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.     

The blood and lymph electrolyte composition in the postresuscitation period

The electrolyte composition (Na+, K+, Ca2+, Mg2+) of blood serum and lymph was studied in experiments on 17 mongrel dogs in the postresuscitation period after clinical death. The concentration of these electrolytes reduced in the postresuscitation period. Comparison of data obtained in study of blood and lymph showed the revealed changes to be of one trend. The above-said is evidence of the expediency of including in the complex of postresuscitation therapeutic and preventive measures means for normalizing the electrolyte composition of not only the blood but also the lymph.     

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.     

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.     

Development of postresuscitation morphological changes of hippocampal and cerebellar neurons: common regularities and specific features

A comparative morphometric study of postresuscitation changes in the neuronal populations of the pyramidal cells from hyppocampal sector CA1 and Purkinje cells of the lateral cerebellar region in the course of postresuscitation period after 12-minute cardiac arrest in rats has shown that the changes differ in severity and pattern. In the pyramidal cells there were reversible dystrophic alterations of the neurons. Purkinje cells showed death of some neurons, this process progressed in the course of postresuscitation period. A positive effect of the peptide kyotorphin on the brain condition after resuscitation was found but its efficacy in different neuronal populations varied.     

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.     

Ca<Superscript>2+</Superscript> Transport into Sarcoplasmic Reticulum and Immediate-Early Response Proteins in the Myocardium of Rats Resuscitated after Systemic Circulatory Arrest

Activity of antioxidant defense enzymes and content of stress protein HSP70 in the heart increased in passive and, to a lesser extent, in active rats on day 7 of the postresuscitation period after systemic circulatory arrest. The resistance of membrane structures in the heart to endogenous damaging factors in passive rats was lower than in active animals. The degree of compensation in active rats was much higher than in passive animals at these terms of the postresuscitation period. __________ Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 140, No. 7, pp. 52–56, July, 2005     

Postresuscitation Changes in Neuronal Hippocampal Populations in Rats with Different Learning Ability

The state of pyramidal cell populations in CA1 and CA4 hippocampal fields was studied in resuscitated and intact rats with different learning ability. Morphometry showed that postresuscitation damage to neurons was more pronounced in good learners compared to poor learners. Interferometry revealed higher protein content in neurons in poor learners compared to successfully trained rats. It was hypothesized that different neuronal resistance to ischemia in rats characterized by different learning ability is determined by some peculiarities in protein metabolism preexisting in intact animals and manifesting in the postresuscitation period.     

Survival of dogs in the recovery period after prolonged hypovolemic hypotension

The survival rate and completeness of neurological recovery of functions of the CNS in the postresuscitation period were investigated in dogs in relation to the duration of hypovolemic hypotension, the arterial pressure level, and subsequent transfusion therapy. Administration of dextran in the early recovery period after hypovolemic hypotension in animals for 4 h increased the number of surviving dogs and led to complete restoration of functions of the CNS.     

Structural basis of functional heart failure during the postresuscitation period

Light and electron microscopic study of the myocardium of dogs two weeks after clinical death caused by the loss of blood was carried out and showed that the structural bases of the myocardium contractile function insufficiency during the postresuscitation period included the damage of the contractile apparatus of cardiomyocytes (microlysis and fragmentation of myofibrils, deformation of Z-bands, relaxation of sacromeres) and marked lysis of the sacrotubular system leading to the violation of the excitation-contraction coupling. Cardiomyocyte damages are associated with changes in the microcirculatory channel causing the worsening of transcapillary exchange that provides the tissue homeostasis.     

Changes in some hemodynamic,endocrine, and metabolic indices in the early postresuscitation period

Changes in the systemic circulation, the blood flow in the kidney and limb, and certain endocrine and metabolic indices were studied in 24 dogs subjected to circulatory arrest of maximal severity for 17 min in the course of 9 h of the postresuscitation period. Relative compensation and normalization of certain functions and metabolic indices during the first hour after resuscitation were subsequently followed by a new wave of disorders which developed at different times, unequally, and gradually in the body as a whole and in individual peripheral tissues. Disturbances of the peripheral circulation and central hemodynamics were shown to be among the leading pathological manifestations of postresuscitation sickness.Research Laboratory of General Resuscitation, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR V. A. Negovskii.) Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 87, No. 1, pp. 3–6, January, 1979.     

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.     

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.     

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     

The postresuscitation changes in the permeability of the hemato-encephalic barrier and their possible pathogenetic significance

Experiments were conducted on rats with temporary (10-min) clamping of the thoracic vascular bundle and subsequent resuscitation to study the permeability of the blood-brain barrier (BBB) to plasma albumins and globulins and to blood plasma immunoglobulins in different stages of the postresuscitation period. Mild increase of BBB permeability was detected 3 minutes after the beginning of recirculation. Permeability increased markedly in 24 hours and continued growing by the 72nd hour. At a 1-3-hour interval in recirculation the BBB was closed. The obtained results disclose the mechanisms of the development of autoimmune cerebral disorders in an organism that experienced cardiac arrest and resuscitation.     

The status of the erythrocyte membranes and their functional properties in the postresuscitation period

It was found that the deformation properties and peroxidation resistance of erythrocytes deteriorate in the postresuscitation period. On the basis of increase of the level of lipoperoxidation products and reduction of the level of alpha-tocopherol and nonprotein sulfhydryl groups, the authors conclude that lipid peroxidation in the erythrocyte membranes is activated after resuscitation. Disorders of molecular interactions are confirmed by the kinetics of nystatin fluorescent probe insertion and revealed increased cholesterol level in the erythrocyte membranes. It is suggested that the increase of the cholesterol level occurring as a protective response to the activation of lipid peroxidation transforms into a pathological reaction causing disorders of the deformation properties and peroxide resistance, which accelerates considerably the natural death of the erythrocytes after resuscitation.     

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.     

Active and Passive Behavior of Animals during the Postresuscitation Period

Behavioral reactions (open-field test, elevated plus-maze, pain stress, and feeding behavior) were studied in various periods after clinical death caused by circulatory arrest for 10 or 15 min. We revealed two different phases of behavioral changes: active behavior directed at attaining a specific goal and passive behavior directed towards isolation of the organism from external signals and functional minimization. Active behavior determined by pathological excitation in the central nervous system increased the severity of structural damage to hippocampal CA1 neurons during the postresuscitation period. By contrast, passive behavior and minimization of functions preserved structural integrity in these neurons.     

Some aspects of ammonia formation in the brain of dying animals and during recovery after resuscitation

The dynamics of some indices of nitrogen metabolism in the brain was studied in dogs after lethal blood loss and in the postresuscitation period. The investigation showed that the main source of ammonia in the brain during the development of the organism and in the state of clinical death is glutamine. In the recovery period after resuscitation, however, glutamine becomes a remover of ammonia and the main source of ammonia becomes the labile amino groups of proteins.Department of Pathological Physiology, Erevan Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. A. Negovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 83, No. 6, pp. 686–688, June, 1977.