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Correction of the Blood Properties

#G-753


Investigation of Possible Qualitative Improvement of the Blood Supply of the Tissues via Direct Correction of the Blood’s Rheological Properties

Tech Area / Field

  • PHY-NGD/Fluid Mechanics and Gas Dynamics/Physics
  • MED-DRG/Drug Discovery/Medicine
  • BIO-CHM/Biochemistry/Biotechnology

Status
3 Approved without Funding

Registration date
25.06.2001

Leading Institute
Ministry of Education and Science of Georgia / Beritashvili Institute of Physiology, Georgia, Tbilisi

Supporting institutes

  • ReocoR Laboratories Ltd., Georgia, Tbilisi

Collaborators

  • Tokyo Medical University/ Hachiohji Medical Center /Ncuroscience Laboratory, Japan, Tokyo\nUniversity College London/Royal Free and University College Medical School, UK, London\nThe Johns Hopkins Medical Institutions, USA, MD, Baltimore\nJOHNS HOPKINS Medicine/Neurology/Division of Brain Injury Outcomes, USA, MD, Baltimore\nWallenberg Neuroscience Centre, Sweden, Lund

Project summary

The goal of the Project is development of new technology (means and methodology) for protection of tissues and organs (primarily the brain) from a deficiency of blood supply of varying degrees, including massive bloodletting. The Project is based on an original method of determination of the blood’s rheological properties in vivo and new methodology of direct correction of hemorheological properties using the original composition.

The important role of the blood’s rheological properties for provision of the normal functional state of the organism, and mostly for the cardiovascular system, is now generally accepted. Usually, the investigation of the blood’s rheological properties has been carried out so far using traditional methods of viscosimetry. However, the "conventionality" of the extrapolation of model experiment results, performed on viscometers, agregometers etc., should be taken into account, as the blood fluidity in these devices essentially differs from the blood’s fluidity in living microvessels.

The application of substances, which effect the blood’s fluidity (rheology), has been intensively studied since the 1970s, when a number of works appeared, dedicated to the study of the effect of various polymers, particularly Pluronich F-68 or its analogs. Special attention was paid to mechanical or chemical injury to the components of the blood. The basic results of these studies, in the opinion of the authors, testified the effectiveness of the application of copolymers only in the cases of abnormally high viscosity in patients with specific pathologic states. Additionally, the insignificant effect of polymers on the viscosity of the blood of healthy people was emphasized. Moreover, in experiments on rabbits a double increase in the blood supply to ischematized brain tissue was demonstrated, in the absence of a noticeable (measured) effect of the decrease of viscosity after application of these polymers.

Obviously, the effectiveness of the application of these preparations was in fact limited by the absence of direct quantitative estimations of the parameters, which in totality determine the mechanism of the formation of the blood’s fluidity in vivo. The paradox in the above experimental data confirms the inevitability of our approaches, which are based on the specific properties, which actually exist in living microvessels - constantly changing characteristics of the rheological behavior of the blood in the microvessels.

The basis of the proposed project involves the following original methods and approaches, elaborated by V.Mamisashvili and his colleagues:

— in vivo cinemicrography and subsequent analysis of inpidual frames for quantitative estimation of parameters, which form and characterize the «rheological situation»: e.g. velocity profile, trajectory, orientation of inpidual erythrocytes, creation of erythrocyte agglomerates, pulsation of blood flow velocities and concentration of erythrocytes in microvessels with diameters 20-120mkm in vivo (Mamisashvili et al., 1980, 1982, 1984, 1987, 1992), using an original “biological model” (Author's certificate USSR state committee on deals of inventions and discoveries № 1118368, 15.06.1984 );

— determination of blood flow velocity profiles in microvessels in vivo using MPV-Compact-Vel, [“Leitz”, Germany], (Mamisashvili, 1987; V.Mamisashvili, N.Mchedlishvili, 1992, 1999);

— monitoring of the blood's viscosity properties in microvessels in vivo, determining the “index of the blood’s rheological behavior” (Georgian Patent No 1577, 29.04.99);

— quantitative estimation of the “effective viscosity” in vivo;

— evaluation of laws of blood flow in inpidual vessels of microcirculatory system in vivo;

— possible direct correction of essentially rheological properties in practice (i.e. “effective viscosity”) and, as a result – a change in the law of blood flow by original composition (now at a stage of patent evaluation).

These investigations gave a direct, quantitative estimation of the parameters determining, in totality, the mechanism of the formation of the blood’s rheological properties in vivo. It concerns, first of all, the microcirculation system, since the most important non-Newtonian properties of the blood are manifested in the vessels of the microvasculature, which constantly change the law of blood flow in the absence of any exo- or endogenous pathogenic factors. These changes are caused by the actually existing specific properties of blood flow in living microvessels. Obtained results confirmed the possibility to directly change the blood’s rheological behavior and, as a result, toqualitatively improve the blood supply to tissues.

