Capillary blood viscosity in microcirculation.

As known, at the arteriolar level there is the highest resistance to the flow due to the section and to the velocity with an average pressure fall of 50 mmHg (from 85 to 35 mmHg). This resistance is expressed in sec(-1) by the ratio W/2r. This ratio is very high with an average value of 332 sec(-1) and viscosity at this high shear-rate is negligible. At the capillary level the pressure fall is 11.5 mmHg but the vascular resistance W/2r is much lower, on average 32 sec(-1). We can say that if a resistance of 333 sec(-1) corresponds with a pressure fall of 50 mmHg, then a resistance of 32 sec(-1) should correspond with a pressure fall of 4.8 mmHg. The highest pressure fall is due to another kind of resistance which we can define as "Capillary Blood Viscosity" because it depends on the rheological and structural characteristics of the blood. Our instrument reproduces the structure of the capillary district in an experimental model and measures the General Blood Viscosity (GBV) and the Capillary Blood Viscosity (CBV) at the same shear-rate and in particular at the low shear-rate when in non-Newtonian fluids the highest increase in viscosity appears. Consequently, at the capillary, viscosity is dominant with respect to the other geometric and physical resistances. Moreover, the percentage ratio between the GBV and the CBV gives a physical measure of erythrocyte deformability. Knowing viscosity at shear-rate present in the circulatory system, we can obtain the size of RBCs aggregates in the different circulatory districts and their characteristics expressed like "aggregation bond". Changes in CBV are the only possibility in clinical practice to improve the circulatory flow in the capillary district because it is not sure that changes in the arteriolar section can improve the capillary flow or rather open arterio-venous anastomosis. Moreover, in the systemic circulation the aggregate size allows us to point out the phenomenon of cell adhesion because the presence of several receptors involves also the other blood cells. Finally the size and the stability of the RBCs aggregates can modify the endothelial thrombo-resistance.

[Rheologic modifications induced by heparin therapy. Capillary blood viscosity, erythrocyte deformability, aggregation index]. / Modificazioni emoreologiche indotte dalla terapia eparinica. Viscosità ematica capillare, deformabilità eritrocitaria, indice di aggregazione.

BACKGROUND: The most important problem with which doctors have to deal every day in their practice, is occlusive vascular disease, at the basis of which there is commonly a process of thrombosis. For this reason, it is very important to define early the subjects at thrombosis risk and an appropriate therapeutic strategy. METHODS: We considered 13 inpatients at thrombosis risk, c/o sezione di Clinica Medica I, dipartimento di Medicina Interna e Terapia Medica, Università di Pavia, IRCCS Policlinico S. Matteo, and 12 healthy volunteers, between March and June 1998, evaluating age, sex, weight, diseases and ongoing therapy, hemocytological, hemocoagulational and hemorheological tests before and after heparinic therapy. RESULTS: General blood viscosity, measured by the rotational and double-filtration method, presented no significant changes; on the contrary, capillary blood viscosity and erythrocyte deformability, measured by our new double-filtration method, showed respectively an increase and a decrease. CONCLUSIONS: Calcium heparin is the most frequently used antithrombotic drug in thrombotic diseases and their prevention, but its action on the hemorheological profile is not clear. This study showed that it increases erythrocyte aggregation rate and decreases erythrocyte deformability, having a negative effect on the microcirculation.

[Hemorheology in different types of obesity]. / L'emoreologia nei diversi tipi di obesità.

