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The aim of this study was to compare the cardioprotective effects of salvianolic acid B (Sal B) and the angiotension-converting enzyme inhibitor, benazepril, in rats with chronic myocardial infarction (MI) that resulted from a coronary artery ligation for 4 weeks. The rats were divided into four groups: those undergoing a sham operation; a MI group; a MI+SalB group (100 mg/kg by a gavage, once a day for 4 weeks); a MI+benazepril group (10 mg/kg by a gavage, once a day for 4 weeks). The following parameters were measured: echocardiographic, hemodynamic and hemorheological changes, angiogenesis, infarct size and cardiac remodeling and the messenger ribonucleic acid (mRNA) of vascular endothelium growth factor (VEGF). Rats treated with SalB or benazepril manifested the following: (1) marked improvements in echocardiographic, hemodynamic and hemorheological parameters; (2) significant reduction of infarct size; (3) significantly attenuated heart, kidney and lung hypertrophies, left ventricular (LV) dilatation and fibrosis. The unique effects of SalB were angiogenesis and augmented VEGF expression in the border and remote noninfarcted left ventricular area. These results suggest that both SalB and benazepril exerted beneficial cardioprotective effects in our experimental system, but that the modality of Sal B was different from that of benazepril. The additional beneficial effects of Sal B relative to benazpril, augmenting VEGF expression and promoting angiogenesis, may result in improved myocardial microcirculation.

It has been shown that benidipine, a long-lasting calcium (Ca) channel blocker, may exert its protective effect against vascular disorders by increasing nitric oxide (NO) production. The purpose of the present study was to investigate whether orally administered benidipine might influence the membrane function in patients with essential hypertension. We measured the membrane fluidity of erythrocytes by using an electron paramagnetic resonance (EPR) and spin-labeling method. In the preliminary study using erythrocytes obtained from healthy volunteers, benidipine decreased the order parameter (S) for 5-nitroxide stearate (5-NS) and the peak height ratio (ho/h-1) for 16-NS in the EPR spectra in vitro. The finding indicated that benidipine increased the membrane fluidity and improved the microviscosity of erythrocytes. In addition, it was demonstrated that the effect of benidipine on membrane fluidity of erythrocytes was significantly potentiated by the NO-substrate, L-arginine. In the separate series of the study, we observed that orally administered benidipine for 4 weeks significantly increased the membrane fluidity of erythrocytes with a concomitant increase in plasma NO metabolite levels in hypertensive subjects. The results of the present study demonstrated that benidipine might increase the membrane fluidity and improve the microviscosity of erythrocytes both in vitro and in vivo, to some extent, by the NO-dependent mechanism. Furthermore, it is strongly suggested that orally administered benidipine might have a beneficial effect on the rheologic behavior of erythrocytes and the improvement of the microcirculation in hypertensive subjects.

Report on therapeutic procedures in patients with second and third degree congelations (frostbite) on the feet. Two mechanisms of tissue damage caused by exposure to cold temperature will be discussed pathophysiologically: direct freezing injuries and cell death through intra and extracellular ice crystal formation as well as transient and finally irreversible tissue damage due to decreased perfusion. The condition of decreased perfusion results from persistent vaso-constriction induced by cold temperature, increased blood viscosity, sludge phenomenon and occlusion by platelet thrombi in the microvasculature. Frostbite beyond the erythematous stage should be treated primarily with a parenteral therapy in order to improve the hemorrheologic parameters, in particular within the micro-vascular compartment. Colloidal plasma volume expander such as 10% dextran solution is used to increase the intravascular volume. This solution (with its coating effect) and pentoxifyllin lowers the aggregation of erythrocytes and platelets. The latter will also be favourably influenced by the use of iloprost or acetylsalicylic acid. Iloprost as a stable metabolite of prostacyclin is a powerful vasodilator which attenuates the peripheral vascular resistance and activates fribrinolysis. Pentoxifyllin is considered to lower pathologically increased levels of fibrinogen. Both drugs may protect against damage of the vascular endothelium. Based on their pharmacological effects the above-mentioned drugs may improve tissue perfusion and therefore tissue damage caused by frostbite can be limited. However, an important factor is to strictly avoid bacterial infections in the cold-damaged tissue.

