Behavioral reactions of rats in the early postresuscitation period after systemic circulatory arrest of different duration.

Rats were exposed to systemic circulatory arrest for 10, 12, and 15 min. During the first 10 days after resuscitation exploratory activity of animals depended on the duration of systemic circulatory arrest and was determined by two opposite factors: high reactivity of the central nervous system contributing to intensification of exploratory activity, and impaired general state of survivors (inhibition of animal behavior).

Parameters of stress response at various stages of postresuscitation period.

Transient circulatory arrest (10 min) was followed by changes in rat adrenals and thymus and a decrease in blood calcium and protein contents typical of stress response. Maintenance under unfavorable conditions for a long time also produced changes in stress-target organs accompanied by a considerable shift in functional state of the central nervous system manifested in enhanced behavioral response to exogenous stimulation.

[Effect of perftoran on post-resuscitation recovery of the central nervous system]. / Vliianie perftorana na postreanimatsionnoe vosstanovlenie tsentral'noi nervnoi sistemy.

The effect of perfluorane on survival and restorative process in the brain were studied in rats subjected to 12-min arrest of systemic circulation. Perfluorane in a single dose of 5-10 ml/kg was injected intraperitoneally 30 min after the beginning of reanimation. The drug did not affect the postreanimation death of animals and time course of neurologic deficiency disappearance. Perfluorane activated behavioral reactions and prevented development of dystrophic changes in the brain structures of rats highly sensitive to hypoxia.

Some reasons for modifications of rat's conditioned behavior after resuscitation.

In rats survived systemic circulatory arrest and resuscitation, pathological changes such as increased excitability of the central nervous system and decreased volume of simultaneously acquired information considerably modulate conditioned activity. The interaction between these factors facilitates learning after formation of targeted behavioral pattern.

[Post-resuscitation neurosomatic deviations and the feasibility of their correction with a drug of metabolic action]. / Postreanimatsionnye neirosomaticheskie otkloneniia i vozmozhnosti ikh korrektsii preparatom metabolicheskogo deistviia.

Circulation in white rat males was stopped for 10 minutes by ligation of the intrathoracic vascular bundle of the heart. Proxipin in a dose 10 or 20 mg/kg was injected i.p. after restoration of effective cardiac activity and the next 3 days. Proxipin improved resuscitation outcomes, relieved symptoms of CNS excitability 4-6 months after resuscitation, changed adaptation to stress agents, protected against risk-factors of atherogenesis. However, proxipin-induced inhibition of the motor activity suppressed the free-choice ability to find food.

[Effects of active behavior in the postresuscitation period on the functional and morphological characteristics of the brain]. / Vliianie aktivizatsii povedeniia v postreanimatsionnom periode na funktsional'nye i morfologicheskie kharakteristiki mozga.

Efficacy of prolonged (days 10-60 after resuscitation) regular activation of behavior by labyrinth training of 4-staged food search conditioned reflex is studied in rats subjected to 15-min circulation arrest. This training affected the function of the central nervous system, which manifested by decreased anxiety and a higher activity in the open field test. This functional exercise prevented fall-out of neurons in the fifth layer of hemispheres, of cerebellar Purkinje's cells, and of pyramidal neurons in hippocampal sector CA1. These results support the hypothesis proposed by A. M. Gurvich on the possibility of regulating the postresuscitation recovery of the central nervous system by neurophysiological treatment of the brain.

Prophylaxis of encephalopathies and risk factors of atherogenesis development in the postresuscitation period in rats by means of succinic acid.

The effect of oral administration of succinic acid was studied in 66 rats exposed to 10 min cardiac arrest with further resuscitation. A total of 30 mg/kg of the drug were administered daily for 5 days starting with day 3 up to day 7 after resuscitation. The experiments have revealed that treatment with succinic acid caused normalization of the orienting behavior in an 'open field' test, decrease of the intensity of response to electric shock, normalization of free radical formation in the brain and serum and reduced cerebral morphological changes. The succinic acid prevented the increase of cholesterol, triglyceride and low density lipoproteins in the blood. The data suggested that after additional trials the succinic acid could be used to prevent development of postresuscitation encephalopathies (3 months after reanimation).

[The effect of succinic acid on postresuscitation pathology of the CNS and of the body as a whole]. / Vliianie iantarnoi kisloty na postreanimatsionnuiu patologiiu TsNS i organizma v tselom.

