The inception of the North American Society of Biorheology and the growth of biorheology as an organized science.
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Biomedical subjects
Publications and source records attributed to A L Copley.
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An attempt is made by the author to show that biorheology and certain of its branches are expected to contribute towards a better understanding of mechanisms concerning beneficial effects known in the practice of acupuncture. Rheology, a branch of physics, founded as an organized science in 1929, is defined as the science of deformation and flow of matter. Biorheology comprises the science of deformation and flow of biological systems or of materials of biological significance. Recently, the author considered biorheology to be the missing link between the life sciences. Hemorheology, at present its most active branch, is concerned with the rheological (deformation and flow) properties of blood, including its cellular and plasmatic components, and of the structures of the vessel wall with which blood and its components come into direct contact. Hemorheology is the study of how the components of blood and of the vessel wall can function and interact rheologically. In 1981, the author defined the entity of the blood and its more or less leaky envelopes, the variety of blood vessels in a variety of tissues and organs, as an organ, named the 'vessel-blood organ'. It is a special organ penetrating all other organs and can be likened to some extent to the nervous system. Hemorheology is thus the rheology of the vessel-blood organ, its constituents and of the processes involved in both its two portions as well as in their interactions. There is an extension of hemorheology, termed recently by the author 'parahemorheology', which deals with processes and flow occurring within the interstitial spaces, across the parenchymal cell membranes, the lymph and the channels or lymphatics, in which it is contained, and its walls. Thus parahemorheology is intertwined with hemorheology. Applications of biorheology to the theory and practice of different fields in medicine is called medical or clinical biorheology. It is expected that clinical hemorheology and clinical parahemorheology are of particular significance in research on acupuncture. Such considerations have thus far not been taken into account in studies of mechanisms pertaining to acupuncture. It is obvious that biorheological processes occur in patients as a result of acupuncture, for example the release of muscular spasm. The crucial barrier in transcapillary transport is considered by the author to be the endoendothelial fibrin(ogenin) lining. Fibrinogenin is the term for the aggregation and gelation of fibrinogen without thrombin participation. The field of electro-biorheology is closely associated with parahemorheology.(ABSTRACT TRUNCATED AT 400 WORDS)
In earlier studies using a modified Weissenberg Rheogoniometer, we found decreased rigidity or torque values (tau) in surface layers of heparin plasma, when compared to tau of oxalate plasma from the same blood withdrawal (Thrombosis Res. 1, 1-17, 1972). In subsequent studies of the viscoelasticity of surface layers of highly purified fibrinogen (97-100% clottability) of human and bovine origin, we found, with some heparins, marked lowering of surface viscous moduli (eta's) and of surface elastic moduli (Gs). With some heparins no changes in tau, eta's and Gs occurred. Certain low molecular weight (LMW) preparations of heparins showed decreases, but some did not. This is also the case with heparins of low and high affinity for antithrombin. Calcium heparin and Ca2+ alone always increased eta's and Gs, when added to the fibrinogen system. N-desulfated heparin both decreased or did not change eta's and Gs. Preparations of fibrinogen in dog plasma, to which sodium heparin was added, resulted in a decrease of tau values. These results appear to emphasize that plasma proteins other than fibrinogen, and other plasma constituents, may affect surface hemorheological values. These findings suggest needed interface studies of fibrinogen systems to which plasma or plasma constituents are added. We found also that other substances, i.e., dextran MW 20,000; dextran sulfate MW 17,000; sodium hyaluronate and depolymerized hyaluronate decreased tau, eta's and Gs markedly. Recent findings in the literature are discussed in relation to thrombogenesis in which fibrinogenin gelation is considered as the initial phase of blood clotting. Fibrinogenin is the new term for initial fibrinogen aggregation and subsequent fibrinogen gelation without thrombin participation. The inhibition of fibrinogenin formation extra vivum is considered to be a valid indicator of antithrombogenic activity of substances which play a significant role in investigations on the therapy and prevention of thrombotic conditions.
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The interface between the two portions of the 'vessel-blood organ', viz., the vessel wall and the circulating blood, is considered by the author to be the endoendothelial fibrin lining (EEFL). The view that the endothelium, consisting of the endothelial cells and the interendothelial cement substance, is the primary filtration barrier in capillary permeability (CP) is no longer tenable. There is considerable evidence that the primary barrier is an endocapillary protein layer, originally postulated by Danielli in 1940. Copley considered this layer to be identical with the EEFL formed in the more or less immobile portion of the plasmatic zone in close proximity to the vessel wall. Processes of fibrin formation and fibrinolysis can occur there homeostatically, undisturbed by the flow of blood. The fibrinopeptides and plasminopeptides, freed at this site by the conversion of fibrinogen to fibrin and of plasminogen to plasmin, respectively, were reported by Copley et al in 1966 to augment CP. These peptides thus take part in the steadily occurring normal physiological CP. This is facilitated by the porosity of the EEFL due to the network or gel structure of fibrin strands. The author's concept that the EEFL acts as the primary barrier, controlling transendothelial transport and transport across the basement membrane (BM), is discussed on the basis of older and recent findings by several investigators. In particular, the BM is dealt with in some detail as a barrier. Emphasis is placed on the existence of fibrin as a main constituent of the BM, hitherto not generally known. This was demonstrated by direct evidence in the production of (non-thrombocytopenic) vascular purpura with fibrin antiserum. Numerous tiny foci of fibrin(ogenin) gels are expected to stud the BM. Augmented capillary fragility (CF) due to increased fibrinolysis of many of these focal fibrin gels result in petechial hemorrhages. CF and CP are physical properties of the blood capillary wall which behave antagonistically and are controlled by fibrin formation and fibrinolysis, steadily occurring in the vascular layers including the BM. This barrier secures the integrity of the capillary wall by preventing extravasation of blood or hemorrhages. New experimental approaches to verify the detection of fibrin in the microstructure of the capillary wall are proposed. Moreover, hemorheological experimentation, models and treatments are needed to establish whether or not the EEFL is the crucial, critical barrier in CP, as proposed.
