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Biomedical subjects

L Dintenfass

Publications and source records attributed to L Dintenfass.

At least 19 recordsLinked to original sources

Blood as a near-"ideal" emulsion: a retrospective on the concept of the red cell as a fluid drop, its implications for the structure of the red cell membrane.

Although the question whether the red cell is fluid or solid has been discussed since 17th century, it was the author's measurement of the relative viscosity of blood in 1960's that supplied the first direct evidence that the red cell interior is fluid. Furthermore, through his application of the equations of Taylor and, later, Oldroyd, to this problem, it became evident that, for the red cell to exhibit fluid-drop-like behavior, the membrane must also be fluid. This led to his concept of the red cell membrane as a complex two-phase structure (lipoprotein micelles and two-dimensional protein networks) which was similar to the one accepted nearly a decade later. The requirements of the theory of ideal emulsions that the shear stress be transmitted into the cell interior via low viscosity membrane, are met in the later work of other investigators using the concept of a tank-treading membrane having viscoelastic properties. This paper reviews the original work of the author which led to the development of an equation for the relative viscosity of blood as a function of volume concentration, C: nr = (1 - TkC)-2.5, valid at shear rates above 180 sec-1, in which T is the Taylor factor which gives a measure of fluidity of the red cell, and k is a plasma trapping factor. Both T and k increase with increasing rigidity of the red cell. Finally, the effect of the membrane viewed as a complex two-phase fluid, on the rheology of the red cell is discussed.

Blood Viscosity

A new outlook on body fluid viscosity and cell function: concluding remarks and discussion.

The area neglected so far in the fields of clinical and theoretical haemorheology is that of interaction between viscosity and chemical reactions in the cells. The reintroduction of teinochemical principle opens entirely new doors for investigation both in vitro and in vivo. Effect of extracellular fluid viscosity on synthesis (i.e. lipids) and on possible enzymatic and catalytic functions influences our opinion that haemorheology has to go back to fundamentals.

Animals

Modifications of blood rheology during aging and age-related pathological conditions.

In principle there should not be any increase of blood viscosity factors (plasma viscosity, blood viscosity, aggregation of red blood cells, rigidity of red blood cells, dynamic thrombus formation) with aging in a healthy population. Such an increase would be due to pathological caused and not to aging per se. The pathological causes of the increase in the blood viscosity factors often observed in the elderly could be ascribed to the following: use of drugs (e.g. cigarette smoking); lack of exercise; unbalanced diet; psychological states such as anxiety and depression; presence of diseases such as heart disease or cancer or diabetes (although these disorders have the same effect in a younger population). The principal viscosity factors are explained, and their role in tissue perfusion, occlusions, infarctions and other disorders is described. This review will hopefully serve as an introduction to the studies of the haemorheology of aging. A counteraction of the elevation of blood viscosity factors might be helpful in ameliorating many diseases typical of aging, and should allow elderly people to remain active much longer.

Aging

Aggregation of red cells in disease: some deductions and speculations based on results of "ARC" experiment on the space shuttle "Discovery" STS 51-C.

Experiment on STS 51-C in January 1985, carried out on blood samples obtained from patients with heart disease, diabetes, hyperlipidaemia and cancer showed that, under zero gravity, the morphology of red cell aggregates aggregates was normal, in contradistinction to the parallel and simultaneous observations under 1 g, which showed large and unorientated clumps of red cells. As such clumps could be considered of disadvantage in the microcirculation and tissue perfusion, the zero gravity observations were significant in a number of ways. In particular, a preliminary deduction (subject to further zero g experimentation) was that cell-cell interaction and adhesion are affected by zero gravity, and that most likely the microarchitecture of the cell membrane is modified; and that probably the receptors, their position and/or activity, are affected by zero gravity. Of particular interest could be a possible change in the properties of the discrete surface areas which respond preferentially to specific macromolecules (or ligands). There is a dissonance between these in vitro results and theoretical deductions on flow in the microcirculations by Oka, and as well of deductions on space sickness by Dintenfass, both assuming a disabling effect of zero g on the in vivo microcirculation. This dissonance should be explored, as effect of zero g might be different on blood flow in vivo and in vitro. However, the data available from the in vitro experiment suggest that studies in immunology and oncology might be enriched by zero gravity findings; and that studies under zero gravity might open a new avenue of research in these important fields.