These studies are multidisciplinary, involving the following scientific fields: a) Biophysics of Circulation (haemodynamics and rheology); physiology and pathology of circulation; b) organic chemistry, chemistry of high-molecular combinations; c) biochemistry and neurochemistry; d) neurophysiology. The experiments will be carried out on the basis of “The Biophysics of the Circulation” group, Laboratories of Neurochemistry and Human Psychophysiology of the I.Beritashvili Institute of Physiology. 13 scientific employees will take part in this work. 12 participants of the project were earlier engaged in strategic defense issues.

The Project Manager, Valeri A. Mamisashvili, is the head of the “The Biophysics of Circulation” group, candidate of Biological Sci., the author of about 60 articles on the physiology of brain circulation and the mechanisms of its regulation, circulation haemodinamics and hemorheology. During the last 20 years he has been working on the mechanisms forming the blood’s rheological properties, using original approaches and methods, which he has developed himself. Mamisashvili is the author of the new acknowledged concept of the action on the organism’s functional state by direct correction of the blood’s rheological properties (Resume of Commission of Experts of Georgian Ministry of Healthcare and Social Security, 07.28.2000). Prof. David G.Mikeladze, the head of the Neurochemistry Laboratory, is the leading expert in Biochemistry and Neurochemistry. Prof. Victor I.Maloletnev, the head of the Laboratory of Human Psychophysiology, is a specialist in the investigation of the changes of functional state of the Central Nervous System, especially in different stressogenic conditions. Candidate of Chemical Sci., Zurab T.Japaridze is the leading expert in Georgia in organic chemistry and chemistry of high-molecular combination.

The proposed project is based on the results of studies, which are the object of the author’s (i.e. Project Manager V.A.Mamasashvili) intellectual property. The legal support of the project, at all stages of realization, will be performed by the experts of Reocor Laboratories Ltd. David Bibiluri and Teimuraz Kvernadze are the leading experts in Georgia for Intellectual Property Rights Protection and Management.

Conventional methods will be used to solve the following project tasks:

— evaluation of the possibility to change the rheological characteristics of the blood flow;

— development of a working model of original composition and creation of a new effective model of the composition with essentially hemorheological effects;

— biochemical analysis of elaborated compositions;

— polyphysiographic monitoring of the main physiological functions: electroencephalography, electrocardiography, control of respiration, haemodynamical parameters of the circulatory system (system arterial pressure, system venous pressure, intensity of the brain blood supply etc.);

— investigation of the consequences of the hemorheological effect of elaborated composition on the basic parameters of circulation;

— definition of the criteria for evaluation of the functional state of the organism on the critical stage of hemorrhagic shock (differentiation of the states of “clinical death” and “brain death”);

— study of the dynamics of the parameters of vital physiological function restoration during reanimation by means of the proposed chemical composition;

Rats and dogs will be used in the experiments. Experimental models: the original composition allows for the creation of a unique «reversible» model of varying degree of “ischemia” (e.g. hypoxia, coma, hemorrhagic and hypovolemic shocks, clinical and cerebral death etc.) caused by massive bloodletting.


All experiments on animals will be carried out in conformance with corresponding international conventions and agreements related to the protection of animals.

The minimal dosage of chemical combinations, developed in this project, will be employed in the experiments.

Expected Results and their Application The new chemical composition and the mode of its application, which will be worked out during realization of the project, enables the following results:

— The new technology of preservation of the organism from the consequences of massive bloodletting, facilitating a reduciton in mortality among civilian trauma victims and achieving survival without multiple organ failure and brain damage;

— New approach to the therapy of strokes (ischemic or hemorrhagic) at the earliest stages of disturbance of the brain circulation;

— Increase in the time of evacuation after accident by at least 6 hours without any current blood substitutes or special devices (artificial circulation and respiration);

— Unique experimental model of “reversible ischemia” to study the consequences of massive bloodletting, modeling disaster situations and for risk management studies;

— Psychophysiologic and psychometric tests for evaluation of brain function restoration during and after hemorrhagic and hypovolemic shocks;

— An original composition, the PRODRAG – the basis for developing a principally new class of pharmacy with an essentially hemorheological effect.


Application of this approach creates premises to challenge the adopted strategies of critical medical care (especially in disaster situations).
The Project will help solve national and international problems, adequate to civil needs.


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The International Science and Technology Center (ISTC) is an intergovernmental organization connecting scientists from Kazakhstan, Armenia, Tajikistan, Kyrgyzstan, and Georgia with their peers and research organizations in the EU, Japan, Republic of Korea, Norway and the United States.

 

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