinical application of therapeutic hypothermia, possible complications, as well as the future areas of its use in intensive care. Key words: therapeutic hypothermia, ischemic-reperfusion lesion, critical conditions.

Objective: to develop approaches to therapy for postoperative peritonitis on the basis of an analysis of changes into some indices of the kallikrein-kinin system, such as the key plasma proteolytic system and the blood proteinase potential, in this complication. Subjects and methods. The indices of the blood kallikrein-kinin system (the activities of kallikrein, a1-pro-teinase inhibitor, o^-macroglobulin, total arginine-esterase activity, and the level of prekallikrein) were determined in 22 patients diagnosed, as having postoperative peritonitis, before and after transfusion of the fresh frozen plasma (FFP) prepared in the standard fashion and from the donors intranasally receiving biolan in a daily dose of 3 mg within three days before blood donation. Results. The studies have shown that the patients with postoperative peritonitis have a drastic imbalance in the proteinase inhibitor system with a preponderance of the former. After FFP transfusion, a^-proteinase inhibitor and a^-macroglobulin deficiencies persist in patients with peritonitis, which is prognostically poor. Transfusion of the FFP taken from the donors taking biolan results in mobilization of the body’s adaptive and compensatory capacities and causes an increase in the blood antiproteinase potential. Conclusion. Dynamic imbalance between proteinases and their inhibitors is of considerable importance in the pathogenesis of postoperative peritonitis; the estimation of the serum activities of a^-proteinase inhibitor and fl^-macroglobulin may be used as informative criteria for a systemic inflammatory reaction and therapeutic effectiveness. Key words: postoperative peritonitis, kallikrein-kinin system, proteinases, inhibitors, biolan.

Objective: to analyze on basis of an integrative (clinical, biochemical, and microbiological) assessment, the efficiency of using perfluorane as a complementary component to correct the intestinal status in patients with peritonitis. Subjects and methods. The study was conducted in 106 patients with generalized peritonitis, who were comparable in the severity and degree of endotoxicosis. According to the treatment option, three study groups were arbitrarily formed: Group 1 that comprised 42 patients receiving complex intensive therapy (a clinical comparison group) and two major groups who underwent enterosorption during intensive therapy: Group 2 that included 26 patients in whom perfluorane was additionally injected interintestinally and Group 3 that consisted of 30 patients who did not take perfluorane. To evaluate the effect of injected perfluorane, the parameters of endotoxicosis were studied on days 1, 3, and 5 and the nasointestinal discharge was examined using the conventional procedure on days 1, 2, 3, and 4. The clinical picture of the disease was monitored in the early postoperative period. Results. The study has demonstrated a reduction in the parameters of endotoxicosis, as well as earlier recovery of motor evacuatory function and stabilization of enteric microbiocenosis. Conclusion. The intraintestinal use of perfluorane favored a better postoperative period and reduced lengths of hospital stay. Key words: peritonitis, intestinal failure, enterosorption, perfluorane.

Objective: to study the diagnostic and prognostic values of the Mannheim peritoneal index (MPI) in the development of postoperative local and systemic complications in patients with peritonitis. Materials and methods. The case histories of 92 patients with generalized peritonitis of varying etiology (other than pancreatogenic one) were analyzed. The patients were retrospectively divided into 3 groups according to the outcomes and occurrence of postoperative local complications. The postoperative complications were classified by the procedure developed by A. L. Kostyuchenko et al. as local and systemic ones. When the patients had two signs or more of the systemic inflammatory response syndrome, they were stated to have systemic complications and to be diagnosed as having abdominal sepsis with the pattern of organ dysfunctions being described in accordance with the sepsis classification proposed by R. S. Bone et al. (1992). The number of organ dysfunctions was daily counted in each patient over time in the postoperative period. On the first postoperative day, MPI was calculated in scores for each patient; the mean MPI was estimated for all patient groups. The predictable mortality was calculated using the MPI plot. Results. All the patients with generalized peritonitis in the development of local postoperative complications were observed to have sepsis in the postoperative period, without developing local complication in 84.6% of the patients. A direct correlation was found between the MPI and the quantity of organ dysfunctions (r=0.6; p=0.001). In patients with local postoperative complications being developed, the MPI values were higher (p<0.05) than in those without them. The mortality rates that have been predicted by means of MPI (16.3%) and actual (15.2%) are actually in agreement. Conclusion. There is evidence for the diagnostic and prognostic values of MPI in the development of local and systemic postoperative complications in patients with peritonitis. MPI calculation from postoperative day 1 along with later dynamic estimation of the number of organ dysfunctions makes it to objectively assess not only prognosis, but also the pattern of postoperative peritonitis. The major advantage of MPI is the simplicity of calculation, which permits its use in clinics. Key words: peritonitis, prognosis, complications, sepsis, Mannheim peritoneal index.