Blood Viscosity

Execution of "ARC" experiment on space shuttle "Discovery" STS 51-C: some results on aggregation of red blood cells under zero gravity.

A project on "Aggregation of Red Cells" has been accepted by NASA in 1977. An automated slit-capillary photo-viscometer has been designed during 1979-1984, and its last version met NASA's space hazards requirements. The 'heart' of instrument is a set of two highly polished glass plates, spaced by a gap of 12.5 micrometers. An original drum-like infusion pump allows utilization of up to eight blood samples. During a sequential process, blood flows through the slit, and then stops to allow formation of aggregates. Micro- and macro-photography is carried out, and 500 photographs are obtained. Blood from normal donors and patients with history of ischaemic heart disease, colon cancer, juvenile-onset diabetes, hyperlipidaemia, etc., is anticoagulated and adjusted to haematocrit of 0.30 using native plasma. Samples are divided, and infused into the 'flight' and 'ground' instruments. Prior to experiment temp. is 5 degrees C; temp. during experiment is 25 degrees C. Experiments took place on 24-25 January 1985, on the middeck of space shuttle 'Discovery'. Subsequent results showed that red blood cells do not change shape under zero gravity; that aggregation of red cells does take place; that aggregates in pathologic blood show morphology of normal rouleaux under zero gravity, while identical blood shows clumps of red cells on the ground. The latter observation suggests that zero gravity might affect cell-to-cell interaction, and perhaps microstructure of the cell membrane. These aspects must remain however tentative till a confirmation by subsequent experiments can be obtained.

Adult

Red cell aggregation in cardiovascular diseases and crucial role of inversion phenomenon.

Perfusion of the heart muscle remains an important area of studies fraught with great difficulties. An analogue of capillary system has been organized by using in vitro flow of blood from the heart patients in a slit-capillary photo-viscometer. The rate of aggregation of red cells and the morphology of aggregates have been observed and quantitated in representative cases. A possible role of the sludge-like aggregates is discussed from the viewpoint of the "inversion phenomenon" which amplifies resistance to flow as a function of rheology (rigidity or deformability) of cell aggregates and single cells. This pattern might be alike that of arterial spasm or can serve as a model for capillary occlusions. A description is given of the new instrument, the slit-capillary photo-viscometer, and stereological parameters obtained in macro- and micro-photography are included. Linear regressions of such parameters against stasis time are highly significant, showing correlation coefficient up to 0.99. These regressions can be compared for slopes and elevations observed in different blood samples, with significance up to 0.001.

Blood Viscosity

Methods and instrumentation used in practice of clinical haemorheology.

The aim of practice of clinical haemorheology is to study patients who might present themselves with or without any clinical symptoms but who might suffer from silent or overt cardiovascular disorders, some forms of cancer, anxiety, etc. A presence and a prognosis of these disorders are linked to an increase and/or abnormality of one or more of the blood viscosity factors: blood viscosity, plasma viscosity, red cell aggregation and rigidity, platelet aggregation, ability for formation of thrombi, flow instability, etc. Hyperviscosaemia might be present in spite of normal or low viscosity of the whole blood. Different disorders can be described by 'profiles of viscosity factors' which form a rheological fingerprint specific to a particular disease or a group of disorders. Determination of viscosity factors is carried out utilizing a series of instruments: (a) rotational viscometers, (b) capillary viscometers, (c) erythrocyte sedimentation tubes in 20C and 37C water tanks, (d) variable frequency thrombo-viscometer, (e) slit-capillary photo-viscometer, etc. One known factor which is not measured routinely is 'inversion phenomenon', and this is due to complexity and expense of measurements. Biochemical studies, including fibrinogen assay and estimation of ABO blood groups, are carried out. Effect of drugs on blood viscosity factors can be studied in vitro or in vivo.

