Water status and LPO in rat tissues during massive blood loss and irradiation with He-Ne laser.

We revealed a relationship between water balance and LPO in the myocardium, liver, and blood plasma during massive blood loss and irradiation with He-Ne laser. Low-intensity laser irradiation of the plasma inhibits LPO and normalizes water balance in rat tissues during massive blood loss.

[Effect of perftoran on cerebral blood flow in the reperfusion period after global transient brain ischemia]. / Vliianie perftorana na tserebral'nyi krovotok v reperfuzionnyi period posle global'noi prekhodiashchei ishemii golovnogo mozga.

It was established, while modeling the global transient cerebral ischemia in experiments with 51 anesthetized nonlinear white rats (weight 300-330 g), that a preliminary administration of perftoran in the discussed pathology does not only improve the reperfusion process in the brain but also levels the deficits of crystalloid solutions used as blood substitutes (by the example of physiological solution). Therefore, the drug has a cytoprotective action on the vascular-system endothelium. A direct admixture of perftoran to the autoblood introduced after global transient cerebral ischemia improves essentially the reperfusion-period course in the brain versus the combination of physiological solution and autoblood.

[Various forms of water in the rat myocardium and liver during blood loss and the early postresuscitation period]. / Zakonomernosti izmeneniia razlichnykh form vody v miokarde i pecheni krys pri krovopotere i v rannem postreanimatsionnom periode.

Different forms of water content were studied in myocardium and liver of male rats at 2-h hypotension and during the early postreanimation period. The phenomenon of redistribution of free and bound water was found. Comparison of water balance during the postreanimation period in the myocardium and liver revealed that normalization of different forms of water occured in myocardium. In hepatocytes oedema remained over the whole period studied.

[Acute and massive hemorrhage: mechanisms of compensation and damage]. / Ostraia massivnaia krovopoteria: mekhanizmy kompensatsii i povrezhdeniia.

To evaluate the body's compensatory reserves, experiments were made on anesthetized (with heparine) mongrel dogs of both sexes weighing 8-25 kg. The experiments have indicated that early monitoring of physiological parameters (external respiration, cardiovascular performance, hemostasis, red blood cell morphometry) in the first 5-10 minutes of acute massive hemorrhage is of high informative value. The generalization of vasoconstriction resulting in higher overall blood volume, the maintenance of venous return, tachypnea, active spontaneous hemodilution, and increased heart rate are the leading mechanisms of perfusion pressure maintenance in early acute hemorrhage. The severity of acute damage to the membranes of red blood cells and endotheliocytes and hence changes occurring in the suspension structure of blood, which drastically impairs its rheological parameters and fluidity, can play the key role in the pathogenesis of decompensatory cardiovascular and visceral functions in prolonged arterial hypotension. The findings open up new possibilities for early evaluation and prediction of the ensurina course of delayed massive hemorrhage.

Morphologic changes of red blood cells during hemorrhagic shock replicate changes of aging.

Blood loss leads to the reduction in vitality of red blood cells (RBCs). However, the changes in morphology at different stages of hemorrhagic shock have not been studied. Thus, the aim of this study was to identify and quantitate the sequence of morphological changes in RBCs during hemorrhage. This study was performed on 15 adult inbred dogs. Blood samples were taken before hemorrhage, when the mean arterial pressure reached 40 mm Hg (initial stage of shock), and at a mean arterial pressure level of 20 mm Hg (decompensated stage of shock). The volume of blood removed averaged 33.6+/-8.9 and 55.1+/-6.9 mL/kg, respectively. Evaluation of RBC morphology was performed by computerized light microscopic morphometry and scanning electron microscopy. At the early stage of hemorrhage the number of "young-appearing" RBCs with large visible surface areas (41-50 microm2) increased from 17.7%+/-3.1% to 26.6%+/-3.5% (P < 0.05). Concomitantly, the number of "old-appearing" RBCs with small visible surface area (20-30 microm2) significantly decreased from 5.3%+/-2.7% to 2.7%+/-2.3% (P < 0.01). At the stage of decompensated blood loss, the opposite phenomenon was observed. The number of "old-appearing" RBCs increased to 8.2%+/-1.1% (P < 0.01), whereas the number of "young-appearing" RBCs decreased to 12.3%+/-4.2% (P< 0.01). The changes in visible surface area of RBCs was accompanied by significant alterations in their shape. The percentage of abnormal shaped RBCs increased from 8.9%+/-1.1% before the hemorrhage to 36.4%+/-5.8% at the stage of decompensated hemorragic shock (P < 0.01). Thus, during the late decompensated stage of hemorrhagic shock, RBCs assume shape and surface area changes that are similar to those seen in aging. These changes in RBC size and shape may be due to the effects of shock-induced oxidative stress.

