Lipid metabolism and lymph coagulability in the postresuscitation period

The values of lipid metabolism and lymph coagulation in the restoration period after resuscitation were studied in experiments on rabbits. A clear correlation between the values was revealed. Increase of concentration of total lipids and of lipid fractions was accompanied by increase of the lymph coagulation potential, which led to disturbed tissue drainage of lymph and was one of the important causes of the development of postresuscitation complications. The elaboration of pathogenetic therapy for regulation of lipid metabolism and lymph coagulation in the postresuscitation period is necessary.     

DNA-endonucleolysis in cell nuclei of brain and liver in patients dying from hemorrhage and after resuscitation: general patterns and differences]

Specific features of Ca2+, Mg2+ dependent DNA endonucleolysis in the nuclei of the cerebral cortex, hypothalamus and liver were investigated in mongrel anesthetized male and female dogs. The endonucleolysis was studied in different periods of long-term arterial hypotension and in postresuscitation period, with strain pUC 19 plasmids as substrate for determination of nuclear endonuclease activity. It was established that nuclear DNA-endonucleases coupled with chromatin activated earlier in brain cortical and hepatic neurons than in the hypothalamus. Changes in activity of the enzymes directly correlated with duration of CNS ischemia. Active endonucleolysis occurred in cerebral and hepatic nuclei even 3 months after the blood loss and resuscitation. Postresuscitation changes in Ca2+ and Mg2+ dependent endonucleases in cortical nuclei are phasic while in the liver their activity for three months did not differ much from that in the end of hypotension. The activity of nuclear endonucleases in the hypothalamus returned to normal after beginning of resuscitation and did not change later. The data obtained evidence for active involvement of apoptosis mechanisms in brain and liver cell degeneration in massive blood loss and in postresuscitation period including a late one.     

Ionic composition of arterial and mixed venous plasma in the unanesthetized dog.

The use of permanent catheters in the aorta and pulmonary artery permitted the establishment of normal values for hemoglobin concentration in blood and -or pH, PCO2, osmolality, and protein and electrolyte concentrations in the plasma of arterial and venous samples from unanesthetized, undisturbed dogs, and the comparison of the ionic composition of simultaneously taken arterial and venous samples. Arterial samples yielded the following mean values: CHb, 143 g liter-1; pHP, 7.427; PCO2, 32.5 mmHg; CPosmol, 295 mmol kg-1; CPpr, 73.1 g liter-1, CPNa+, 148.0; CPK+, 3.9; CPCa2+, 2.38; CPMg2+, 0.85; CPCl-, 116.0; CPHCO3-, 21.1; CPlact-, 1.4; CPphosph, 1.21; net cation equivalency, 16.4; and anion gap, 1.03 mmol liter-1 in eight male mongrel dogs with seven or eight samplings from each dog. The anion gap in arterial and venous plasma was small, indicating that the contribution of sulfate and organic acids to the ionic composition of dog plasma is quantitatively unimportant. In simultaneously taken arterial and venous samples the following significant arteriovenous differences were found: HP, +0.038; PCO2, -5.6 mmHg; CPosmol, -1.8 mmol kg-1; protein, -0.8 g liter-1; CPNa+, -1.0; CPK+, -0.1; CPCl-, +1.3; and CPHCO3-, -1.7 mmol liter-1. These differences are explained on the basis of the changes that occur in blood upon the addition of CO2 and the ensuing chloride and water shifts.     

Recirculation of lymphocyte subsets (CD5+, CD4+, CD8+, SBU-T19+ and B cells) through gut and peripheral lymph nodes

The surface phenotypes (CD5+, CD4+, CD8+, SBU-T19+, MHC class II+, T80+ and sIg+) of lymphocytes in blood, and in prescapular and ileocaecal efferent lymph of sheep, have been determined. The similarity in the distribution of lymphocyte subsets in both lymph compartments indicated that the non-random migration of lymphocyte populations to peripheral lymph nodes and gut could not be due to preferential migration of a particular lymphocyte subset such as CD4+ or CD8+ cells to one tissue. Marked differences in the percentage of lymphocyte subsets between blood and efferent lymph suggested that some lymphocyte subsets leave the blood with differing efficiencies and that differential extraction of lymphocyte subsets from blood by a lymph node may be due to subset-specific lymphocyte-endothelial interactions.     

