[Patterns of preventive activities in medical institutions].

Results of developing and implementing, in experiment conditions, of primary medical sanitary care program targeted to cardiovascular patients is presented. Organizational functional model of schools for patients with arterial hypertension and ischemic heart disease is approved. Medical social and economic efficiency of these schools activities is proved.

Changes in the constant potential in brain structures in rats during focal ischemia and systemic hypoxia.

The functional consequences of spreading depression (SD) during the evolution of ischemic damage was studied in two models: focal cortical ischemia induced by photothrombosis of the middle cerebral artery (MCA) and systemic hypoxia induced by 0.8% carbon monoxide (CO). These studies showed that cortical waves of SD, arising spontaneously during MCA thrombosis and after arterial occlusion delayed thrombus formation and promoted the establishment of a collateral blood supply in the perifocal zone of ischemic lesions. The underlying mechanism consisted of episodes of intense vasodilation at the decay phase of every wave of SD. Respiration of 0.8% CO increased the blood carboxyhemoglobin level to 50-60%. In lightly anesthetized rats (pentobarbital 20 mg/kg), cortical and subcortical spontaneous waves of SD were transformed into stable hypoxic depolarization, leading to death of 60% of the animals or severe lesions of the central nervous system, in 20% of animals. Increases in the level of anesthesia (50 mg/kg anesthetic) prevented the spontaneous appearance of SD during long-lasting exposure to CO. In these conditions, experimentally induced waves of SD demonstrated that the hippocampus has a high sensitivity to moderate levels of hypoxia. The duration of hypoxic depolarization of the hippocampus, provoking a single SD wave, reached 30-60 min. Selective neuron damage in field CA1 was seen 30 days after hypoxia. Additionally, the left hippocampus of rats frequently showed profound morphological lesions in the form of "granules." Cerebrolysine (2.5 ml/kg daily for 10 days) completely prevented the formation of these lesions.

Hippocampal damage induced by carbon monoxide poisoning and spreading depression is alleviated by chronic treatment with brain derived polypeptides.

A model of acute carbon monoxide poisoning combined with spreading depression (SD) induced metabolic stress was used to examine the protective effects of cerebrolysin (CL) on the development of electrophysiological, behavioral and morphological signs of hypoxic damage. Capillary electrodes were implanted into the neocortex and hippocampus of anesthetized rats which were then exposed for 90 min to breathing of 0.8% to 0.5% CO, while 3 to 4 waves of cortical and hippocampal SD were elicited by microinjections of 5% KCl. Duration of SD-provoked depolarization of cerebral cortex and hippocampus was noted. Nine and 18 to 19 days later propagation of SD waves was recorded with the same electrodes and decrease of their amplitude was used as an index of brain damage which was significant in the hippocampus but not in the cortex. CL-treatment (2.5 ml/kg per day) started after CO administration and continued for 14 days significantly improved hippocampal recovery manifested by increased amplitude of SD waves. Behavioral tests performed 10 and 20 days after CO poisoning in the Morris water maze revealed better performance (escape latency 7 s) in the CL-treated than in untreated animals (14 s). Morphological analysis showed marked damage in the hippocampus consonant with electrophysiological and behavioral findings in the same animals. No apparent histological damage was found in rats exposed to CO inhalation alone without the additional SD-provoked depolarization. It is concluded that chronic CL-treatment enhances recovery of hippocampal tissue after hypoxic damage of intermediate severity.

[Shifts in the constant potential in the structures of the rat brain in focal ischemia and systemic hypoxia]. / Sdvigi postoiannogo potentsiala v strukturakh golovnogo mozga krys pri fokal'noi ishemii i sistemnoi gipoksii.