[Effect of laser exposure on hemostatic parameters in the preagonal and post-resuscitation period]. / Deistvie lazernogo izlucheniia na parmetry gemostaza v preagonal'nom i postreanimatsionnom periode.

Effects of intravascular low-intensive laser exposure of the blood on the hemostasis during acute blood loss and the early postresuscitation period after 4-min clinical death were studied on narcotized dogs (8-17 kg) of both sexes with different initial levels of heparin. During the preagonal period laser exposure caused hypercoagulation in animals with initial heparin content below 60 micrograms/ml. This acceleration of blood clotting prevented a drop in the activity of antithrombin III and hypercoagulation by the third hour of postresuscitation period. In animals with initial heparin content more than 60 micrograms/ml laser exposure caused hypocoagulation in the presence of reduced activity of antithrombin III by the third hour of the resuscitation period.

[The biogenic amine content of rat tissues in the postresuscitation period following hemorrhagic shock and the effect of the preparation semax]. / Soderzhanie biogennykh aminov v tkaniakh krys v postreanimatsionnom periode posle gemorragicheskogo shoka i vliianie preparata semaks.

LPO products were measured in plasma and biogenic amines (serotonin, adrenalin, noradrenalin) in tissues of rats in different periods after hemorrhagic shock provoked by taking blood and maintenance of arterial pressure at the level of 40 mm Hg for 1 hour. Resuscitation was conducted by administration of autoblood. It was found that splenic serotonin levels decreased on experiment day 7 and went up on day 28. On late experiment stages noradrenalin levels in the adrenals were high. Early after resuscitation the trend was noted to higher LPO products concentration in plasma and serotonin in the brain stem. Intravenous injection of semax prevented serotonin fall in the spleen on experiment day 7. It is suggested that biogenic amines, especially serotonin system, are involved in mechanisms of postresuscitation disorders, in cerebral defects in particular, through prolongation of secondary hypoxia early after hemorrhagic shock and activation of hypothalamo-hypophyso-adrenal system late after the shock.

[Hemocoagulation while dying of blood loss and restoration to life after clinical death]. / Gemokoaguliatsionnye parametry pri umiranii ot korovopoteri i ozhivlenii posle klinicheskio smerti.

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.

[DNA-endonucleolysis in cell nuclei of brain and liver in patients dying from hemorrhage and after resuscitation: general patterns and differences]. / DNK-endonukleoliz v kletochnykh iadrakh mozga i pecheni pri urmiranii ot korovopoteri i posle reanimatsii: obshchie zakonomernosti i razlichiia.

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.

[Low-energy laser irradiation of blood as a method of prevention of blood circulation decompensation in hemorrhagic shock]. / Nizkoénergeticheskoe lazernoe obluchenie krovi kak sposob profilaktiki dekompensatsii krovoobrashcheniia pri gemorragicheskom shoke.

Effect of low-intensity laser exposure of the blood on the central hemodynamics, oxygen transporting function of the blood, oxygen balance of the organism, and surface configuration of erythrocyte membranes was studied in dogs exposed to 2-h arterial hypotension (arterial pressure 40 mm Hg). Blood exposure was started from the tenth min of hypotension and went on for 45 min (group 2) or 120 min (group 3); group 1 was control. The best results were attained after 45-min laser exposure. A longer exposure creates prerequisites for complications, such as dysadaptation of the vascular tone and delayed decrease of hemoglobin concentration.

