Hemodynamic and hemorheologic effects of i.v. Dilevalol in hypertensive patients.

The authors evaluated the effect of Dilevalol infusion on blood pressure, heart rate, central hemodynamics, and rheologic parameters in hospitalized inpatients affected with mild or moderate hypertension. After a dose-finding phase and a washout period of one week, 10 patients aged fifty to seventy-two-years (median 61.5) were given either a single dose of Dilevalol 60 mg or placebo, and seven days later they underwent the other treatment, according to a single-blind, crossover design. Central hemodynamic measurements were performed by means of M-mode echocardiography, and hemorheologic parameters were evaluated by means of strain-gauge plethysmography. The maximal increase in lower extremity flow at rest had been obtained with the infusion of 60 mg Dilevalol during dose-finding, and so this dose was chosen for the second part of the study. The infusion of Dilevalol significantly increased rest flow and decreased blood viscosity, but the changes in central, parameters were not considered clinically relevant, although statistically significant. Blood pressure decreased without significant changes in heart rate. Thus, the acute administration of Dilevalol reduced blood pressure, without affecting heart rate and central hemodynamics, confirming the vasodilating effect of the drug. A significant improvement was also shown on blood viscosity in these hypertensive patients.

[The effects of vinburnine on the blood rheology parameters and on the oxyhemoglobin dissociation curve and 2,3-diphosphoglycerate. In vitro research]. / Effetti della vinburnina sui parametri emoreologici e sulla curva di dissociazione ossiemoglobinica e 2-3 difosfoglicerato. Ricerche in vitro.

The authors investigate the protective action of vinburnine on impairment of blood haemorheology and on metabolic parameters due to in vitro ageing of blood samples. In each sample the following parameters were measured: blood viscosity and filterability, p50 and 2,3-DPG. Vinburnine is able to induce a slight improvement of haemorheological parameters and of p50 compared to controls. After incubation for 4 hr, a reduced impairment of the mentioned parameters was observed in comparison with controls. Some hypotheses are discussed about the mechanisms of action of the drug.

[The effects of the acute administration of vinburnine on blood rheology, oxygen transport and regional circulation under normal conditions and in hypoxemia. In vivo research]. / Effetti della somministrazione acuta di vinburnina sulla reologia ematica, trasporto dell'ossigeno e sulla circolazione distrettuale in condizioni normali e di ipossiemia. Richerche in vivo.

Vinburnine has been shown to be effective in avoiding chronic ischaemic tissue injury. Many studies have demonstrated the antihypoxic and oxygenation properties of this drug. In our study we have evaluated in two groups of patients the effects on blood rheology, oxygen transport, regional circulation and ergospirometric data of 40 mg vinburnine infused in a systemic vein. We have selected in the first group 10 patients with low hemoglobin oxygen affinity (p50 28.6 +/- 1.37 mmHg), in the second one 7 patients with normal values (p50 26.6 +/- 0.84 mmHg). In the two groups of the study we evaluated nutritional blood flow by a plethysmographic method, blood gas analysis [correction of hemogasanalitic] parameters in arterial and venous blood, haemoglobin oxygen affinity expressed as p50 and erythrocytic 2,3-DPG, hemorheologic and ergospirometric parameters. Data were evaluated in basal conditions and at the end of the infusion. The improvement of rheological properties, hemodynamic and metabolic data in the two groups of the study seems to confirm the oxyphoretic properties of this drug.

[Calcium dobesilate, hemorheology, fibrinolysis and endothelium. New perspectives on the prevention of diabetic microangiopathy. Clinical pharmacological study]. / Dobesilato di calcio, emoreologia, fibrinolisi ed endotelio. Nuove prospettive nella prevenzione della microangiopatia diabetica. Studio di farmacologia clinica.

The authors report the results of a double-blind cross-over study on calcium dobesilate in which two groups of eight recent-onset type-II diabetics were treated either p.o. (1 g once daily) or i.v. (500 mg in 100 ml of physiological saline) with calcium dobesilate or with placebo. During oral administration of the drug, blood rheology and total fibrinolytic capacity were assessed by calculating euglobulin lysis time. In view of the evidence for a viscosity-lowering action of the drug (which had already been found in "long-term" studies) and of potentiation of fibrinolytic activity, intravenous treatment was started with the object of elucidating the possible mechanisms of action, evaluating at the same time other parameters concerning the functional fibrinolytic pathways. It has thus been possible to ascertain that the drug has "rheologic" activity, interferes with the function of endothelial cells by stimulating the release of tissue plasminogen activator and thus increases fibrinolytic activity while not interfering with the clotting function and not altering platelet beta-thromboglobulin secretion. These findings appear to confirm the possibilities for therapeutic use of calcium dobesilate which is thought to act on a variety of pathogenetic mechanisms involved in diabetic microangiopathy.

Allopurinol prevents ischaemia-dependent haemorheological changes.