Objectives: Lipid emulsions are commonly used for nutrition in critically ill patients. In these patients interventions resulting in deteriorated blood rheology and thereby an impaired microcirculation may be deleterious. This study examined the acute hemorrheological effects of the lipid emulsion Intralipid. We have recently shown that hyperinsulinemia exerts a negative effect on erythrocyte deformability, and here the effect of hyperinsulinemia combined with Intralipid was studied., Subjects and Interventions: Eleven healthy subjects received Intralipid (200 mg/ml) intravenously as a bolus injection (0.5 ml/kg) over 10 min and thereafter as a continuous intravenous infusion (90 ml/h) for 4 h combined with heparin (200 U/h) to stimulate lipolysis. During the final 2 h an euglycemic hyperinsulinemic clamp was added. Five subjects underwent the same protocol with the exception that saline was given instead of Intralipid and heparin., Measurements and Results: Whole blood viscosity, plasma viscosity, erythrocyte aggregation tendency and fluidity were measured by rotational viscometry. Compared with basal and control values the Intralipid infusion caused greater erythrocyte fluidity (p < 0.05) and less aggregation tendency (p < 0.05). Whole blood and plasma viscosity remained unchanged. Hyperinsulinemia had no significant effect on the hemorrheological variables measured., Conclusions: Intralipid has no deleterious effects on blood rheology in healthy subjects. Instead, it leads to improved erythrocyte aggregation tendency and fluidity. If the emulsion exerts the same effects in patients with impaired circulation, the use of Intralipid may be beneficial in these patients.

Garlic as a herbal remedy reduces a multitude of risk factors which play a decisive role in the genesis and progression of arteriosclerosis: decrease in total and LDL-cholesterol, increase in HDL-cholesterol, reduction of serum triglyceride and fibrinogen concentration, lowering of arterial blood pressure and promotion of organ perfusion, and, finally, enhancement in fibrinolysis, inhibition of platelet aggregation, and diminution of plasma viscosity. In a prospective, 4-year clinical trial with primary endpoint 'arteriosclerotic plaque volume' it was proven not only a 9 to 18% reduction and 3% regression in plaque volume of the total collective under the influence of standardized garlic powder dragees (900 mg/die LI 111), but also of some facets of the phytopharmacologic pleiotropy of this herb: decrease in LDL level by 4%, increase in HDL concentration by 8%, and lowering in blood pressure by 7%. The reduction of arterial blood pressure is due to an additional opening of K(Ca) ion channels in the membrane of vascular smooth muscle cells that effects its hyperpolarization. This membrane hyperpolarization closes about 20% of the L-type Ca2+ channels, consequence of which is vasodilatation. In human coronary arteries, the increase in vascular diameter by 4% is closely associated with an improvement of coronary perfusion by 18%. These pleiotropic effects of garlic result in a reduction of relative cardiovascular risk for infarction and stroke by more than 50%.

Purpose: To compare whole blood viscosity and erythrocyte aggregation in humans, pigs, and sheep, before and after adding water-soluble iodinated contrast medium (CM)., Methods: Two CMs were studied: iopromide (nonionic) and ioxaglate (ionic). The blood-CM viscosity was measured with a Couette viscometer. Erythrocyte aggregation was measured with an erythroaggregometer., Results: The blood-CM viscosity was increased up to +20% (relative to pure blood) with a CM concentration of 0%-10%. At CM concentrations from 10% to 50%, the viscosity decreased. The disaggregation shear stress was increased (relative to pure blood) at low CM concentration (0%-10%). When the CM concentration increased from 10% to 20%, the disaggregation shear stress was decreased, except with the pig blood-ioxaglate mixture., Conclusion: At low CM concentration the blood viscosity was increased in pig, sheep, and humans and the disaggregation shear stress was increased in pig and humans. The aggregation of sheep blood was too low to be detected by the erythroaggregometer. This rise can be explained by the formation of poorly deformable echinocytes. At higher CM concentration, the viscosity and the disaggregation shear stress decreased in relation to the blood dilution. We conclude that pig blood and sheep blood can both be used to study the effect of CM injection on blood viscosity. Nevertheless, the rheologic behavior of pig blood in terms of erythrocyte aggregation is closer to that of human blood than is sheep blood when mixed with CM. Pigs could thus be more suitable than sheep for in vivo studies of CM miscibility with blood during selective cannulation procedures.

Blood rheology alterations have often been reported in diabetic patients and may be associated with an increased risk for diabetic vascular disease. In this light a hemorheologic approach with pentoxifylline has been suggested in diabetic patients with hemorheological changes in order to improve the hemorheology approach and to evaluate the long-term effects of this treatment on the other clinical and metabolic variables. The study concerned a 10-year retrospective analysis of diabetic patients with hemorheologic alterations and angiopathic complications. Pentoxifylline (Trental 400) significantly reduced blood and plasma viscosity (at high and low shear-rates), fibrinogen and erythrocyte aggregation, and increased erythrocyte filterability throughout the study. The improvement of the hemorheologic pattern was obtained independently of the variation in glycometabolic control and body weight changes, whereas concomitant reductions of arterial blood pressure levels and of urinary excretion of albumin and total proteins was observed during the treatment. Pentoxifylline might therefore be successfully employed for long-term periods in the treatment of hemorheologic disorders in diabetic patients without effects on the metabolic pattern.