The role of spreading depression (SD) in the development of ischemic brain damage in rats was studied in two models: focal cortical ischemia provoked by a photothrombotic occlusion of the middle cerebral artery (MCA) and systemic hypoxia induced by breathing with 0.8% carbon monoxide (CO). Spontaneous cortical SD waves occurring during illumination were found to delay the irreversible MCA occlusion. Thrombosis was probably prevented by episodes of striking vasodilation and hyperemia lasting for 1-2 min and accompanying every SD wave. The SD-induced hyperemia after permanent MCA occlusion seems to improve the oxygen supply of the penumbra zone. During hypoxia induced by one-hour respiration with 0.8% CO, COHb saturation of the blood reached 50-60%. SD waves occurred in different brain regions of lightly anesthetized rats (pentobarbital, 20 mg/kg) changed under the above conditions into prolonged depolarizations (HDs) which led to a substantial increase in animals' mortality (60%). The SDs evoked in the cortex and hippocampus of deeply anesthetized rats (pentobarbital, 50 mg/kg) showed that hippocampus became highly vulnerable by CO hypoxia. Duration of the SD-provoked HDs often reached 30-60 min after a single SD wave. Decreased cell density was found in CA1 area of the hippocampus 20-30 days after the CD-enhanced CO hypoxia. Cerebrolysin (2.5 ml/kg daily, during 10 days) prevented from severe hippocampal injury (formation of granulomas) usually seen in the left hemisphere of rats not treated with cerebrolysin.

[The persistent negative potential provoked in different structures of the rat brain by a single wave of spreading cortical depression]. / Ustoichivyi negativnyi potentsial, provotsiruemyi v razlichnykh strukturakh golovnogo mozga krysy odinochnoi korkovoi volnoi rasprostraniaiushcheisia depressii.

The persistent negative potential (PNP) developed after a single wave of cortical spreading depression (SD) in the cortex, hippocampus, thalamus, and caudate nucleus. The PNP lasted for about 3-4 hours, its amplitude was 6-7 mV in the ipsilateral and 3-4 mV in the contralateral structures. After development of bilateral primary cortical SD waves the amplitudes of the respective PNP were summed up and reached 9-11 mV. However, after the repeated waves of cortical SD produced with 15-30-min intervals, the PNP level remained unchanged. We think that the PNP is an electrographic manifestation of the well known persistent vasoconstriction after a single wave of cortical SD. It seems to be related with reticular activation due to functional decortication.

The effect of MK-801 and of brain-derived polypeptides on the development of ischemic lesion induced by photothrombotic occlusion of the distal middle cerebral artery in rats.

The effect of neuroprotective drugs on the early and late electrophysiological manifestations of photothrombotic occlusion of distal branches of middle cerebral artery was studied in rats treated with MK-801 and Cerebrolysin (CL). DC potentials were recorded from the irradiated cortex (ischemic core), from the adjacent penumbra zone and from remote intact cortex. Irradiation elicited after a few minutes of spontaneous spreading depression (SD) waves followed during 10-15 min by focal ischemic depolarization (FID) developing in the irradiated cortex and spreading into the perifocal areas. While the core FID amplitude reached about 30 mV and decayed during subsequent 2 h to 10-13 mV, FID in the penumbra zone was broken by periods of partial repolarization and returned during 30-90 min almost to baseline. At the same time, generation of spontaneous SD waves almost stopped. MK-801 (0.5 mg/kg, i.p., 45 min after ischemia) blocked SD waves, but did not shorten penumbra FID, the decay of which was slowed down to the rate found in the ischemic core. CL treatment (2.5 ml/kg, i.p. , 1 h after ischemia) did not influence FID in the acute phase of the experiment, but its 10-day administration facilitated post-ischemic recovery indicated by higher amplitude of evoked SD waves penetrating into the former penumbra zone. Morphological examination showed that the volume of total and partial necrosis was increased in the MK-801 group and marginally reduced in the CL group. It is suggested that the absence of the SD-induced hyperperfusion episodes in MK-801-treated rats may accelerate perifocal thrombotization in this model of focal ischemia.