BACKGROUND: Obesity is a symptom of impaired fat metabolism, organs and system of which are: the liver where fat synthesis and oxidation occur and the adipose tissue with a storage function. Obesity in NIDDM, insulism and suprarenalism is due to an increased synthesis in triglycerides and their deposit in fat cells. Aetiologic factors of primitive obesity act on the fat tissue promoting lipogenesis (hypertrophic or hyperplastic action) and/or reducing fat release. METHODS: Thirty-two women suffering from obesity but without cardiovascular pathologies were investigated. Obesity degree and type were defined by the anthropometric method. The following tests were carried out: glycemia, insulinemia, C-peptide in OGTT, tryglicerides, cholesterolemia and cortisolemia. Plasma viscosity (V) and whole blood V were determined with rotational microviscosimeter; erythrocyte V and plasma-erythrocyte V were performed with double filtering method and values expressed in cP. Deformability was calculated as a ratio between viscosities determined with both filtering methods. RESULTS: On the basis of the type of obesity three groups were characterized: gynoid, intermediate and android. Rheological parameters are increased in all women: increase of plasmatic V, increase especially of erythrocytic viscosity with a considerable decrease in deformability. There are interesting differences among the three groups. CONCLUSIONS: The relationship between obesity and cardiovascular disease is well known and the early rheological impairment could be the factor linking both pathologies. Some factors involved in obesity, such as hyperglycemia and hyperinsulinemia, are also suspected of impairing hemorheology promoting changes in the microcirculation.

[Hemorheologic assessment in hypoxic and hypoxic-hypercapnic states]. / Valutazioni emoreologiche in condizioni ipossiche e ipossico-ipercapniche.

METHODS: Twenty-four male and female people have been examined. They were afflicted with respiratory failure; on blood gas analysis they have been divided into two groups: hypoxic and hypoxic-hypercapnic subjects, disregarding the base pathology. We have used both the rotatory and double filtration methods, using a constant 15 cm water filtration pressure. The following rheological values have been defined: plasmo-erythrocytic viscosity, plasmatic viscosity, erythrocytic viscosity and erythrocytic deformability. The values have been expressed in cP. We have also considered haemacytometric parameters. RESULTS: It came out that all the rheological parameters were highly different in both groups, with an increase of, more or less, 30% in plasmo-erythrocytic viscosity; a four times increase of erythrocytic viscosity compared to normal values and a decrease of 60% in erythrocytic deformability. The plasmatic viscosity was also very increased: we must correlate this phenomenon with phlogotic or neoplastic pulmonary pathology of the people we have examined. Regarding haemacytometric parameters, from the hypoxic-hypercapnic group comes out significant higher MCV values and MCHC lower ones, with a higher anisocytosis level. CONCLUSIONS: From these results we think that the altered systemic rheology makes hypoxic condition wider, while, at pulmonary level, help the haemodynamic resistances to increase, with the onset of a hypertensive condition.

[Blood rheology and fibrinogenemia: two independent parameters in the assessment of cerebral vascular damage]. / Emoreologia e fibrinogenemia: due parametri indipendenti nella valutazione del danno vascolare cerebrale.

The increase in fibrinogen level is consequent on several hurtful events: inflammatory, traumatic, stress reaction. Traumatic event, during cerebral vasculopathies, often causes an inflammatory reaction, certainly in the acute phase, inducing fibrinogen synthesis. There are also other inflammatory changes as the increase in WBC and PLT counts and in other hematic components, both in increase and in decrease. Patients with cerebral vasculopathies were divided in two groups according to the clinic picture seriousness. Haemorheologic characteristics were measured with a double filtering method I (with 5 and 12 mu filters) and under a filtering pressure of 15 cm H2O, eliminating WBC interference even if using native blood. In this way we have determined whole blood, plasma, and plasma-erythrocyte viscosities. From these measures we have obtained corpuscular viscosity and erythrocyte deformability. Fibrinogen concentration is increased in all patients with acute vasculopathies, but there is not a difference in relation to the clinic pictures seriousness. Also other inflammatory parameters, namely: total protein, gamma-globulins, ESR, are increased in a significant way without difference in relation the clinic seriousness. The WBC count is more increased in the group with Stroke than in the other one with TIA. The corpuscular viscosity is almost doubled with consequent decrease in deformability; plasma-erythrocyte viscosity, measured with both methods, is quite increased. These parameters show the same behaviour in both groups. Only plasma viscosity increased in the group with Stroke. Haemorheology alteration is not statistically correlated to the fibrinogen level. The decrease in deformability can be related to the viscouselastic membrane properties, and the fibrinogen, because of its adhesive properties, can contribute to such a decrease.