The study was conducted on human volunteers as controls as well as after administration of vanadyl sulphate on induction to high altitude (HA) at 3500 m. The plasma vanadium contents were significantly reduced in the control group on abrupt induction to HA on days 3 and 10, indicating redistribution to other organs/tissues under the stressful situation. In the vanadium salt-treated group, plasma vanadium contents were similar to those obtained at sea-level. Administration of vanadyl sulphate did not act as a diuretic. Moreover the vanadium supplemented group drank more water and also excrete less urine than the control group.

A number of epidemiologic studies have provided evidence for an increased blood viscosity in hypertensive patients. Increased viscosity could result either from hemoconcentration, thus constituting a secondary phenomenon, or, alternatively, result directly from increased intracellular calcium concentrations in erythrocytes. The latter would augment the aggregating potential of these cellular blood compounds. This currently hypothetic view remains to be elucidated. Enhanced viscosity, however, may result in increased peripheral resistance and lead to hypertensive complications. The evaluation of antihypertensive therapy should therefore take possible effects upon blood viscosity into account.

Four polycythemic young adults with inoperable cyanotic congenital heart disease were treated for 12 weeks with 20 mg/kg/day of pentoxifylline in an attempt to increase pulmonary blood flow by improving red blood cell demorability and decreasing whole blood viscosity. Treatment caused a rise in mean arterial oxygen saturation from 75-82%, a fall in the mean oxygen extraction coefficient from 47-40%, and a fall in mean oxygen consumption from 186-169 ml/min/m2. Pentoxifylline decreased whole blood, but not plasma, viscosity at all hematocrits over a range of shear rates. Two patients had significant bleeding episodes during treatment.

Coronary heart disease, stroke and peripheral arterial disease are the major causes for death and disability in industrialized countries. These diseases have a common cause: Their development is based on atherosclerotic changes of blood vessels, induced by risk factors such as elevated values of lipoproteins and fibrinogen. There is no doubt that the risk factors mentioned above are even related to a dramatically deterioration of the hemorheologic pattern, thus reducing perfusion. Due to this massage there are attempts to treat ischemia via hemorheological intervention. Although a number of different methods is available--hemodilution, defibrinogenation or oral medication--it was not possible to improve the hemorheologic pattern fast, safe, and efficient to date. A new treatment modality, utilizing the heparin-induced extracorporeal LDL precipitation (HELP), now offers the possibility to obtain therapeutical success not only in cases of severe hypercholesterolemia but even in the field of hemorheology: Using HELP a safe and rapid reduction of lipid fractions and fibrinogen has become feasible, thus providing an acute improvement of red cell aggregation and filterability of blood cells, whole blood and plasma viscosity and thereby of microcirculation. As it is known that cerebrovascular diseases are related to disturbances of the hemorheological situation, the HELP system is used at the Department of Neurology, Karl-Franzens University of Graz, for the treatment of acute stroke, cerebral multi-infarct disease but even in cases of peripheral arterial disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Ginkgo biloba special extract exerts positive effects on hemorheology and platelet aggregation, is a free radical scavenger and possesses PAD antagonistic properties, protects against hypoxia and ischemia, hampers an experimentally induced cerebral edema, has favourable properties on neurotransmitters and enhances cerebral bloodflow. Clinically EGb has proven favourable effects on intellectual deficiency, equilibrium disturbances and peripheral artery occlusions thus being a drug with a clear cut indication for these diseases.

Hemodilution is often recommended for peripheral arterial occlusive disease, yet the ultimate proof of efficacy is lacking in two randomized, placebo-controlled, double-blind, crossover trials (one using Dextran 40 and the other 10% hydroxyethyl starch 200) it has been shown to clinically benefit claudicants. During the hemodilution phases of these trials, where a 500 ml volume was exchanged against 500 ml blood, there was a significant prolongation of the walking distances. With sham-hemodilution there were no beneficial effects. These studies suggest furthermore that responders and non-responders to hemodilution can be identified prior to therapy by angiogram. A theory is developed which implies that low shear forces in vivo are a precondition for the clinical effectiveness of hemodilution. The experimental evidence supporting this theory is reported. Dextran and hydroxyethyl starch do not seem to differ with respect to their clinical response. It is concluded that hemodilution is effective for peripheral arterial occlusive disease stage II and probably even more effective in more advanced stages.

