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Authors presented the results of experimental and clinical studies of effects of recombinant prourokinase on brain tissue, its toxicity and safety in intracerebral administration for lysis of hypertensive intracerebral hematomas. Experiments were performed in 64 rabbits. Histological specimens were examined in different periods after injection of prourokinase into white matter and into experimental hematoma. It is revealed that dose of 615 mg/kg causes minimal changes in cerebral tissue. Clinical study was based on analysis of puncture aspiration of intracerebral hematomas with local fibrinolysis performed in 275 patients with hemorrhagic stroke. Dynamics of MRI, clinical and laboratory parameters, coagulation, analysis of aspirated products of lysis were assessed. Authors showed that recombinant prourokinase and the drug "Puroplazan" are effective for local fibrinolysis. The drugs are non-toxic and non-allergenic and do not cause cerebral edema.

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Individual antithrombotic activities of superoxide dismutase (SOD) and sodium chondroitin sulfate (CHS) as well as the activities of covalent and noncovalent complexes of SOD with CHS were compared in a rat model of arterial thrombosis induced by ferrous chloride. Covalent conjugate of SOD with CHS exerted the most potent antithrombotic effect, which was associated with adsorption of the conjugate on the glycocalyx of the vascular wall cells and stability of the covalent bond between CHS and SOD subunits. Theoretical and practical directions in the investigation of SOD and CHS preparations are outlined.

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Distribution of recombinant pro-urokinase (PRU) in segments of blocked carotid arteries of rabbits was measured in 10, 20 and 30 minutes after i.v. administration of the RPU. Concentration of the latter in the bloodstream taken as 100% on the 3rd minute, after the infusion decreased to 42% in 10 min., 24% in 20 min., and 13% in 30 min. The RPU concentration decreased to 2% at the artery clamp point, to 20% at 10-15 cm from the clamp point, and remained constant for 10-30 min. A thrombolytic agent accumulated at the dead-end of the blocked artery, was not subject to rapid clearance in contrast to circulating pro-urokinase.

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The comparative antithrombotic activity of superoxide dismutase and chondroitin sulfate in the form of covalent or noncovalent complexes was studied on the rat arterial thrombosis induced by treatment of vessel with ferrous chloride solution. The covalent conjugate between superoxide dismutase and chondroitin sulfate has been shown to exert the highest antithrombotic effect. The higher antithrombotic activity of covalent conjugate is stipulated by its coupling on the glycocalyx of vascular wall and by the stability of the covalent bond between superoxide dismutase subunits and chondroitin sulfate.

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Conjunctive administration of the tissue-type plasminogen activator (t-PA) and the urokinase-fibrinogen covalent conjugate (UK-Fbg) was studied by the example of venous thrombosis in dogs. Comparing the effect of separate use of the two components, we observed the potentiation of thrombolytic effect induced by an i.v. bolus infusion administration of the tissue-type plasminogen activator (1 and 4 mg, respectively) combined with a bolus administration 15 min after the first injection of the 25,000 IU UK-Fbg. Faster-action and potentiation effects of thrombolysis were observed with the same administration scheme when the t-PA was used as bolus infusion (1 and 1 mg, respectively) combined with a bolus of the 250,000 IU fibrinogen-modified urokinase. The findings indicate an approach to the development of efficient thrombolytic compositions.

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Endotoxemia induced by gram-negative bacteria leads to endotoxic shock pathogenetically stemming from the integral component of the bacterial wall--lipid A. The study made to define the ability of lipid A monoclonal antibodies to correct hemodynamic disturbances due to endotoxemia in dog experiments showed the efficacy of the antibodies administration. ReLPS isolated from Salmonella Minnesota was used as an antigen. Administration of the complex monoclonal antibodies-endotoxin caused no hemodynamic impairment.