[Relationship between hemorheology and pro- and anti-coagulation factors in inflammatory and degenerative vascular diseases]. / Rapporto tra emoreologia e fattori pro- ed anti-coagulanti nelle vasculopatie infiammatorie e degenerative.

After having found out an increase in the Von Willebrand Factor (vWF) and a relation between its persistance and seriousness of some vasculities, we looked for a link between changes in vWF level and hemorheology, their role and interdependence in the evolution of the vascular diseases, in complications and in relapses. We studied patients affected with degenerative and inflammatory vascular diseases and we determined rheologic parameters, in traditional and personal innovative way, pro- and anti-coagulation factors, other inflammatory proteins and hematic parameters. As regards coagulation only the vWF appeared increased in a significant way, without differences between two types of vascular diseases. As regards hemorheology, in both of them we measured an increase in the whole blood viscosity but with a different behaviour of its components. In the degenerative vascular diseases there was an increase both in corpuscular viscosity and in the plasma-erythrocyte one, a no significant increase in the plasma viscosity whereas the erythrocyte deformability was in the normal range. In vasculitis there was the highest increase in the plasma and corpuscular viscosities with a decrease in the deformability without changes in the plasma-erythrocyte viscosity. We give some interpretations on their different behaviour and a right meaning of the involved phenomena in every kind of rheologic parameter.

[Factor VIII/Ag (von Willebrand) and protein C. Erythrocyte deformability and aggregability. The risk parameters of retinal vein occlusion]. / Fattore VIII/Ag (von Willebrand) e proteina C. Deformabilità e aggregabilità eritrocitaria. Parametri di rischio di occlusione venosa retinica.

In 32 patients with retinal vein occlusion we measured coagulative and hematic parameters. The coagulative factors were in the normal range, save C-Protein, that was decreased and the Von Willebrand Factor that appeared increased in a significant way. These changes do not affect the coagulation state, but, in a local vascular district, they can interfere with mechanisms of thromboresistance, over all in the retinal district owing to its peculiar structure and its flow of terminal kind. The hemorheologic alterations consist in a decrease in the erythrocyte deformability and in an increase in the plasma-erythrocyte and plasma viscosities, measured both with a rotational method and with a filtering one. We have not found any correlation between coagulative factors and hemorheologic parameters, nevertheless these last ones determine a lowering down of the local flow, that with the morphological changes in the vascular system, give rise to conditions for an occlusion event.

[Rheologic features of erythrocytes in beta-thalassemia minor]. / Caratteristiche emoreologiche del globulo rosso nelle beta-talassemie minori.

The study assessed the physical characteristics of erythrocytes, viscosity and deformability, measured by a widely described double-filtration method. At the same plasma-cell viscosity was measured and the importance of the rigidity of RBC was evaluated as one of the many forces which interact among the cells and between the plasma and cells. The results showed a marked increase in corpuscular viscosity with reduced deformability, and a significant diminution of plasma-erythrocytic viscosity, whereas total viscosity remained unaltered. These parameters do not correlate with the quantitative pathological alterations of HbA2, but only with RDW-SD. Alterations of the proteic components with a relative increase in the alpha-chains of the erythrocytic membrane are thought to be responsible for these anomalies, by means af the modifications that the excess of alpha-globin causes to the structure and function of erythrocytic membrane; but the quantity of globin is not the decisive factor, and in fact the introduction of the beta-chains are able to correct erythrocytic deformability (Sorensen). Membrane rigidity is probably independent and unrelated to microcytemia, because these erythrocytes, have an excess of surface in relation to their volume, due to the simultaneous alteration of permeability. The diminished plasma-erythrocytic viscosity should be connected with the prevalence of repulsing forces, due to erythrocytic rigidity in relation to the attracting forces due to the proteic fractions which remain unchanged.