20 patients (age: 68 +/- 9 years) with an acute central artery obstruction of the retina were examined in a prospective study. All patients received a hyper- or isovolemic hemodilution depending on the haematocrit value for a period of 10 days. Clinical, hemodynamical and rheological data of these patients were recorded before therapy, after 10 days and after 6 weeks. Under this therapy, 10 patients presented an improved central vision by 2 or more stages. The degree of the distributed circulation can be determined by means of the arteriovenous passage time (AVP) and the dye bolus velocity (MDV). Compared to a control group, a significantly increased arterious-venous passage time and decreased dye bolus velocity can be observed initially. The values after 10 days of therapy and after 6 weeks were significantly improved (p less than 0.01) compared to the initial values.

The Amsterdam Stroke Study was a prospective, single-center, randomized clinical trial, investigating the effect of normovolemic hemodilution and rehydration with albumin 20% and crystalloids. All patients (n = 300) received general intensive care treatment and monitoring with a pulmonary artery catheter. The therapy was individually "customized" and guided on the pulmonary capillary wedge pressure of 12 +/- 3 mm Hg and for the hemodilution group on a hematocrit of 0.32 +/- 0.02 l/l. The significant differences in the subgroups emphasize the importance of a differentiation between a viscosity effect and an effect in hemodilution therapy, sometimes intensifying, sometimes counteracting each other.

In 40 patients microcirculation of skin as well as viscoelasticity of blood and plasma were investigated. 20 of them suffered from essential hypertension (group A) and were treated with metoprolol with a dosage of 50 to 200 mg per day. The rest of 20 subjects were controls (group B). In the group treated with metoprolol the values for blood viscosity were decreased in a significant manner, while skin microcirculation, blood elasticity and plasma viscosity did not show a significant difference. The results demonstrate that metoprolol is not only possible as medication in ischemic disease, but this substance can have a benefit in this indication because of its hemorheological effect.

45 consecutive patients suffering from peripheral arterial occlusive disease (PAOD) stage IIa and b were integrated in a study about the effect of hemorheological parameters due to different application times. The patients were divided into 3 subgroups with different application times: group A received the infusion during 2, group B during 4, and group C during 6 hours. The used substance was 500 ml 6% HES 200,000/0.6-0.66. Except elasticity of group A all hemorheological parameters from group A to group C show a decrease after 6 hours, the trend to the same phenomenon could be observed after 24 hours in group B and C, while group A except plasma viscosity showed even a trend to increasing values compared to onset. As a conclusion of these results, long-time application should be preferred.

This study was designed to investigate whether the positive effect occurring after infusion of a 10% hydroxyethyl starch solution 200.000/0.62 on cutaneous capillary blood flow could still be increased by using a 6% solution having a lower initial viscosity (HES 6% 200.000/0.62). A single blind study of 10 female volunteers was carried out to study the influence of a hypervolemic hemodilution using 500 ml of a 10% solution hydroxyethyl starch solution at first and that of 6% hydroxyethyl starch solution on macro- and microcirculation, transcutaneous oxygen partial pressure and blood fluidity. After hydroxyethyl starch infusion blood flow in the macro- and microvessels increased significantly. This increase occurred considerably earlier after administration of 6% solution than after infusion of 10% solution. Thus blood flow had already increased after 1 hour and continued to show a tendency of increase over about three hours. 6 hours after end of infusion blood flow had almost dropped to its initial value. The volume effect of the 6% solution immediately after infusion was less pronounced than that after infusion of the 10% solution, but it reached the value of the 10% solution at a later point in time. The course of the haematocrit reflected this process. Average decrease in haematocrit value compared to that following the 10% solution was not as pronounced at hour 3. After 6 hours the decreases were comparable. Similar observations were made of plasma viscosity and platelet aggregation. One hour after infusion plasma viscosity and erythrocyte aggregation had hardly changed but haematocrit had clearly dropped. Thus, blood viscosity at this point in time was essentially lowered.(ABSTRACT TRUNCATED AT 250 WORDS)

The concept of hemodilution bases on the presumed relation between impaired blood flow properties and the development and time course of ischaemic brain lesions. Animal experiments support this concept. However, recent clinical studies are disappointing. In animal experiments, treatment is initiated very early, almost undelayed (within 60 minutes), the experimental conditions are optimal and the animals are healthy. In contrast, there is a substantial delay between the onset of symptoms and the start of treatment in clinical routine conditions; furthermore, the cardiac reserve of elderly patients is limited. Therefore, the crucial question is: how can we create optimal treatment conditions to maximize the efficacy of hemodilution.