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The antithrombotic effect of fish oil (FO) cannot be explained by its action on platelets. FO may act on the activity of the fibrinolytic system. A food additive of the oil was studied for its effects on thrombosis and fibrinolysis in a canine model of experimental coronary thrombosis. During 4 weeks, 6 animals were fed a diet containing Sardinops sagax melanosticta oil (400 mg/kg/day) (omega 3-polyunsaturated fatty acids (omega 3-PUFA), 5 dogs had isocaloric amounts of olive oil (00), 5 animals were controls on a routine diet. Thrombosis was induced by anodal current, 170 mcA, through the silver electrode inserted into the coronary artery across its wall, thus contacting with the intima of the preconstricted left circumflex artery. Plasma levels of eicosapentaenoic (EPA) and docosahexaenoic acid (DHA) and euglobulin clot lysis time were determined before and after diet. The frequency of occlusion for 180 min after power turning-on was 5/5 in the 00 and control groups, but 1/5 in the FO group. Thus, dietary supplementation with FO which caused a substantial increase in plasma omega 3-PUFA prevented coronary artery occlusions without decreasing euglobulin clot lysis time. So, while producing antithrombotic effects, the oil failed to affect fibrinolysis in this model of thrombosis.

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The ultrasound contrast medium obtained by the original methods was administered into the left ventricular cavity and myocardium of 12 open-chest dogs by using a catheter. After its administration into the cavity there was its intensive contrast. When the ultrasound contrast was administered into the aortic root, the entire myocardium contrasted, on selective administrations of the contrast into the coronary arteries, the beds supplied by appropriate arteries contrasted. The ultrasound contrast study enabled the areas with impaired perfusion as echo-negative "filling defects" to be detected and mapped. The imaging of myocardial blood flow in tomographic sections and real time allows one to regard it promising for clinical use.

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Operation for mammary-coronary shunting was reproduced on experimental dogs. Myocardial perfusion during shunting was accomplished through a shunt, passing in the mammary artery and introduced into the distal part of the coronary artery through an incision. This allowed the use of extracorporeal circulation and the development of myocardial ischemia to be avoided. The method makes it possible to create stenoses in any part of the vascular block. The authors analysed the dependence between the coronary blood flow and the pressure in the left ventricle and aorta by means of a mathematical model, which made it possible to separate the effect produced on the coronary blood flow by such parameters as the resistance and capacity of the large vessels, resistance of small vessels, pressure of arrest of the blood flow, and extravascular compression.

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Mammary coronary bypass surgeries were performed in canine experiments. Myocardial perfusion was done via a shunt passing within the mammary artery and inserted into the distal portion of a coronary artery through a section, avoiding the application of extracorporeal circulation and myocardial ischemia. The method creates stenoses in any area of a vessel unit. A relationship was examined between coronary blood flow, left ventricular and aortic pressures by using a mathematical model that covers the effects of such parameters as resistance of great vessels, their capacity, minor vascular resistance, blood flow arrest and extravascular compression pressures on coronary blood flow.

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Activated C protein (ACP) is a physiological anticoagulant enzyme that is capable to inactivate factors Va and VIIIa, thereby having a wide spectrum of antithrombotic effects. Low-dose ACP was tested for its ability to affect anodic current-induced arterial thrombosis in the rat. ACP given in low doses (15 micrograms/kg, 7% of total C protein in the rat) was found to produce a marked antithrombotic effect. With this, the activated partial thromboplastin time remained virtually unchanged, and its antithrombotic action was equal to that of heparin administered in a dose of 125 U/kg. In the authors' opinion, ACP may form the basis for designing a highly effective antithrombotic agent.

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We analysed the relationship between artery pressure (AP) and coronary flow (F) in the canine coronary bed, using an electrical analog model of the coronary circulation. The model contained a capacitance of epicardial vessels, input and terminal resistances, diode, and the number of e.m.f., simulated the intramyocardial pressure and zero-flow pressure. These e.m.f. are assumed to be a linear functions of left ventricular and aortic pressure. The value of coronary blood flow was calculated from experimental curves of AP and LVP and setting parameters. Good agreement was obtained between theoretical and experimental curves of coronary blood flow.

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The effect of norepinephrine (NE) on reactive myocardial hyperemia (RH) after a brief (20 sec) flow arrest was studied in 9 closed-chest anesthetized dogs. NE infusion into the left ventricle resulted in the increase of RH peak during coronary flow and the elevation of the left ventricular pressure and its first derivative. The increased coronary dilatation may be explained by the activation of beta 1-adrenergic myocardial receptors. RH peak decreased later, with the coronary flow, left ventricular pressure and its first derivative returning to the control level. This RH decrease can be explained by the activation of alpha-adrenergic receptors of the coronary vessels and the competition between alpha-receptors for vasoconstriction and metabolic vasodilatation.

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