[Plasma-erythrocyte viscosity and evaluation of several pro- and anti-aggregating factors in NIDDM patients in metabolic decompensation state]. / Viscosità plasmaeritrocitaria e valutazione di alcuni fattori pro-aggreganti ed anti-aggreganti nei diabetici NID in stato di scompenso metabolico.

In NIDDM diabetic subjects, the microcirculatory damage shows a double aspect: an alteration of the vascular wall, particularly of the arteriolar capillary, and a hemorheological alteration at the level of the capillary district. In the microcirculation, because of the low velocity of the flow and the inverse relationship between capillary size and RBC diameter, the viscosity has an important role with its components: RBC viscosity and deformability. Even the erythrocyte aggregation has a key role as resultant of the attracting and repulsing forces, among which the plasma-RBC viscosity and the deformability play opposite role. Our method allows to evaluate the erythrocyte, the whole blood, the plasma and the plasma-RBC viscosity, and the deformability. Studies from this laboratory in NIDDM subjects show an increase in the blood viscosity, a decrease in the erythrocyte deformability and plasma-RBC viscosity. It is suggested that in microcirculatory district the flow reductions are particularly of hemorheological type and that the sludged blood is an "optical" phenomenon with poor meaning. We consider some hematological parameters, namely the Hgb A1c %, Hgb concentration, RBC count, MCV, etcetera.

[Relations between plasma-erythrocyte viscosity factors and ESR]. / Rapporto fra fattori viscosi plasmaeritrocitari e VES.

The ESR is usually put in relationship: to the real density of the RBCs (erythrocytes) (difference between the RBC specific gravity and the plasma one), and to the resistance that the RBCs meet moving in a medium, which is due to the plasma viscosity and to the total external RBC surface. When the RBCs take shape of aggregates, their external surface is decreased and ESR increases. The most important plasma factor causing changes in ESR is the fibrinogen level followed by the plasma globulins and by the products arising from the tissue damage. The resistance that the RBCs meet moving in the plasma is well expressed by the measurement of the plasma-RBC viscosity considering that is inclusive of both factors that are the plasma viscosity and the external RBC surface. The plasma-RBC viscosity is the resultant of several factors: Fa = Fb - Fe - Fs - Fm, were: Fa is the resultant, Fb the attracting forces due to the proteic macromolecules, Fe the repulsing forces due the negative charges. Fs the repulsing forces due to the shear-stress, Fm the force which opposes itself against the surface tension of the aggregation; it depends on the RBC morphology and on the RBC rigidity. The ESR has been recently used like an index of the RBC aggregation. The Authors study the relationship between several hemorheological parameters and the ESR in infective and inflammatory processes.(ABSTRACT TRUNCATED AT 250 WORDS)

[Model of therapeutic programming in NIDDM diabetes]. / Modello di programmazione terapeutica nel diabete NIDDM.

The usual choice of therapy in NIDDM diabetes, using oral anti-diabetic compounds, insulin or associated treatments, is based on the results of treatment evaluated empirically using glycemic profiles. As a contribution to the search for a method of choosing a treatment which is based on laboratory data and can restore metabolic equilibrium as quickly as possible using the most efficacious drug at an optimal dose, the paper reports a method of assessing the severity of diabetes according to mean daily glucose concentrations, the degree of instability in relation to the standard deviation, and proposes a sensitivity test to SU which indicates the choice of therapy, together with an insulin sensitivity test which is useful for evaluated the optimal dose. Sensitivity to SU evaluated using this method is not dependent on the degree of severity of diabetes. With regard to its practical use for prescribing treatment the test is highly predictive in positive cases since it is extremely sensitive, while its low specificity does not rule out its use in cases of resistance. The analysis of the results obtained after treatment which was not indicated by the sensitivity tests but based on personal experience and the comparison of the two methods shows that a high percentage of patients received inadequate therapy either due to the prescription of the wrong type of treatment or an incorrect dosage.

[Indications and methods of treatment with sulfonylureas in NIDDM patients]. / Indicazioni e modalità nel trattamento con sulfaniluree nei diabetici NIDDM.