Omega-3 fatty acids are highly unsaturated fatty acids with a first (counted from the methyl end) double bound at the third carbon atom. Their biological effects--mainly changes of blood lipids and of the eicosanoid pattern--are due to a competitive inhibition of omega-6 fatty acids within the prostaglandin metabolism. Hemorheological effects have also been described repeatedly. A placebo-controlled, double blind study shows that red cell deformability is raised and blood viscosity decreased by omega-3 fatty acids in stepwise increasing doses. When the dose is further increased there is a drop of plasma viscosity and red cell aggregation. An open study with hyperlipoproteinemic patients confirms these effects: After 21 days of 8 capsules Ameu per day there is a significant reduction of plasma viscosity. After 56 days treatment (same dosage) blood viscosity drops and red cell deformability increases significantly. At present the evidence is growing to suggest that omega-3 fatty acids can delay atherogenesis. The above data allow the hypothesis that hemorheology may be involved in this.

The influence of hyper- and isovolaemic hemodilution using HES 200/0.5 6% (HES steril, Fresenius AG) on pain-free walking distance in patients with peripheral arterial occlusive disease stage II according to Fontaine was tested in a randomised investigation involving three groups. The increase in pain-free walking distance was significant both in the hypervolaemic and isovolaemic hemodilution group. The increase in both dilution groups did not differ but compared to a control group (infusion of Ringer lactate) it was significantly higher. Considerable changes concerning rheological parameters (decrease in haematocrit and plasma viscosity) were observed after isovolaemic hemodilution.

An open study was carried out in order to examine therapeutic effectivity of repeated administration of 6% hydroxyethyl starch 200.000/0.60-0.66 (HES). 10 patients aged 63 to 77 years with peripheral arterial occlusive disease Stage II b were given 500 ml Elohaest as a hypervolemic hemodilution for 12 days. Fasting levels of hydroxyethyl starch (HES) in serum, hematocrit, and serum-alpha-amylase were measured. During the first 4 treatment days, HES levels and serum-alpha-amylase increased in a significant manner; then it fluctuated towards a plateau without significant differences. The hematocrit decreased significantly from the beginning to the end of therapy. So it was possible to show, that during repeated application with the chosen dosage of 6% HAES 200.000/0.6-0.66 there is no dangerous cumulation of HAES.

To assess whether the viscoelastic properties of whole blood might be influenced by age, we measured viscoelasticity of whole blood (VEWB) and plasma at different shear rates in 84 healthy adult subjects. Additionally, we examined the relations between VEWB and gender, cigarette smoking, and oral contraceptive use. VEWB (shear rates 10/s and 50/s, adjusted to a haematocrit of 45%), viscosity of plasma (shear rate 10/s), aggregation index, shear resistance and flexibility index of erythrocytes were measured with an oscillating capillary rheometer and densitymeter. By means of univariate analysis, age was found to increase whole blood elasticity at low shear rates and shear resistance of erythrocytes. Concerning high shear rates, this relationship could only be established in males. The rheologic values of women who had taken oral contraceptives for at least one year were not related to age. Multiple regression analysis demonstrated that whole blood elasticity at low shear rates and shear resistance of erythrocytes were significantly related to age and the intake of oral contraceptives. On the contrary, there was no relationship between age and whole blood and plasma viscosity as well as aggregation and flexibility indices.

There is no doubt that hemorheological hemodilution in patients with ischaemic diseases improves the tissue oxygen supply, provided certain preconditions for therapy modalities are granted. As can be concluded from the title of this summary it is basically possible, not only to improve the blood flow properties but also - what is even more important - to optimize the oxygen supply of ischaemic tissue through hemodilution therapy. In the case of chronical arterial occlusive disease of the legs it was for the first time possible to establish a haematocrit value of about 40% as a guideline for the decrease of haematocrit in the course of hemodilution. This value, however, cannot be applied to other hemodilution schemes, other plasma substitutes, other states of chronical arterial occlusive disease or even other organs without specific examination. Before further comprehensive studies are initiated for instance of hemorheological hemodilution therapy in patients with cerebral ischaemia, optimal conditions should be experimentally determined in order to improve the prospects of the studies - as was proved in the case of intermittent claudication. Drawing from 25 years of clinical and scientific experience with hemodilution I would like to emphasize that today its therapeutic mechanism has been investigated to a high degree and its effectiveness in patients with peripheral ischaemic diseases as well as retinal ischaemic diseases can be considered as largely guaranteed. Contradictory results of clinical studies of cerebral ischaemia demand new clinical studies which not only should be improved as regards their design but also should contain concrete guidelines on the modalities of hemodilution therapy including the "optimal" haematocrit values which are to be reached.