[Effect of verapamil on the activity of Ca2+-, Mg2+-dependent endonucleases in hypothalamic cell nuclei in long-term hypovolemic shock]. / Vliianie verapamila na aktivnost' Ca2+-, Mg+-zavisimykh éndonukleas v kletochnykh iadrakh gipotalamusa pri dlitel'nom gipovolemicheskom shoke.

Experiments on anesthetized non-inbred 8-17 kg b.w.dogs have demonstrated that cerebral ischemia consequent to 4-hour hypovolemic shock activates Ca(2+)-, Mg(2+)-dependent endonucleases in cell nuclei of the hypothalamus. Intravenous injection of calcium channels blocker verapamil (Orion) in a dose 0.1 mg/kg 30 min before blood loss prevents activation of the above endonucleases and makes it possible to avoid internucleosome fragmentation of genome DNA.

[The effect of low-intensity laser radiation on the parameters of the blood anticoagulation system in the early postresuscitation period]. / Vliianie nizkointensivnogo lazernogo izlucheniia na parametry protivosvertyvaiushchei sistemy krovi v rannem postreanimatsionnom periode.

The effect of low-intensive laser exposure at a wavelength of 634 nm and power 1 mWt at the tip of the light-guide on the blood anticoagulative system was studied in mongrel narcotized dogs of both sexes weighing 8 to 16 kg during the postresuscitation period after 4-min clinical death from massive blood loss. The anticoagulative system in the blood plasma was depleted during the reanimation period (the activities of plasmin and fibrinogen-heparin complexes and the level of heparin dropped). Intravascular laser exposure of the blood (for 30 min during blood loss after drop of the mean arterial pressure to 40 mm Hg and at the beginning of the second hour of the postreanimation period) boosted the activities of plasmin and fibrinogen-heparin complexes but failed to increase the level of heparin in the postreanimation period.

[Changes in the functional status of the left-ventricular myocardium during dying and in the early postresuscitation period]. / Izmeneniia funktsional'nogo sostoianiia levogo zheludochka pri umiranii i v rannii postreanimatsionnyi period.

Experiments on dogs have shown that left-ventricular contractility reduces and the processes of contraction and relaxation are discoordinated during the first minutes of dying from acute blood loss with the mean arterial pressure of 40 mm Hg. During the postreanimation period following a ten-min clinical death spontaneous respiration is resumed late (after 15.1 +/- 3.2 min), as are the corneal reflexes (after 46.1 +/- 8.5 min). If there are no changes in left-ventricular contractility in the course of dying, vital functions of the organism and neurological reflexes recover sooner (respiration after 6.1 +/- 2.0 min and corneal reflexes after 32.6 +/- 4.1 min). A relationship has been revealed between the severity of the postreanimation period and the degree of reduction of left-ventricular myocardial contractility during hypoperfusion (1 to 6 hrs after reanimation): the contractility index in animals with late neurologic recovery was lower than in those with a relatively early neurologic recovery.

[The neurochemical, molecular and ultrastructural mechanisms of the formation of latent postresuscitation encephalopathy]. / Neirokhimicheskie, molekuliarnye i ul'trastrukturnye mekhanizmy formirovaniia skrytoi postreanimatsionnoi éntsefalopatii.

The content of total RNA and DNA, activity of Ca2+, Mg(2+)-dependent DNA endonuclease, and ultrastructural changes in nerve tissue cells were examined in the brain cortex of narcotized dogs 1 to 3 months after a 4-hour hemorrhagic shock (arterial pressure 40 mm Hg). A new variant of reconstruction of cell membranes and organelles formed by them was revealed, developing in the brain neurons in the course of adaptation during the first-third months of the postshock period. Evidently, the molecular base of development of an atypical variant of cell structure rearrangement in the remote period after shock is the internucleosomal fragmentation of a part of the DNA of nerve cells resultant from DNA endonucleolysis and subsequent information disintegration of a cell as a system. This distorts the process of biosynthesis of supramolecular ensembles, specifically, of nerve cell biomembranes.