The effect of oral succinic acid was studied in rats exposed to 10-min heart arrest followed by resuscitation. The drug was administered for 5 days in a dose of 30 mg/kg starting from day 3 up to day 7 after resuscitation. Succinic acid was found to normalize the orientation and exploration behavior of rats in the "open field" test, decreased the intensity of response to stress (electric shock), and normalized the radical formation in the brain tissue and blood serum, thus reducing the morphological changes in the brain. In addition, succinic acid prevented the development of risk factors of atherogenesis, namely, increase of the levels of blood cholesterol, triglycerides, and low and very low density lipoproteins. Further studies are needed to validate the addition of succinic acid to the armory of drugs preventing the development of postresuscitation encephalopathies in remote (3 months) periods.

[Effects of sodium succinate on functional, biochemical and morphological indicators of CNS repair in rats after 10-minute circulation arrest]. / Vliianie suktsinata natriia na funktsional'nye, biokhimicheskie i morfologicheskie pokazateli vosstanovleniia TsNS u krys posle 10-minutnoi ostanovki krovoobrashcheniia.

Therapeutic effect of sodium succinate on various functional, biochemical, and morphological parameters of CNS repair was studied in experiments on rats exposed to 10-min circulation arrest. The first series of experiments was devoted to studies of the effects of the drug, injected intraperitoneally directly after recovery of effective cardiac activity and during the subsequent 5 days in doses 20, 100, and 200 mg/kg, on the survival and recovery of the external neurologic status. The dose of 20 mg/kg proved to be the most effective. The second series of experiments was devoted to therapeutic effect of sodium succinate in the same dose injected from day 3 to day 7 after revival on the orientation and investigation behaviour in an "open field" test, on changes in radical formation in the blood serum and the brain, and on the cholesterol/lipid ratio in the brain, as well as on the morphologic changes in the cerebral hemispheres and the cerebellum. In contrast to untreated animals, the treated ones had a less intensive reaction in the "open field" test in response to acute stressor exposure, their cerebral and blood serum levels of free radical processes were reduced, the destruction of neuronal membranous elements was less intensive, as were dystrophic changes in the cerebral cortex and the cerebellum. The data permit a conclusion about antistressor and protective effect of sodium succinate in the postresuscitation period at the functional, biochemical, and morphological levels.

[Regional perfusion and oxygenation in the early resuscitation period following prolonged clinical death]. / Regionarnaia perfuziia i oksigenatsiia v rannem postreanimatsionnom periode posle dlitel'noi klinicheskoi smerti.

Cardiac output distribution and oxygen supply in the period starting from 15 min after resuscitation to 7 h were studied in 23 dogs exposed to 10 min clinical death caused by blood loss. The ratio of supra- to subdiaphragmatic bloodstream was virtually unchanged. Redistribution of the flow in favor of hind limb muscles was observed in the subdiaphragmatic region only between the 15th and 30th minutes. Reduction of oxygen transport during prolonged hypoperfusion (2-6 h) was associated with increased oxygen utilization in all areas which was expressed most of all in the supra-diaphragmatic region and in limb tissues and the least so in the splanchnic area, with oxygen consumption remaining at the initial level or surpassing it. A close relationship was revealed between oxygen transport and consumption in the supradiaphragmatic sector and posterior limb tissues combined with critical levels of pO2 and HbO2 in outflowing blood. Stably surviving animals differed from those dead in 1 sec by a lesser depression of the bloodstream and oxygen transport in the body on the whole and in the supradiaphragmatic region, a lesser oxygen consumption by the supradiaphragmatic region at the 15th-30th minutes, and a higher O2 consumption in 3-6 h under conditions of more marked spontaneous hypothermia.

[Role of initial hemodynamic status and rate of blood loss replacement in postresuscitation changes in blood circulation and animal mortality]. / Rol' iskhodnogo gemodinamicheskogo statusa i tempov vozmeshcheniia krovopoteri v postreanimatsionnykh izmeneniiakh krovoobrashcheniia i gibeli zhivotnykh.