The influence of 2 dextranes with the identical molecular weight of 70,000 Dalton for erythrocytes' elongation was investigated in-vitro in 12 healthy male subjects. An increasing dosage between 0.5 and 10 mg/ml Dextran (trade name: Dextran 70 "Ebewe") and Dextran B (weight-equivalent) was added and the elongation index of erythrocytes at shear-rate 50/sec was determined under fluid conditions. Dextran B showed a stronger reduction of elongation index than Dextran A with an elevation of difference up to the highest dosage. The results show that although the molecular weight is identical, differences in hemorheological properties could observed. This should be taken into consideration for volume substitution therapy.

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.

The effect of pentoxifylline on the deformability of red cells in sickle cell thalassaemia was investigated. The fluidity of the blood in sickle cell thalassaemia is disturbed and is accompanied by violent pains and irreversible tissue damage caused by capillary occlusions. After treating a 15-years-old female patient with pentoxifylline (2 g orally each day), the fluidity of the blood improved distinctly, and this correlated with a condition free of clinical symptoms. Erythrocyte filtration by Nuclepore filter increased significantly over the 6-month examination period (initial value: V rel = 0.068 +/- 0.008; after 6 months medication: 0.246 +/- 0.030). In addition, in the single-pore erythrocyte rigidometer (SER) a significantly improved passage time of individual erythrocytes could be demonstrated (initial value: 62.43 +/- 15.72 ms; after 4 weeks medication: 28.13 +/- 7.0 ms). The hitherto high number of rheological occlusions in the SER (48 +/- 30.9 from 200 individual passages) almost completely disappeared after treatment (1.7 +/- 1.2).

The effect of Streptokinase-infusion upon the flow properties of blood was investigated by viscometric and aggregometric methods. Under fibrinolytic therapy, we found in all cases a significant fall in fibrinogen content, as well as a strong reduction in plasma viscosity, velocity of red cell aggregate formation and shear resistance of red cell aggregates. In addition, a drop in apparent blood viscosity at all shear rates was found. In no case, a total desaggregation of red cell was noted. The hematocrit value remained practically constant; consequently, the drop in apparent blood viscosity at high (160 s-1) shear rates and intermediate (8 s-1) shear rates can be solely accounted for by the observed drop in plasma viscosity. At low shear rates (2.3 s-1) the observed drop in apparent viscosity is partly caused by aggregation desaggregation, but mainly by a drop in plasma viscosity. The presented results again confirm that the method of rotational viscometry only incompletely records the improvement in the flow properties of blood that are caused by a therapy aimed at a reduction of the plasma fibrinogen content.

There are quite a great variety of drugs available for treating the disorders of venous blood flow and its consequences. At this point it may be cautioned against applying out of each group a representative in form of a combination of drugs. Undesired changing effects must be taken into account even though adequate results are not yet submitted for all substances. The potency of anticoagulants is known by the numerous antiinflammatories which mainly is based on the changes of protein binding. Drug therapy of the disorders of the venous blood circulation alone does not suffice, since it cannot cancel the morphological changes. It is a part of a more comprehensive therapy and should support the physical and surgical procedures.

While investigating the initial effects of low carbon monoxide concentrations on haemorheology and the arterial wall, minipigs were exposed to CO-air mixtures with 160, 185, and 420ppm CO. The daily exposure time was 4h. Exposure to 160 and 185 ppm CO led to a significant increase of platelet aggregation. Four hundred twenty parts per million CO caused an increase in haematocrit, blood and plasma viscosity, and in platelet aggregation. When examined by light microscopy, there were no changes in the arterial wall, whereas scanning electron-microscopic examinations revealed adhesions of shape-changed platelets on the arterial endothelium in some cases already after a single 4-h exposure to 160 or 185 ppm CO. After 4 x 4-h exposures to 420ppm CO there were mixed microthrombi on the arterial endothelium. According to preliminary transmission electron-microscopic studies these adhesions of platelets and also adhesions of mononuclear elements can always be related to foci of degeneration in the endothelial cells. These examinations showed that low concentrations of carbon monoxide can cause both haemorheological and morphological changes in the arterial wall. The further development of these changes under chronic CO exposure and a possible significance of the environmental hygiene beyond cigarette smoking has to be clarified by long-term experiments.