Objective: to evaluate the efficiency of extracorporeal detoxification techniques in patients with abdominal sepsis. Subjects and methods. Three hundred and seventy-nine patients with acute generalized peritonitis were examined. Extracorporeal detoxifying techniques were used during conventional therapy in Group 1 (n=319); the other patients received only traditional therapy (a control group). The time course of changes in the parameters of toxemia, a hemostasiogram, and an immunogram were examined. Results. The study indicated significantly reduced endotoxemia and better blood aggregation resulting from the use of plasmapheresis, cryoplasmasorption, and plasmasorption, as well as stimulated immunity when the above techniques were combined with autoblood photomodification and extracorporeal immunopharmacotherapy in patients with abdominal sepsis. In severe abdominal sepsis and infectious-toxic shock, there was regression of multiple organ dysfunction and lower mortality when venovenous hemofiltration was applied. Conclusion. A differential approach to using active detoxifying techniques is needed, by taking into account the severity of the disease. Key words: abdominal sepsis, detoxifying techniques.

Objective: to study the role of oxidative stress in the development of cardiac structural and metabolic disorders in severe isolated brain injury (BI). Materials and methods. The impact of BI on the parameters of serum chemilu-minescence and the contractility of isolated rat hearts were studied in experiments on 66 outbred male albino rats, as described by E. T. Fallen et al. Lipid peroxidation processes were inhibited, by intraperitoneally injecting the antioxidant carnosine (100 mg/kg) 1 and 24 hours before or just after BI. Results. The rate of free radical processes rose an hour after severe isolated BI, which was associated with the indirect signs of cardiomyocitic membrane damages, depressed rat heart contractility, and their diminished resistance to hypoxia, reoxygenation, and exercise by high rhythm. Administration of carnosine to the animals favored the normalization of chemluminescent values with the high overall antioxidative capacity of serum. The effect of the agent depended on the time of its use and it was high when carnosine was injected 1 and 24 hours before injury. At the stage of reoxygenation after the hypoxic test, there was a significant increase in evolving pressure, the rate of left ventricular myocardial contraction and relaxation, and a reduction in AsAT activity in all coronary duct tests, as compared with the controls. A negative correlation was found between the burst amplitude and the myocardial relaxation rate in the animals receiving the agent. Conclusion. Improved cardiac contractility and increased capacities of the mechanisms responsible for Ca2+ transport due to the use of the antioxidant carnosine allow one to state that oxidative stress is one of the pathogenetic factors of cardiac depression in severe isolated BI. Key words: brain injury, heart, oxidative stress, carnosine.

Objective: to study the specific features of correction of central hemodynamics in hemorrhagic shock when various treatments are used. Materials and methods. Experiments were made on 38 mongrel dogs in 4 series of experiments: 1) 12 dogs under hemorrhagic shock (a control group); 2) 10 anemic animals receiving later infusion therapy; 3) 10 anemic dogs exposed to HBO (p02=300 kPa; a 60-min session); 4) 6 anemic dogs receiving complex treatment (HBO and infusion). Circulatory blood volume (CBV), cardiac index (CI), left ventricular stroke output index (LVSOI), heart rate, and blood pressure (BP) were determined in all the animals at the baseline, in 30-, 90-, and 150-min shock (controls) at 5 and 60 min after treatment. Results. In the posthemorrhagic period, all hemodynamic parameters were found to be decreased (p<0.01). After infusion therapy (Series 2), the central hemodynamic parameters with CBV normalization remained at the level of 30-min shock. After oxygenation (Series 3) and complex therapy (Series 4), CBV normalization was attended by the recovery of the study circulatory parameters. This was caused by lower hypoxia, activated myocardial metabolic processes, and stimulated adaptive hemodynamic reactions. Reducing the volume of an infusion mixture in Series 4 animals lowers a cardiac load, provides a positive effect in the treatment of terminal conditions. Conclusion. HBO used in the complex therapy of hemorrhagic shock is an important component ensuring the normalization of metabolic processes and hemodynamic homeostasis in posthemorrhagic states.