Pre-treatment with allopurinol is able markedly to attenuate the deterioration in blood viscosity (BV) and whole blood filterability (WBF) that occurs after ischaemia during exercise. It also reduces the exercise-induced increase in serum oxidase activity, although this action is slightly less effective in peripheral obliterative arterial disease (POAD) patients. Conversely, allopurinol is completely ineffective in modifying haemorheological parameters in vitro, and it does not affect superoxide anion generation or enzyme release from neutrophils stimulated in vitro with formyl-methionyl-leucyl-phenylalanine (FMLP). It is suggested that allopurinol may attenuate changes in BV and WBF by affecting xanthine-oxidase-dependent free radical formation in tissues.

Primary and secondary blood hyperviscosity syndromes, and syndromes associated with blood hyperviscosity.

Despite the methodological difficulties of evaluating the role of a single rheological component, some clinical situations characterised by an increase of blood viscosity can be identified. These are classified as 'blood hyperviscosity syndromes' and can be divided into 2 groups. The first includes pathophysiological conditions in which a primary blood abnormality causes a decrease of blood flow, as occurs in polycythaemic, sclerocythaemic and seric hyperviscosity syndromes, and may be referred to as 'primary blood hyperviscosity syndromes'. The second group includes pathological conditions in which a primary reduction of blood supply to tissue provokes tissue ischaemia, and an impairment of rheological properties of blood can be observed at microcirculatory level. Thus, these situations have been described as 'secondary blood hyperviscosity syndromes'. Patients with peripheral obliterative arterial disease, ischaemic cardiopathies and cerebrovascular insufficiencies show a diminution in blood fluidity during spontaneous or provoked ischaemic conditions which disappears after reperfusion of the tissue. The pathogenesis of this rheological damage is unclear, but may arise from the complex relationship among blood cells (red cells, leucocytes, platelets), endothelium and plasma components. In addition to these 2 groups of blood hyperviscosity syndromes, several pathological states such as diabetes, shock, surgery, and rheumatic disease have been described in which an increase of blood viscosity can be observed. For these situations, which require much further investigation, the term 'syndromes associated with blood hyperviscosity' could be proposed.

Hemorheological factors in the pathophysiology of acute and chronic cerebrovascular disease.

The hemorheologic changes in three groups of patients suffering from acute and chronic cerebrovascular diseases were studied. Firstly, a horizontal study on 57 patients with definite stroke and on 49 patients with TIA was made. Plasma viscosity, whole blood filtration rate, fibrinogen concentration and hematocrit were evaluated as markers of the rheological property of blood. Blood samples were drawn within 6 h from the onset of vascular syndrome. The findings were compared with values obtained in 112 as controls. At the same time, washed red cell filtration rate, together with lactoferrin, betaglucuronidase and beta-thromboglobulin plasma level were assayed. In both groups the onset of the vascular storm was associated with a marked increase of plasma fibrinogen and of blood and plasma viscosity and a significant decrease of whole blood filterability. Lactoferrin, betaglucuronidase and beta-thromboglobulin levels were also significantly increased. Following this, a longitudinal study was performed on 27 patients with definite stroke and 32 patients with TIA. The clinical regression of acute stroke was associated with the progressive reduction of rheological abnormalities. Finally, 81 patients with clinical diagnosis of cerebrovascular disease due to previous stroke or repeated TIA were studied together. An increase of blood viscosity, of fibrinogen concentration and of hematocrit and a decrease of blood filtration rate together with higher levels of beta-thromboglobulin were registered. These results confirm the existence of an association between CVD and hemorheological alterations and suggest more in depth research directed towards identifying the significance of these alterations in the pathogenesis of tissue ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)

[Assay of erythrocyte ATP by chemoluminescence. Protective action induced by pentoxifylline on the depletion of energy from stored erythrocytes]. / Valutazione dell'ATP eritrocitario per chemiluminescenza. Azione protettiva indotta dalla pentossifillina sulla deplezione energetica da conservazione delle emazie.

A new method to measure erythrocyte ATP levels is used. The authors have incubated 6 whole blood samples and 7 samples containing washed red blood cells for 6 h. They measured ATP levels and confirmed an important decrease of the values during the time. If the same samples were incubated with pentoxifylline (1.4 X 10(-4) M), the ATP decrease was less relevant.

[A syllectrometric method to study erythrocyte aggregation]. / Considerazioni su una metodica sillectometrica per lo studio dell'aggregabilità eritrocitaria.

The authors show a new method to study erythrocyte aggregation; the results of in vitro study, obtained by modification of several parameters (hematocrit, immunoglobulins, fibrinogen concentrations), are exposed. The authors did not find in vivo correlations between MAE and hemorheological parameters in different diseases; they found low MAE values only in myelomatous subjects. Adding erythrocytes from healthy donors to myelomatous plasma and vice versa, they found low MAE values only in samples containing erythrocytes and plasma from myeloma. These results suggest that many factors, not only erythrocyte aggregability, contribute to determine MAE (Mean Aggregation Entity).

[Hemorrheological changes in ischemic heart disease]. / Le alterazioni emoreologiche della cardiopatia ischemica.