Erythrocytes were suspended in dextran solutions of phosphate buffered saline with solution osmolarities from 400 to 20 mosM/kg. The dilute suspensions were subjected to linear shear and their deformation determined by laser diffractometry (Ektacytometer). Cell volumes were measured using a Coulter counter following fixation in glutaraldehyde to eliminate the influence of deformability on the volume measurement. Minimum deformability generally agreed with the maximum cellular volume produced by hypotonic solutions. However, reduced deformability was observed for both hyperosmotic and hypoosmotic conditions. The oncotic effect of the dextran delayed hemolysis to surprisingly low values of solution osmolarity. In contrast with the usual osmotic fragility results, in the hypotonic dextran solutions there was no evidence of hemoglobin release. At low shear stresses, deformability was found to be enhanced by reducing intracellular viscosity (via osmotic water transport into the cell). However, the maximum cellular deformation obtained at high shear stress was always less than that for the normal discocyte at normal osmolarities.

They are different methods of medical treatment in Menière's disease. 1. The dehydration of the hydrops by diet, diuretics, hypertonic solutions and glycerol. 2. Improvement of the blood supply by carbon dioxide, by myotropic and neurotropic vasodilators or by decreasing the blood viscosity and by medical or surgical paralysis of the sympathetic nerve. The optimistic results seen by acupuncture or neural therapy are not confirmed. - Experimental and double blind studies with betahistin (vasomotal) showed a significant effect in improving the blood circulation of the inner ear and the symptoms of Menière's disease. 3. Sedatives especially neuroleptics and tranquilizers were successful only by suppressing the symptoms, but are not a causal treatment. The same mechanism is supposed for procain and lidocain. 4. Partial destruction of the inner ear has been produced by local application of anesthetics or ototoxic antibiotics. These methods succeed in relieving vertigo and save the hearing in most cases.

The novel alkylxanthine, denbufylline [1,3-di-n-butyl-7-(2-oxopropyl)-xanthine] has been examined, in vitro, for effects on the viscosity of rat whole blood and on the filterability of rat blood cell suspensions. For comparison, pentoxifylline was also examined for rheological activity. Denbufylline reduced the viscosity of whole blood at all shear rates utilised, up to 128.5 s-1. The effect was, however, more pronounced at a low (0.7 s-1) than at a high (94.5 s-1) shear rate indicating that the compound reduces blood cell aggregation and increases blood cell deformability. Denbufylline also increased the filterability of blood cell suspensions. This is further evidence that the compound increases the deformability of blood cells. Denbufylline elevated the filterability of both pure erythrocyte and mixed erythrocyte/leucocyte suspensions, the effect being greatest with the latter. This suggests that denbufylline may influence the deformability of both red and white blood cells. However, the effect on white blood cells, under the experimental conditions employed, is apparently more marked. Pentoxifylline also reduced the viscosity of rat whole blood and increased the filterability of rat blood cell suspensions. However, denbufylline was 10-100-fold more potent in these tests than pentoxifylline.

One of the possibilities to ameliorate blood perfusion is the modification of the rheological properties of blood. Hemodilution, enzymatic defibrinogenation and oral drugs are available at present to achieve this aim. Hemodilution is clinically successful with certain indications. The efficacy of enzymatic defibrinogenation cannot be judged finally. Within the group of rheologically active drugs a variety of substances are of proven effectiveness. Yet it is open whether this is brought about exclusively by hemorheological mechanisms.

In a multicenter, randomized trial of streptokinase in acute myocardial infarction one group of patients was given streptokinase for 24 h; the remainder served as controls and received a placebo infusion instead. Coagulation assays and rheological measurements were serially performed on patients entered into the trial at one of the participating centers. Streptokinase was found to improve considerably the flow properties of blood for a period of time exceeding the duration of its administration. These results may well explain the positive clinical effect of streptokinase therapy observed in this trial.

First prophylactic and therapeutic possibilities in cor pulmonale are shown on the basis of its pathogenesis. Our own results illustrate the effect of therapy of the underlying lung disease and of the concomitant respiratory insufficiency on the pulmonary arterial hypertension. The relationship between pulmonary artery pressure (PAp), arterial oxygen tension, forced expiratory volume of 1 second (FEV1%VC) and slow inspired viral capacity (VC) is analysed. In obstructive respiratory disorders the PAp rises when FEV1 falls below 40% of VC, in restrictive disorders when VC falls below 70% of predicted rate. 27 patients with chronic obstructive lung disease were treated with bronchodilator aerosols by intermittent positive pressure breathing (IPPB) during 2 years after a control period of 2 years: VC and FEV1 improved, the increase of total lung capacity and the deterioration of arterial blood gases came to a halt. The elevated PAp was always significantly reduced by oxygen therapy or IPPB or the combination of both. Finally, the rationale for avoiding physical stress in established cor pulmonale is illustrated: in healthy men PAp increases by less than 20% when cardiac output is doubled. In patients with cor pulmonale PAp rises to three times the initial value under the same conditions.