Aged

Effect of microrheology of blood on the apparent flow instability in a rotational viscometer.

Flow instability (formation of vortices and a concurrent increase in the apparent viscosity) was studied in the rotational rhombospheroid viscometer of 3 degrees, 5 degrees and 10 degrees gaps over a range of speeds from 10 to 300 r.p.m.. Comparisons between different blood systems were carried out mainly at 250 r.p.m. Experiments were carried out on blood samples obtained directly from human subjects, or from the Blood Bank, or from horses. Reconstituted suspensions of red cells in albumin or dextran were also used. Apparent flow instability was found to be not solely a function of blood viscosity, but a multiple function of many viscosity factors or blood subphases, including instability-decreasing factors such as haematocrit and aggregation of red cells; and instability-increasing factors such as rigidity of red cells; and thus specific to and characteristic of individual blood samples. Apparent instability can be described by multiple regressions as a function, Z, of red cell rigidity, Tk, blood viscosity, napp, and aggregation of red cells, AG; for example: Z = -28.29 + 26.24 Tk + 0.109 napp (r = 0.816; P less than 0.001), or Z = 5.90 - 0.0165 AG - 0.752 napp (r = 0.573; P less than 0.05). The apparent instability can be seen only in one-third of blood samples obtained from horses, and in more than half of blood samples obtained from human donors; majority of human donors shows apparent instability below 3 per cent.

Animals

Plasma and blood viscosities, and aggregation of red cells in racehorses.

Nineteen racehorses have been studied for haemorheologic factors as earlier studies showed a definite correlation between physical fitness and these factors in humans. Results included individual values for all viscosity factors, and the arithmetic means, the latter showing 4.70 +/- 0.49 cP for blood viscosity measured at a shear rate of 180 s-1; 1.100 +/- 0.048 cP for plasma viscosity; 1.045 +/- 0.063 for the rigidity of red cells defined by term 'Tk'; 42.2 +/- 4.1% haematocrit; 290 +/- 39 mg per 100 ml for fibrinogen level; and 278 +/- 75 mm h-1 for aggregation of red cells at 37 degrees C (corrected for plasma viscosity and at constant haematocrit of 30%). Data for subgroups have also been obtained. Linear regressions of apparent blood viscosity against log shear rate were found to be specific to individual racehorses, and differed significantly between some racehorses. Data for blood viscosity, plasma viscosity and haematocrit were near the values reported for human athletes, but rigidity of red cells and aggregation of red cells was found to be much higher in horses. No correlation was found between aggregation of red cells and fibrinogen level. In blood samples from some horses, the erythrocyte sedimentation rates increased with decrease of temperature, while in other samples they increased with increase of temperature. It appears that it is possible to characterise individual horses by blood viscosity factors and viscosity functions.

Animals

Photographic, stereological and statistical methods in evaluation of aggregation of red cells in disease: part I: kinetics of aggregation.

Kinetics of red cells aggregation were studied by microphotography of blood contained between parallel-plates in a slit of 12.5 micrometers. Blood samples, anticoagulated with EDTA, were adjusted to haematocrit of 0.30 using native plasma. Blood was allowed to flow at shear rate of 2000 sec-1, flow was stopped, and sequential photography carried out. Full development of aggregation required from 2 to 10 minutes, depending on the blood sample. Blood studied included normal donors and patients with polycythaemia, lymphoma, hyperparathyroidism, Waldenström's macroglobulinaemia, influenza. The quantitative evaluation of colour slides was carried out on Microvideomat No. 2 with Zeiss Interference Monochromator, using light wave length of 460 or 560 nanometers. The stereological parameters defined included d(Heyn), Lamda, and S/V. Linear regressions of stereological parameters against square root of stasis time showed correlation coefficients of 0.8 up to 0.99. Linear regressions for different blood samples were compared, and significance of differences between slopes or between elevations was defined using F-distribution. Such differences were significant up to P less than 0.001. Rate of aggregation was much higher in macroglobulinaemia or lymphoma than in normals, and it was lowest in the hyperparathyroid disease.

Erythrocyte Aggregation