Acid-base balance of the cerebrospinal fluid in the postresuscitation period

In experiments on dogs whose circulation was stopped for 10 min by electric shock the acid-base balance of the cerebrospinal fluid (CSF) and blood was studied in the postresuscitation period. Although uncompensated systemic acidosis continued for 1 h of the postresuscitation period, acidosis of the CSF was compensated much sooner and was maintained for 6 h at the initial level. Despite the high lactate concentration for 3 h of the postresuscitation period, the bicarbonate concentration during this period remained close to its initial value.Laboratory of Experimental Physiology of Resuscitation, Academy of Medical Sciences of the USSR. (Presented by Academician of the Academy of Medical Sciences of the USSR V. A. Negovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 11, pp. 1303–1305, November, 1976.     

Structural basis of impairment of the external respiratory function in the post-resuscitation period

External enhancement of free-radical processes followed by considerable tissue accumulation of toxic lipid peroxidation products in an early postresuscitation period is the main pathochemical mechanism which causes lung air-blood barrier disturbance. The basis of animal respiratory insufficiency morphogenesis after clinical death is ventilation failure (dis- and atelectasis), circulation disorder (edema, hemorrhage) being secondary. However, morphological examination of lungs of animals after four-minutes clinical death from an acute blood loss and resuscitation showed that it is the severity of circulation disorders that determines the animals condition in the postresuscitation period.     

Effect of reduced concentration of various electrolytes on the myocardium during reperfusion

Reperfusion of isolated rat heart after cardioplegia with a solution containing 20% less Na+, K+, Ca2+, Mg2+, and H+ (the blood plasma electrolyte concentration of patients changes just within these ranges during operations on the open heart) leads to severe cardiac insufficiency. The direct cause of the disturbed contractile function of the heart in this case is reduced osmolality of the perfusion solution and/or simultaneous decrease of Na+ and H+ concentration.     

Role of disorders of metabolism in rat myocardium and endotoxemia in the pathogenesis of post-resuscitation cardiodepression

The model of 4-min clinical death due to acute blood loss was used to study cardiac contractility, myocardial metabolism and causes of endotoxemia in early postresuscitation period. The investigations were made on the whole body, isolated, isovolemically contracting heart and isolated papillary muscle. A marked reduction in functional myocardial reserves, maximal within the first 24 hours of postresuscitation, with dominant defects in relaxation was seen. Pathogenetic factors responsible for cardiodepression are the following: hypoxia, impairment of bioenergetics, hyperactivation of lipid peroxidation, acidosis, membrane destruction, endotoxemia.     

Changes in serum lysozyme activity in terminal states caused by blood loss

The dynamics of the serum lysozyme activity was investigated in dogs after surviving clinical death for a period of 1 min as a result of blood loss giving rise to hypovolemic hypotension lasting 2 h. A progressive increase in the serum lysozyme activity in the course of hypotension and during the first 30 min of the postresuscitation period was found. Increased lysozyme activity of the serum was detected during the 4 days after resuscitation. The importance of the serum lysozyme activity as an indicator of hypoxic damage to the internal organs in terminal states is discussed.     

Pulmonary microcirculatory bed and alveolar tissue in the postresuscitation period

Structural changes in alveolar lung tissue microcirculatory bed and circulatory disturbances (edema, hemorrhage, thrombosis) were studied in postresuscitation period after experimental clinical death following acute hemorrhage and mechanical asphyxia. Circulatory disturbances proved essential in the pathogenesis of postresuscitation respiratory insufficiency, follow a stepwise pattern and in early postresuscitation (up to 7 days) are pathogenetically associated with coagulopathic changes. There are periods of primary, marked and delayed disturbances, and the period of reparative changes which may cover up to 30 days since resuscitation. It is emphasized that the pattern and the degree of lung tissue damage in the postresuscitation are largely determined by circulatory disturbances.     