The paper shows how to solve the urgent problem of posthypoxic rat brain resistance to emotional stress. An hour hypovolemic hypotension (mean blood pressure 45 mm Hg) served as a model of a terminal condition. The integra-tive activity of the rat brain was evaluated by the elevated cross labyrinth test. Emotional stress was induced by confrontation between the falsely operated and antihypertensive rats within 30 postischemic days. Laser irradiation was carried out an hour after blood reinfusion. Laser irradiation used before emotional stress was shown to increase the resistance of the posthypoxic rat brain to emotional stress and to prevent the development of depression-like states in the late periods after resuscitation. Key words: blood loss, postresuscitative period, emotional stress, laser irradiation.

Academician of the USSR Academy of Medical Sciences V. A. Negovsky stated that there was an association of the pathogenesis of postresuscitative central nervous system (CNS) lesions with the individual typological characteristics. Therefore the objective of the investigation was to study the early brain structural and functional changes in resuscitated rats, which were related to the baseline type of behavior. The investigation was carried out on outbred albino male rats. Circulation was stopped under ether anesthesia for 10 minutes via intrathoracic ligation of the cardiac vascular fascicle. Before clinical death simulation, the animals were divided by the types of behavior according to their behavioral activity in the elevated cross labyrinth or open field test. Postresuscitatively, the rats were found to preserve their individual typological features of behavior. At the same time the animals with baseline various behavioral patterns showed great differences in becoming familiar with a new environment. The study of conditioned reflex activities suggested the predominant impact of postresuscitative cerebral changes on different mechanisms responsible for active avoidance conditioning in rats with baseline different behavioral types. Examination of the CA1 and CA4 pyramidal cell neuronal populations of the hippocampus indicated that in the elevated cross labyrinth test, the resuscitated animals with a high baseline behavioral activity had more pronounced neurodystrophic and degenerative changes in the study brain regions than the rats with a low activity. The findings not only have supported V. A. Negovsky’s ideas on the association of the pathogenesis of postresuscitative cerebral disorders with the individual typological characteristics of the CNS, but also revealed differences in the neuropathophysiological mechanisms of these disorders, and ascertained the structural features of postresuscitative cerebral lesions in the animals with baseline different type of behavior. Key words: ischemia, behavioral pattern, central nervous system, orientation-investigatory reaction, conditioned reflex, morphometry, neuronal populations.

To compare the clinical efficacy of antihypoxants having different mechanisms of action, the authors studied the results of treatment in 218 patients with severe acute poisoning by psychotropic drugs. The patients were divided into 1 control and 3 study groups in which antihypoxic agents, such as mexicor, cytoflavin, and cortexin, complemented a complex of therapeutic measures. Their use was ascertained to reduce the duration of coma, acute respiratory failure, the incidence of pneumonias, and the length of stay in an intensive care unit and a hospital and to substantially decrease mortality. The authors recognize it advisable to include antihypoxants into a complex of therapeutic measures for poisoning by psychotropic drugs. Key words: antihypoxants, acute intoxications, psychotropic agents.

Objective: to assess the diagnostic informative value of some neurovegetative parameters as criteria for evaluating the adequacy of cerebral circulatory recovery at the early stage of resuscitation. Materials and methods. Experiments were performed on 65 cats under anesthesia with nembutal, 45 mg/kg intraperitoneally. A model of 5-minute clinical death from prolonged blood loss (50 mm Hg, a Wiggers hemobarostat) was employed. Cerebral circulation (hydrogen clearance), cardiac output, and its distribution (thermodilution) were recorded. The autonomic indices, such as the Kerdo, Algover, Robinson, and Hilebrant ones, were calculated. An index of regulatory system tension was estimated (analysis of cardiac rhythm variability). Results. There was a close, direct correlation of postresuscitative changes in cerebral circulation with cardiac output and its redistribution. The phasic pattern of cerebral circulatory recovery is reflected by the time course of changes in the neurovegetative indices. In hyperperfusion, the baseline levels of the Kerdo and Algover indices were associated with the low values of the Robinson and Hilebrant indices and tension index. Conclusion. The neurovegetative parameters are of the most informative value in inadequate brain perfusion (considerable increases in the Kerdo and Algover indices and a reduction in the Robinson index). In brain blood overperfusion that is beyond the adaptive ranges, these parameters (apart from the tension index) do not change as those in the surviving animals. The practical use of the indices requires additional experimental and clinical studies. Key words: postresuscitative period, cerebral circulation, cardiac output distribution, neurovegetative indices.