In 43 experiments performed on narcotized dogs after 10 min clinical death induced by exsanguination, the peculiarities of postresuscitation changes in the blood circulation associated with the initial hemodynamic status, the rate of the blood loss replacements after restoration of cardiac activity, and the use of infusion therapy by albosorb (specifically processed albumin) were studied. The effect of the initial level of stroke index (SI) on the pronouncement of postresuscitation derangements in the central hemodynamics (CHD) and on the resuscitation outcome was determined. With the initial value of SI being mean, the maintenance of a moderate blood deficit (10 to 15 ml/kg) within the first hour of restoration was accompanied by an improvement in the survival rate of the animals as compared with a rapid and complete replacement of the blood. The infusion of albumin and creation of a moderate overtransfusion by the first hour post resuscitation removed the prognostic value of the initial SI.

[Post-resuscitation toxemia and possibilities of its correction by albosorb]. / Postreanimatsionnaia toksemiia i vozmozhnosti ee korrektsii al'bosorbom.

Albumin with enhanced sorption capacity (albosorb) was infused in animals after 10 min long clinical death caused by blood loss to correct endogenic intoxication. The albosorb infusion enhanced the blood plasma astringency both with respect to hydrophobic and hydrophilic molecules.

[Absorption and release of biogenic amines by the lung during the restorative period after hypovolemic hypotension]. / Pogloshchenie i vysvobozhdenie biogennykh aminov legkimi v vosstanovitel'nom periode posle gipovolemicheskoi gipotenzii.

The processes of serotonin and histamine absorption and release by the lungs were studied in dogs during 1 to 3.5 hour hypovolemic hypotension and during 24 hours after blood retains fusion. Absorption of biogenic amines by the lungs tended to increase in all the animals under hypovolemic hypotension. In the group of non-survivors the serotonin absorption by the lungs in the post-terminal period remained increased, while in the group of survivors it came down to normal soon, though the histamine release was increased. The above processes were aggravated in the group of animals whose lungs were affected by oleic acid. It resulted in the absorption of histamine instead of its release. The intensified absorption of biogenic amines by the lungs was accompanied by a quick fall in cardiac output, by the increase in resistance of systemic and pulmonary circulation.

[Participation of the lungs in the absorption and liberation of biogenic amines in the postresuscitation period]. / Uchastie legkikh v pogloshchenii i vysvobozhdenii biogennykh aminov v postreanimatsionnom periode.

After revival from a 10-minute clinical death caused by acute blood loss the transport of biogenic amines to the lungs in dogs did not increase for 3 hours. Their absorption by the lungs was replaced periodically by their liberation; both processes were intensified for serotonin but weakened for histamine. In 6-9 hours during the period of hypoperfusion and reduction of the transport of amines to the lungs the intensity of absorption and liberation of serotonin by the lungs were normalized, while these processes for histamine remained diminished. The content of biogenic amines in arterial blood reduced. Twenty-four hours later, under conditions of normalization of hemodynamics, the transport of histamine to the lungs and its concentration in blood were still reduced, while the transport and absorption of serotonin by the lungs, as well as its content in arterial blood, increased; this was attended by an increase in total pulmonary resistance and the development of moderate hypoxemia. Animals who died subsequently had a higher level of serotonin in arterial blood but a lower level of histamine. The role of the lungs in homeostasis of blood biogenic amines in the postresuscitation period is discussed.

[Evaluation of the efficacy of extracorporeal membrane oxygenation of animals with acute respiratory insufficiency]. / Otsenka éffektivnosti ékstrakorporal'noi membrannoi oksigenatsii uzhivotnykh s ostroi dykhatel'noi nedostatochnost'iu.

The efficiency of extracorporeal membrane oxygenation was studied for 2-3 hours in experiments on dogs with severe ventilatory respiratory failure. Extracorporeal oxygenation led to the decrease in arterial hypoxaemia and hypercapnia in animals. However, the variables did not reach the initial levels and were closer to normal values during veno-venous and not veno-arterial perfusion. During extracorporeal membrane oxygenation total systemic blood flow exceeded the initial level irrespective of the means of perfusion and total oxygen transport did not decline lower than the initial level. At the same time during veno-arterial perfusion oxygen delivery provided by the cardiac output decreased almost two-fold by the second hour of perfusion. This might be the reason for inadequate oxygen delivery to the brain and heart. 67% and 71% of animals survived after veno-arterial and veno-venous perfusion, respectively.