Metabolic corrections induced by SU therapy can be assessed by daily glycemic changes which reflect all metabolic events taking place during the 24-hour period. Varying responses to treatment reveal different degrees of metabolic reserve. In order to be meaningful the SU sensitivity test must be compared to the daily glycemic profile. Sensitivity test responses were first compared to similar alterations following treatment; and secondly, the correlation was determined between the sensitivity test and the daily percentage of glycemic decrement induced by therapy. The high significance of these comparisons confirmed that the SU sensitivity test is a reliable index of response to treatment and this has also influenced treatment methods. When studying the modes of action of the SU sensitivity test we took into account insulin incretion and sensitivity tests to exogenous insulin to determine the level of receptor activity. Even during acute treatment, SU action is mediated by insulin incretion, whereas SU activity is not related to changes in the receptor system induced by exogenous insulin stimulation.

[Erythrocyte viscosity-deformability-aggregation. A clinical reality]. / Viscosità-deformabilità-aggregazione eritrocitaria. Una realtà clinica.

Current clinical practice and indications for drug therapy for vascular pathologies of different etiology reveal the need to measure blood viscosity, either on the spot or at the site of greatest impact. The Authors propose as easily performed method of calculation using Reid's well-known technique, which, based on the measurement of hematic filterability using filters with different sized pores, gives the viscosity of the various fractions which make up overall viscosity but which have a different impact on areas of the circulation and their functions: total blood viscosity, corpuscolar viscosity, plasma-erythrocytic viscosity. These are quantified in cP as a values which is independent of the degree of sanguification and are markers of a functional flow datum. Erythrocytic deformability, expressed as a percentage of the inverse viscous impact of red cells on total blood viscosity, is restricted to a narrow range in the control population, and is therefore a very reliable parameter for the assessment of pathological and pharmacological changes. In addition to normal values, changes in subjects suffering from thalassemia are used as a paradigmatic example of structural and morphological erythrocytic changes without other associated diseases. A model table illustrates the methods of calculation used to obtain the degree of filtration in cP from filtration data.

[Intraerythrocyte folates and leukocytic neutrophil segmentation in macrocytosis in patients with liver disease]. / Folati intraeritrocitari e segmentazione leucocitaria neutrofila nella macrocitosi dell'epatopatico.

The problem of macrocytosis above all concerns deficiences and the study of these aspects is particularly important in hepatopathic patients for therapeutic purposes. A state of deficiency can also be revealed in morphological terms by the assessment of the hypersegmentation of polymorphonucleate neutrophil leucocytes. In the group of hepatopathic patients included in the study there was no significant differences in vitamin B12 concentrations in comparison to normal values, whereas mean levels of serum folates were decreased, although still within the normal range. It is worth underlining that to evaluate vitamin B12 it is necessary to measure analogous inefficient components from a metabolic point of view and the assessment of serum folates is not important as an index of normal erythropoietic activity. To overcome this limitation, we assayed intraerythrocytic folates which are vitamin-B12-dependent and these too proved to be within the normal range. Leucocyte hypersegmentation was also excluded by evaluating the mean of PMN lobes. A clearly normal RDW was also observed in macrocytic anemia in hepatopathic patients and this may represent a further difference from hepatocytic macrocytosis.

[Sulfonylurea resistance in type II diabetes mellitus. Assessment of metabolic and hormonal aspects]. / Resistenza alle sulfaniluree nel diabete di tipo II. Valutazione degli aspetti metabolici ed ormonali.