Objective: to study central hemodynamics, the determinants of myocardial oxygen balance, and the parameters of oxygen transport in various activation of patients after surgery under extracorporeal circulation. Subjects and methods. Thirty-four patients aged 57.8±2.5 years who had coronary heart disease were divided into 2 groups: 1) those with late activation (artificial ventilation time 157±9 min) and 2) those with immediate activation (artificial ventilation time 33±6 min). Group 2 patients were, if required, given fentanyl, midazolam, or myorelaxants. Results. During activation, there were no intergroup differences in the mean levels of the major parameters of cardiac pump function, in the determinants of coronary blood flow (coronary perfusion gradients) and myocardial oxygen demand (the product of heart rate by systolic blood pressure), and in the parameters of oxygen transport, including arterial lactatemia. After tracheal extubation, the left ventricular pump coefficient was increased considerably (up to 3.8±0.2 and 4.4±0.2 gm/mm Hg/m2 in Groups 1 and 2, respectively; p<0.05) with minimum inotropic support (dopamine and/or dobutamine being used at 2.7±0.3 and 2.4±0.3 mg/kg/min, respectively). In both groups, there were no close correlations between the indices of oxygen delivery and consumption at all stages of the study, which was indicative of no transport-dependent oxygen uptake. Conclusion. When the early activation protocol was followed up, the maximum acceleration of early activation, including that using specific antagonists of anesthetics, has no negative impact on central hemodynamics, the determinants of myocardial oxygen balance and transport in patients operated on under extracorporeal circulation. Key words: early activation, surgery under extracorporeal circulation, tracheal extubation in the operating-room, central hemodynamics, oxygen transport.

Objective: to substantiate a need for early use of extracorporeal homeostatic correction techniques during cardiosurgical intensive care. Subjects and methods: A non-randomized study was conducted in 63 cardiosurgical patients with postoperatively evolving multiple organ dysfunction. The clinical efficiency and economic expediency of the early initiation of homeostatic correction were estimated by continuous low-flow venovenous hemofiltration on a Prisma apparatus. Results. The study has demonstrated the advantages of early (within the 36-hour postoperative period) initiation of a procedure by the time of organ dysfunction recovery, the length of stay on a resuscitation bed, and pharmacoeconomic indices. Conclusion. The early (at the stage of dysfunction, until hemostasis becomes stable and in the absence of drainage volume losses) initiation of hemofiltration in the development of multiple organ dysfunction after surgical interventions has been clinically and economically warranted. Key words: extracorporeal homeostatic correction, multiple organ dysfunction, cardiac surgery.

Pulmonary edema remains a topical problem of modern reanimatology. In clinical practice, there is a need for continuous monitoring of the content of extravascular water in the lung and the pulmonary vascular permeability index for the timely detection and treatment of pulmonary edema. This literature review considers the minor mechanisms of pulmonary extravas-cular water exchange in health and in different types of pulmonary edema (acute lung injury, pneumonia, sepsis, postoperative period, burns, injuries etc.), as well as the most accessible current (irradiation and dilution) studies permitting an estimate of the level of pulmonary extravascular water and the pulmonary vascular permeability index in clinical practice. Key words: pulmonary edema, acute lung injury, pulmonary extravascular water, pulmonary vascular permeability index.

In the past years, the interest of theorists and clinicians has steadily increased in the myocardially secreted hormones – natriuretic peptides. At the Congress of the European Society of Anesthesiology (Munich, 2007), B-type natriuretic peptides were included into the list of the parameters of perioperative laboratory monitoring that is expedient in the practice of anesthetists and resuscitation specialists. The literature review shows the history of discovery and identification of different types of natriuretic peptides and considers the matters of their biochemistry. It also details information on the synthesis, secretion, and clearance of these peptides, as well as their receptor apparatus in various organs and tissues. The physiology of the regulatory system is described, as applied to the cardiovascular, excretory, central nervous systems, and the neuroendocrine one. Special attention is given to the current publications on the control of B-type natriuretic peptides as biomarkers of cardiac dysfunction. The diagnostic and prognostic values of peptides are analyzed in chronic circulatory insufficiency, coronary heart disease, and other car-diological and non-cardiological diseases. The prognostic value of elevated B-type natriuretic peptide levels in cardiac surgery is separately considered. It is concluded that the changes in the level of B-type natriuretic peptides in different clinical situations are the subject of numerous researches mainly made in foreign countries. The bulk of these researches are devoted to the study of peptides in cardiology and other areas of therapy. Studies on the use of peptides in reanimatology are relatively few and their results are rather discordant. The foregoing opens up wide prospects for studying the use of B-type natriuretic peptides in Russian intensive care and anesthesiology. Key words: natriuretic peptides, brain nautriuretic peptides, NT-proBNP.