[Significance of DNA endonucleases in the pathogenesis of ischemic lesion of the brain during massive hemorrhage]. / Znachenie DNK-éndonukleoliza v patogeneze ishemicheskogo porazheniia mozga pri massivnoi krovopotere.

Experiments on dogs exposed to hemorrhagic shock demonstrated a direct relationship between the duration of arterial hypertension and activities of Ca(2+)-Mg(2+)-dependent DNA-endonucleases in the cellular nuclei of the cerebral cortex. Appreciable differences in the kinetics of accumulation of acid-soluble products of DNA chromatin in the cellular nuclei of the cerebral cortex were detected: chromatin DNA degradation was the most rapid in the nervous tissue of dogs exposed to 6 h hemorrhagic shock. Verapamil, a Ca blocker, injected to animals 30 min before massive hemorrhage in a dose of 0.1 mg/kg, reliably reduced the activities of Ca(2+)--Mg(2+)-dependent endonucleases of the cellular nuclei of the cerebral cortex by the 4th h of hemorrhagic shock. The detected physicochemical changes in the chromatin DNA of the cerebral cortex cellular nuclei and a progressive increase of activities of Ca(2+)--Mg(2+)-dependent endonucleases during a prolonged hemorrhagic shock are by their nature close to the phenomenon of genomic programmed cellular death.

[Changes in the oxygen balance of the body in the acute period of hemorrhagic shock and after resuscitation under the effect of intravascular helium-neon laser irradiation of the blood]. / Izmeneniia kislorodnogo balansa organizma v ostrom periode gemorragicheskogo shoka i posle reanimatsii pod vliianiem vnutrisosudistogo gelii-neonovogo lazernogo oblucheniia krovi.

The effect of intravascular laser irradiation of the blood (ILIB) on the oxygen budget of the body and blood acid-base balance in the acute period of hemorrhagic shock and after resuscitation was studied in experiments on dogs. Duration of hypotension was 2 h. Laser therapy was started from the 5th-8th min of hypotension and lasted for 45 min; it was performed with a He-Ne laser (ALOK-1, 1 mWt power at the tip of the light guide, wavelength 633 nm) introduced in the right jugular vein. Exposure to ILIB in the acute period of hemorrhagic shock was conducive to creation of favorable conditions for realization of the compensatory mechanisms aimed at improvement of circulation and gas exchange in the lungs, at provision of delivery of oxygen to tissues and its utilization, and, hence, promoted the survival of animals by triggering the regulatory mechanisms of redistribution of the regional bloodflow, improvement of tissue perfusion, and possibly, of oxyhemoglobin dissociation processes in red cells.

[Molecular and cellular mechanisms of ischemic damage of the brain in hemorrhagic shock]. / Molekuliarnye i kletochnye mekhanizmy ishemicheskogo povrezhdeniia mozga pri gemorragicheskom shoke.

General lightening of caryoplasma, the appearance of destructive areas in which electron-optic density was undetectable, ruptures in chromatin chains, changes in the nature of structural organization of euchromatic areas at the expense of density redistribution have been found in the nuclei of brain cortex oligodendrogliocytes and astrocytes by electron microscopy of caryoplasma of the nuclei from light neurons during experiments on anesthetized adult mongrel dogs weighing 9 to 26 kg recovered after a 4-hour hemorrhagic shock (BP 40 mm Hg). The nuclei of dark neurons and oligodendrogliocytes had matrix structure similar to control. The nuclei of astrocytes had marked matrix lightening with the formation of large zones in which electron-optic density was undetectable. It is evident that the degree of chromatin destruction in different neurons was not identical in hemorrhagic shock and depended on the functional neuronal activity. It has been established that there is a significant increase in the activity of nuclear Ca2+, Mg(2+)-depended endonucleases associated with chromatin and irreversibly cleaving ds- and ss-chromatin DNA chains. We believe that an increase in Ca2+, Mg(2+)-depended DNA-endonuclease activity should be considered an important pathogenetic factor in destructive processes that take place in the nuclei of brain cortex neurons in severe hemorrhagic shock.