Ischemic cardiopathy in its various clinical manifestations, whether acute (angina pectoris or myocardial infarction) or chronic (chronic coronary insufficiency), has shown in recent years particular hemorheological characteristics of its own. The observation of patients with such diseases has allowed us to record the existence of modifications in the parameters indicative of rheological damage. Numerous studies have been made, many of which are still in progress, with the aim of clarifying the relationships between these data and the disease. In our experience an increase in blood and plasma viscosity and a decrease in red cell deformability are often present in a manner which is statistically significant, if these patients are compared with normal subjects. Hemorheological change is more evident in the acute forms of myocardial ischemia. In fact, in angina pectoris the occurrence of pain is always accompanied by an increase in blood viscosity and by a worsening of red cell deformability both during spontaneous crises and during provocative tests. The hemorheological damage tends to diminish fairly rapidly when the crisis is over, even if the level of stabilization proves to be still higher than normal. In myocardial infarction higher levels of viscosity appear for a brief period after the onset with a slight tendency to diminish up until the 30th day. With the aim of ascertaining whether the alteration is more evident precisely at the point where the ischemia occurs, we chose a necessarily limited number of subjects, undergoing coronarography and atrial pacing for diagnostic purposes, and decided to control the hemorheological data not only in the systemic venous blood but also in the blood taken from the coronary sinus. Our data has shown that the level of viscosity and of red cell filtrability, in the blood taken from the coronary sinus, is worse than those of the systemic venous blood and that, after atrial pacing, in negative pacing subjects the variations are of slight significance whilst in positive pacing subjects we observe a rapid increase in viscosity and a decrease in red cell filtrability. This seems to confirm what we have already observed in the limbs affected by peripheral ischemia, and to demonstrate the existence of a local hyperviscosity syndrome which, even in the myocardium, appears to be dependent on the tissue ischemia.

[Methodological survey of whole blood filtration in the evaluation of erythrocyte deformability. I. Effect of temperature]. / Rilievi metodologici sulla filtrazione del sangue intero nella valutazione della deformabilità eritrocitaria. I. Effetto della temperatura.

We have demonstrated how temperature affects whole blood filterability. The filtration index appears to be dependent on temperature; the higher temperature is, the higher it rises. At body temperature of 37 degrees C the method resulted more reliable.

[Methodological survey of whole blood filtration in the evaluation of erythrocyte deformability. II. Effect of preservation time at various temperatures]. / Rilievi metodologici sulla filtrazione del sangue intero nella valutazione della deformabilità eritrocitaria. II. Effetto del tempo di conservazione a varie temperature.

We have demonstrated how conservation time affects whole blood filterability. The filtration index decay appears just after withdrawal and is present, with different characteristics, both at room temperature and at 37 or 4 degrees C. It is absolutely necessary to take measurements immediately after blood withdrawal.

[Methodological survey of whole blood filtration in the evaluation of erythrocyte deformability. III. Relative influence of various cellular components]. / Rilievi metodologici sulla filtrazione del sangue intero nella valutazione delle deformabilità eritrocitaria. III. Influenza relativa della diverse componenti cellulari.

We have counted the different types of blood cells before and immediately after filtration. During filtration, an almost equal quantity of each type of cells remained in the filter, with a slightly higher percentage of leucocytes. The problem regarding occlusion of filter pores should be considered in the light of these findings.

[The relation between erythrocyte filterability and platelet aggregation (in vitro studies in normal subjects and those with vascular disease before and after isotonic exercise)]. / Studio di alcuni aspetti dei rapporti fra filtrabilità eritrocitaria ed aggregazione piastrinica (ricerche in vitro in soggetti normali e vasculopatici prima e dopo sforzo isotonico).

The aim of this study was to evaluate the possible action in vitro of the platelets on the rheological behavior of red blood cells in healthy subjects and in patients with peripheral obliterative arterial disease before and after an isotonic exercise. Red blood cells and platelets from control subjects and from patients were tested in several ratios before and after the exercise studying the erythrocyte filterability. beta-thromboglobulin, a platelet-specific protein, was determined in vivo in all subjects before and after the exercise and in vitro as percent of increase between PPP and PRP activated, to monitor the platelet release. The results showed the interrelationship between platelet activation and rheological behavior of red blood cells.

[The effect of lysine acetylsalicylate on hemorrheological changes induced through ischemic exertion in patients with vascular disease]. / Azione dell'acetilsalicilato di lisina sulle alterazioni emoreologiche indotte dallo sforzo ischemico in pazienti vasculopatici.

This study has been performed to evaluate the in vivo effect of acetylsalicylic acid (ASA) i.v. infusion at two different dosages: 500 and 2,000 mg on the main hemorheological parameters (blood viscosity and filtrability, hematocrit) and on beta-thromboglobulin (a platelet-specific protein) in patients with peripheral obliterative arterial disease, before and after an ischemic exercise. The results obtained before and 3 and 24 h after the drug administration induced us to think that platelet-specific substances released during the ischemic exercise can affect the hemorheological parameters and that ASA may be able to interfere with these reactions by inhibiting the platelet release.