Sensitivity tests to SU allow two populations to be distinguished. One contains severely diabetic subjects in a continuous state of metabolic precariousness with reduced alkaline reserves, hyperinsulinemia and insulin resistance; the other contains mildly diabetic subjects who are normoinsulemic and show no insulin-resistance to i.v. tests irrespective of the presence of a similar level of SU resistance. While the first group may be more readily interpreted, especially with reference to the dualism between the alterations of insulin synthesis and resistance of peripheral tissues, with special reference to the function of receptors and post-receptors, the second group raises numerous questions of interpretation. The test becomes important to identify those subjects who right from the start show a reduced insulin secretion to drug stimulation and the possibility of obtaining euglycemia with high doses of SU. This finding suggests the existence of a genetically determined mechanism for SU resistance: in addition to the population who show marked SU resistance from the onset of diabetic symptoms, there is also a group of subjects in whom this resistance is less evident and may be provoked only by certain stimuli or spontaneously under stress, or by the appearance of the triggering metabolic factor. It is clearly important to identify the latter population before the clinical manifestation of symptoms so as to establish the correct therapy or combined therapy. This led us to consider the SU-resistant cases in the series of patients studied as being two clinical stages of the same condition rather than two separate populations with different pathogenesis.

Beneficial effect of prolonged total parenteral nutrition in a very malnourished cystic fibrosis patients.

A very malnourished Cystic Fibrosis (CF) patient was treated with integrative Parenteral Nutrition (PN). With a mean caloric supplementation of 2,550 Kcal/day a weight gain of 6.5 Kg was achieved. In spite of severe pulmonary complications (pneumotorax and pneumomediastinum), pO2 increased from 53 to 72 mmHg and pCO2 from 38 to 56 mm Hg. General conditions improved, appetite was restored and the patient cleared off continuous oxygen therapy; he left the hospital and did not present any more pulmonary exacerbations. In the following 8-month period he maintained a daily caloric intake of 80 Kcal/kg with a further weight gain of 4.5 Kg.

[Presentation of a method of interpreting erythrocyte deformability]. / Presentazione di un metodo di interpretazione della deformabilità eritrocitaria.

The physical principles of a method based on a haematic double filtration, according to Reid classic technique is explained. The aim is to determine a method for researching the characteristics of erythrocytic deformability, without changing the original medium, exoerythrocytic essential component of the membrane physiochemical quality and intraerythrocytic for the fast, active exchanges, after an evaluation of different techniques and instrumentation. A practical example for calculating the factor of correction, with reference to personal material, is made. This method has the advantage that it does not need the manipulation of the sample and does not delay the determination.

[Hemorheology and acute in vivo changes in non-viscous serum factors]. / Emoreologia e variazioni acute "in vivo" di fattori sierici non viscosi.

During research into a real model permitting study of the rheological effect of serum constituents without viscous power, the viscous features of blood and plasma and erythrocyte deformability and aggregability were evaluated before and after dialysis in relation to variables acutely modified by therapy. Interdependence with certain serum factors often considered responsible for rheological changes in various pathologies after maximum alteration and, in the short term in the same subject, under normal conditions were controlled.

[Hemorheologic, metabolic and blood coagulation changes in diabetics in treatment with sulfanyl ureas]. / Modificazioni emoreologiche, metaboliche ed emocoagulative in diabetici in trattamento con sulfaniluree.

A study was carried out to see if chronic treatment with a sulphanylurea with hypoglycaemic action, with also haemoactive action in terms of anti-platelet aggregation, profibrinolytic and antifibrinogenetic action also acted haemorheologically. For this purpose a group of patients treated with Gliclazide was compared with a group under treatment with Glibenclamide. A significant variation was noted in terms of an increase in erythrocyte filtrability and a diminution in erythrocyte aggregation with diminution in blood viscosity at low shear-rates. The absence of parallel modifications in quantitative corpuscular viscous factors, the early onset of the process, the real diminution in the sense of a reduction below the range of normality suggests that the effect is pharmacological and not mediated by metabolic compensation.

[Macrocytosis in relation to the severity of the hepatopathy]. / Macrocitosi in rapporto alla gravità dell'epatopatia.

Among factors causing the hepatopath's relative erythrocyte macrocytosis, the influence of alcohol and liver function damage was compared. Hepatopathic macrocytosis is different from Biermer's macrocytosis and evidently involves different pathogenetic mechanisms. It is significant that a deficit in vit. B12 does not occur and a modest deficit in folates only rarely. There is much evidence of an alteration in lipidemia and particularly in apo-protein content. It is concluded that the two factors considered have different mechanisms but produce the same results.