The theories and spatial concepts of Karl Weissenberg have been applied to the science of biorheology by employing the Weissenberg Rheogoniometer. Two main types of experimental methods have been used for the characterization of the bulk shear properties of biorheological fluids: (A) In continuous laminar shearing motion, the tangential and normal components of stress are measured at a series of rates of shear. From these parameters, the apparent viscosity, an elastic modulus and a recoverable strain, are calculated as functions of the rate of shear. In this continuous shear experiment, the physical structure present in the material at any given rate of shear may be quite different from the material in its rest state or at other rates of shear. (B) In harmonic oscillatory motion, the material is subjected to a harmonic laminar shear about its rest state at a number of frequencies and small strain amplitudes. From these experiments the dynamic moduli of viscosity and elasticity are calculated. Preparations of biological materials, such as whole blood and systems of blood components, both in health and disease states, have been investigated using methods A and B, together with studies of surface layers of plasma proteins at interfaces.
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Hemorheological studies were made on surface layers of solutions of highly purified human fibrinogen, to which low molecular weight (LMW) heparins, as well as chondroitins A, B and C were added. The surface viscous (eta's) and elastic (Gs) moduli of these fibrinogen systems were measured with a modified Weissenberg Rheogoniometer. Our findings show that n's and Gs of these heparin-fibrinogen and chondroitin-fibrinogen surface systems were markedly decreased as compared to the fibrinogen control. Heparin of MW 4400 exhibited about 30 per cent decrease, while heparins of MW 5300 and 5900 had decreases of approximately 75 per cent in n's and Gs. The three chondroitins A, B and C were found to reduce the n's and Gs by about 40 per cent. The surface layers of fibrinogen, which are surface gels, constitute the clotting of fibrinogen without thrombin participation. Such so-called 'fibrinogenin' formation is considered by Copley to initiate thrombosis. The LMW heparins and the chondroitins tested, which we found to inhibit fibrinogen formation, may therefore be expected to act as antithrombotic agents. Thus, LMW heparins and chondroitins A, B and C may play important roles in the prevention of thrombosis.
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The author's theory of the endoendothelial fibrin lining (EEFL), first advanced in 1953 and developed by him ever since, localizes the homeostasis between steady fibrin formation and deposition, or 'fibrination', and continuous fibrinolysis in the more or less immobile portion of the plasmatic zone next to the vessel wall. In 1971, the author advanced, in relation to the EEFL, the theory of fibrinogen gel clotting without thrombin action or 'fibrinogenin' formation in vivo. Considerable direct and indirect experimental evidence, secured by the author and by several other investigators, advanced markedly the knowledge of the normal physiology and the pathophysiology of various disease processes involving the vessel wall and blood circulation. The information presented is an extension to that given in the author's recent overview (Clin. Hemorheology 1, 9-72, 1981). It deals both with new data by several investigators including those by the author, as well as with older data from the literature. The author maintained already in 1960 that the blood together with the blood vessels, in which it circulates, constitute 'an entity'. In 1981 he postulated this entity to be a very special organ, named conveniently 'vessel-blood organ', which is ubiquitous and penetrates all other organs and adjacent tissues. The EEFL of the vessel-blood organ is considered by the author as the crucial critical interface between the blood and the vessel wall. It is the primary barrier, followed by the endothelium (comprising the endothelial cells and the interendothelial cement substance which contains or is identical with 'cement fibrin') and the basement membrane for the exchanges between the blood, the vessel wall and its surrounding tissues and spaces. The EEFL acts as anticoagulant, is antithrombogenic, maintains vascular patency and aids cardiac action by decreasing significantly the apparent viscosity of blood, referred to in the literature as the 'Copley-Scott Blair phenomenon'. A new concept of leukocyte emigration traversing the capillary wall is presented, affecting focal fibrinolysis of the EEFL and of fibrin contained in the interendothelial cement substance and in the basement membrane. The physical property of capillary (or vascular) permeability is related to the existence of the EEFL, since, as found by Copley et al, both fibrinopeptides, liberated in the transition of fibrinogen to fibrin, and plasminopeptides, freed in the conversion of plasminogen to plasmin, enhance capillary permeability. Capillary fragility, which is antagonistic to capillary permeability, is in great part due to fibrinolytic action on fibrin as a constituent of the basement membrane.(ABSTRACT TRUNCATED AT 400 WORDS)
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