Changes of electrolyte metabolism, acid-base equilibrium, and coagulation of blood and lymph in acute myocardial infarction

Experiments were conducted on dogs to study disorders of the acid-base equilibrium (ABE), electrolyte metabolism, and the blood and lymph coagulation potential in different periods after the development of acute myocardial infarction (AMI). It was found that AMI modelling in dogs leads to marked changes of the values of the electrolyte metabolism, ABE, and coagulation of blood and lymph. Earlier and deeper disorders of many values occur in the lymph. Comparison of the data obtained shows on the main that the shifts in the blood and lymph are of a similar direction. The differences in the changes in both humoral media are quantitative in character.     

Hemocoagulation while dying of blood loss and restoration to life after clinical death]

Hemostatic system function was studied in dogs dying of acute blood loss and restoring to life after 4-min clinical death. Phasic changes in hemostatic system of two and three types occurred in the blood loss and reanimation, respectively. Dogs with favorable postresuscitation period exhibited hypercoagulation when dying, hypocoagulation 1 hour after reanimation and normal coagulation 3-6 hours after clinical death.     

The mechanisms of the impact of preliminary immunization with staphylococcus anatoxin on postresuscitation pathology of the myocardium

Chronic experiments lasting for 5 weeks were carried out in 40 nonpedigree mature dogs. It has been detected that preliminary immunization with staphylococcus anatoxin potentiates the compensation mechanisms in the course of postresuscitation period, stimulates cell proliferation by increasing cardiac output that is an adaptive reaction of the cardiovascular system in postresuscitation period and provides optimal metabolism of the organism.     

CD4+ lymphocytes are extracted from blood by peripheral lymph nodes at different rates from other T cell subsets and B cells

The circulation of lymphocyte subsets through prescapular lymph nodes in sheep has been quantified using a panel of monoclonal antibodies against sheep lymphocyte surface antigens. Differences in the extraction of lymphocyte subsets from blood by the lymph node were found with CD4+ lymphocytes being extracted at a faster rate (1/2) than CD8+, SBU-T19+, major histocompatibility complex class II+ and B cells (1/4 to 1/5). In order to accommodate existing data on organ-specific adhesion molecules, one subset specific and one tissue specific, expressed on vascular endothelium could act jointly to regulate the migration of recirculating lymphocytes.     

The vacuolated glycogen-laden leukemic lymphocytes of a T-cell lymphoproliferative disorder

In this report, we present a case of peripheral T-cell leukemia/lymphoma having mostly small- to medium-sized cells with abundant clear cytoplasmic vacuoles. The presentation at the time of diagnosis was one of leukemia/lymphoma. The phenotype of the leukemic cells of the peripheral blood was T1+, T11+, TQ1+, interleukin-2+, T3-, T4-, and T8-. The cells in the peripheral blood as well as those obtained from lymph node biopsy were strongly periodic acid-Schiff positive; the positivity was diastase sensitive. Electron microscopy confirmed the presence of glycogen in the cytoplasmic vacuoles. Serologic tests were negative for human T-cell lymphotropic virus type 1 antibody. The data presented in this article support the existence of a vacuolated variant of peripheral T-cell leukemia/lymphoma and further expand the morphological spectrum of T-cell lymphoproliferative disorders.     

