Influence of moxaverine hydrochloride on membrane curvature and microsieve filterability of red cells after exposure to hyperosmolarity and lactacidosis.

Using a combination of novel techniques to assess quantitatively the shape and the filterability of red blood cells (RBC) after exposure to stress conditions (400 mosmol/l, lactacidosis, pH 6.8), the effects of 1-benzyl-3-ethyl-6,7-dimethoxy-isoquinoline hydrochloride (moxaverine-HCl, Kollateral) were tested. The shape of freely suspended RBC was quantified using the tangent count procedure. The filterability (microrheological performance) of leukocyte-free RBC suspensions was determined by computer-assisted conductometry using novel precision metal microsieves with uniform pore diameter of 4.2 micron. Moxaverine, when present in doses between 10(-5) und 10(-2) mol/l while the RBC are stressed, restored both the normal discoid red cell configuration and the microrheological performance when tested under low shear stresses. The data show that moxaverine, a papaverine derivative, hitherto considered as a classical vasodilator exerts protective effects on RBC membrane curvature and whole cell microrheological behavior (performance). The protective effects manifest themselves when the RBC's are exposed to abnormal biochemical conditions such as they might occur in poststenotic areas, where hypoxic ischemia is known to lead to a combination of hyperosmolarity and lactacidosis which modify the RBCs.

The contribution of haemorheology to the understanding of microcirculatory disorders. An introductory overview.

As a result of continuing advances in methods and instrumentation, our knowledge of the flow behaviour of blood has considerably increased in recent years. At present, however, in an attempt to understand the pathophysiological events occurring within the microcirculation, it does not appear possible to directly extrapolate data and information obtained from ex vivo studies to the in vivo condition. In spite of this, in vitro studies on the flow behaviour of blood are of diagnostic, and possibly prognostic, value, in that they provide a means to assess a 'factor of risk'. Within the framework of experimental and clinical pharmacological studies, haemorheological data may also contribute substantially to a better understanding of the mechanism of action of drugs.

[Hemorheologic effects of ioxaglate: a contribution to an interpretation of the effect of hyperosmolar roentgen contrast media on the fluidity of erythrocytes]. / Hämorheologische Effekte von Ioxaglat: Ein Beitrag zur Deutung der Wirkung hyperosmolarer Röntgenkontrastmittel auf die Fliessfähigkeit von Erythrozyten.

Almen and Aspelin have shown that the use of non-ionic radio contrast media allows the iodine concentration to be increased (which is desirable because of its effect on radio opacity) without a very large increase in osmolarity (which is undesirable because it impairs the fluidity of erythrocytes). This latter effect can also be diminished by reducing the osmolarity of a dimeric contrast medium as has been achieved by incorporating more iodine atoms into the molecule in the case of Ioxaglate (Hexabrix). In various microrheological tests systems, the fluidity of packed red cell suspension, the corrected filtration rate though 5 micron pores and the relative apparent viscosity of blood-contrast media mixtures (1 to 50% concentration) were determined in experiments comparing this compound with Urografin 76 of the same iodine content. In all systems, the former showed fewer rheological effects. In whole blood viscometry, this can be detected only after appropriate corrections for the effects of the two contrast media on hematocrit and plasma viscosity. As there is a more pronounced water shift from the cells to the plasma, Urografin tends to reduce the viscosity of the plasma-contrast media mixture. The concomitant reduction in MCV and hematocrit level tends to conceal the macrorheological influence of strong cell stiffening. This microrheological effect of the dehydrated cells becomes immediately obvious when the viscometric data are corrected for hematocrit value and plasma viscosity effects.

Recent progress in improving data processing in filtration measurements.

Nucleopore filter membranes currently utilized to assess RBC "deformability" do not meet the strict metrological requirements of a measuring gauge. They present different kinds of inhomogeneities introducing an useless information (a background noise) into measurement results and expressed as poor reproducibility. Variance reduction can only be achieved by eliminating aberrant results from a series of parallel measurements made with different membranes. To this end a procedure is proposed to identify aberrant values by an iterative statistical regression analysis of data from filter calibration and measurements on RBC suspensions and to express results as "reduced" initial flow rates for a standard filter resistance.

The Aachen clinical hemorheology test profile: a proposal for the documentation of hemorheological data in clinical medicine.

The recent development of specific methods to measure directly the microrheological determinants of blood fluidity allows to complement or even substitute global measurements of whole blood apparent viscosity or filtrability through sieves containing restricted pores. While such differentiation is mandatory for practical and theoretical reasons, there is the danger of loosing coherence of measurements essential for correlating hemorheology to other sciences. In an attempt to document hemorheological data in a simple yet comprehensive fashion, a test profile for the display of normalized data from subtests on hematocrit, plasma viscosity, red cell "rigidity" and tendency to red cell aggregation is proposed. Using procedures developed in the behavioural sciences, stringend criteria for evaluating the validity, reliability, standardization, economy and usefulness of individual subtests for the blood viscosity determinants and a compounded hemorheology test profile are proposed. There is good evidence that abnormal hemorheological behaviour of red cell plasma mixtures manifest themselves exclusively in situations associated with grossly reduced in vivo driving pressures and thence shear stresses. In these situations, in which a low flow state is caused by general hemodynamic changes, there is a danger that the blood looses its normal fluidity and undergoes a reversible viscidation: We propose the hypothesis that in these situation abnormally blood poses a risk of a flow limitation (and even interruption) by rheological abnormalities described above. The test profile presented has been developed to supply a more valid experimental method for subjecting the above hypothesis to experimental tests in the clinical situation.

The single erythrocyte rigidometer (SER) as a reference for RBC deformability.

The SER allows the "deformability" of individual red blood cells to be quantitated by determining their passage time through a pore (d = 5.8 microns, 1 = 50 microns) under the shear stresses of 1.5 Pa-4 Pa. Using this system, we examined the influence of: 1. cytoplasmic viscosity, 2. membrane viscoelastic properties, 3. area to volume relationship. To change these determinants of RBC-deformability, the cells have been altered with 1. Acetylphenylhydrazine (0.016 mol/l), 2. diamide (0.5 mmol/l), 3. osmotic swelling (200 mosm/l) and osmotic shrinking (480 mosm/l) by suspending the cells in hypo- and hypertonic saline. The passage time has been found to be primarily influenced by changes in cytoplasmic viscosity. The same cells when tested in 4 other systems considered to measure RBC-deformability (filtrometer, packed cell viscometry, rheoscope and ektacytometry) behaved differently.

Specific methods to determine hemorheological parameters.

Procedures developed by Authors to measure erythrocytes aggregation, fluidity and deformability are presented and relevant features discussed.