T cell malignancy in Richter's syndrome presenting as hyper IgM. Induction and characterization of a novel CD3+, CD4-, CD8+ T cell subset from phytohemagglutinin-stimulated patient's CD3+, CD4+, CD8+ leukemic T cells

A patient is described, having Richter's syndrome and immunodeficiency with hyper IgM, who developed suppressor T cell lymphoma (CD3+, CD4-, CD8+) following untreated helper-suppressor T cell chronic lymphocytic leukemia (CD3+, CD4+, CD8+). The neoplastic T cells in both malignancies expressed interleukin (IL) 2 receptors but were deficient in typical CD2+ and CD5+ pan T antigens. Additionally, a large percentage of malignant lymph node T cells expressed HLA-DR+ activation antigens. In vitro immunoglobulin-production experiments demonstrated that the patient's leukemic blood T cells had an excess helper function for IgM synthesis but a suppressor function for IgG and IgA synthesis by normal B and T cells. The leukemic blood T cells demonstrated a poor response to phytohemagglutinin (PHA). A defect in IL 2 receptor expression was evident in PHA-stimulated leukemic blood T cells. Of interest was the observation that PHA stimulated the induction of a novel CD3+, CD4-, CD8+ T cell subset from patient's CD3+, CD4+, CD8+ leukemic blood T cells. These PHA-induced CD3+, CD4-, CD8+ T cell subsets produced an elevated proliferative response to PHA and concanavalin A, had a helper cell function for IgM synthesis and produced highly elevated amounts of IL 2.     

Changes in cerebellar purkinje cells during postresuscitation period: Morphometric and ultrastructural analysis

Morphometric and electron microscopic analysis of rat cerebellar Purkinje cells was carried out after external neurological recovery following 10-min systemic circulation arrest caused by clamping cardiac vascular bundle, in order to elucidate the mechanisms of delayed encephalopathies. The composition of Purkinje cell population notably changed during the postresuscitation period. Ultrastructural disorders in these neurons, persisted for 1 month after resuscitation. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 129, No. 1, pp. 103–108, January, 2000     

Left ventricular assist device support induces acute changes in myocardial electrolytes in heart failure

The regulation of myocardial electrolyte concentrations is critical to proper cardiac function. Myocardial ischemia is associated with deranged ion transport. Left ventricular assist device (LVAD) therapy improves myocyte bioenergetics in chronic heart failure (CHF), which may manifest as electrolyte alterations; however, rapid electrolyte shifts may place critically ill patients at risk for arrhythmias upon initiation of LVAD support. We examine the effect of incremental increases in LVAD support on acute changes in myocardial arteriovenous electrolytes in CHF. CHF was induced in sheep via coronary microembolization. Four months later, sheep underwent acute LVAD implantation. LVAD support was incrementally increased (0%, 25%, 50%, 75% support). Paired arterial and coronary sinus blood samples were obtained at each increment and analyzed for K+, Ca2+, and Na+ concentrations. Arteriovenous electrolyte concentrations (mmol/l) were inverted in CHF before LVAD support: K+ (-0.08), Ca2+ (-0.04), and Na+ (0.04). These imbalances were corrected within 20 minutes and with as little as 25% LVAD support: K+ (0.06), Ca2+ (0.012), and Na+ (-0.80). The arteriovenous differences further widened as LVAD support was increased. In conclusion, LVAD support in CHF induces acute alterations in myocardial electrolytes. Rapid shifts myocardial arteriovenous electrolyte balances during LVAD support may in part explain the incidence of post-LVAD arrhythmias observed clinically in humans.     

Chondriome ultrastructure of rat cardiomyocytes after apparent death and in the postresuscitation period

Twelve-minute blockade of blood circulation caused different changes in cardiomyocyte organelles, particularly in the mitochondria. The initial cardiomyocyte structure was restored within 3.5 h of the postresuscitation period. Ultrastructural changes in cardiomyocytes were observed again 1 month after resuscitation. They disappeared after 5 months. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 127, No. 1, pp. 95–100, January 1999     

Effects of presensitization and clinical death in the history on the dynamics of morphofunctional parallels of retinal and cerebral circulation]

A negative effect of preliminary sensibilization with a normal serum and clinical death (restoring to life according to V. A. Negovsky et al.) on cerebral blood supply and eye retina within 5 weeks of postresuscitation period was studied on dogs. Microcirculation disorders in the groups of sensibilized dogs were more prominent as compared to intact animals. The diameter changes of pial and retinal microvessels did not correlate, but qualitative alterations in retinal and cerebral microvessels were of the same type.