In patients with primary hyperlipoproteinemia (23 patients type II a and II b, 13 patients type IV), changes in lipoprotein concentrations (lipid fraction), fibrinogen concentrations, in kinematic serum and plasma viscosity (determined by means of a capillary viscosimeter) and changes in relative apparent viscosity at shear rate 46 s-1 and 115 s-1 (determined by means of a plate-cone-viscosimeter) were measured before and after a clofibrate therapy (2 X 1 g/day) lasting for 7 to 9 weeks. Serum and plasma viscosity was lowered significantly in both types II and IV. The apparent viscosity decreased at shear rate 46 s-1 in type IV, whereas it remained unchanged in type II. Moreover, there exists a qualitative correlation between changes in serum viscosity and changes in lipoprotein concentration. Fibrinogen concentration remained unaltered.

Twelve patients (age 33-77 years, mean age 68.4 years) with peripheral vascular disease (PVD) stage III-IV received continuous intravenous infusions of 5 ng prostacyclin (PGI2)/kg/min and physiological saline for 7 days. The administration was randomized and double-blind with an interval of 7 days between the infusions. During PGI2 infusion systolic blood pressure fell significantly from 147.8 +/- 4.8 mm Hg to 140.6 +/- 4.0 mm Hg (P less than 0.01) and returned to 144.5 +/- 4.9 mm Hg post infusion. Transcutaneous pO2 (tcpO2) measured on the instep of the affected limb increased significantly by 8.9 +/- 3.8 Torr during PGI2 infusion and remained elevated during the subsequent week. A significant reduction of pain was observed from the 5th day of PGI2 infusion, lasting for at least the following observation period. Platelet cAMP increased from 18.8 +/- 1.5 pmol/10(8) platelets to 24.7 +/- 1.6 pmol/10(8) platelets on the 3rd day of PGI2 infusion (P less than 0.01). Spontaneous platelet aggregation was also significantly reduced during PGI2 infusion. However, 7 days after the infusion thromboxane B2 (TXB2) in plasma and spontaneous platelet aggregation significantly increased in comparison with the preinfusion values, indicating a rebound phenomenon. The clinical outcome was favorable in 9 of 12 patients, was unchanged in two patients, while progressing to limb amputation in one patient.

In a series 40 subjects without manifest vascular disorders received 1000 mg Calcium dobesilate (Doxium). Before and 3 hours after application the viscoelasticity of whole blood as well as plasma viscosity and the hematocrit were determined. The statistical analysis was performed by Wilcoxon-test. The viscosity of whole blood and the hematocrit decreased with a significance of p less than or equal to 0.001, whereas the elasticity decreased in a significance manner of p less than or equal to 0.01. Plasma viscosity remained uncharged. The results show an effect of hemodilution, which could be very important for treatment of hyperviscosity.

Ten diabetic children supplemented their normal diets with 0.45 g/kg/day guar gum for 4 weeks. They experienced a decrease in (1) plasma fibrinogen, (2) insulin requirement, (3) serum osmolality and (4) plasma viscosity; and an increase in serum albumin and total serum protein concentrations. The decrease in plasma viscosity, which was statistically significant, depended on the increase of albumin and the decrease of fibrinogen and may have some significance to the development of diabetic microangiopathy. The sequence of events eventually leading to a decrease of plasma viscosity is possibly mediated by gip and glucagon, consecutively.

Using a hyperosmolar erythrocyte model, the authors studied the effect of changes in red cell deformability on whole blood viscosity and investigated the possibility of using pentoxifylline to modify red cell deformability and whole blood viscosity. In vitro studies reveal a significant correlation between the two parameters in as much as they are inversely proportionate, i.e. viscosity increases as red cell deformability decreases and vice versa. Addition of pentoxyfylline improves impaired red cell deformability under hyperosmolar conditions and simultaneously produces a reduction in whole blood viscosity.

The clinical effect of bag-plasmapheresis was investigated in 60 patients with peripheral arterial occlusive disease stage II according to Fontaine. The initial number of patients was subdivided in three groups of 20 individuals using a randomised double-blind placebo-controlled design. Each patient gave 300 ml of blood twice a week for a 6 week duration. Blood plasma was separated in two groups and replaced with Hydroxyethyl-starch (200/0.5 10%) in group 1 and with Laevulose 5% in group 2. Patients in group 3 received their whole blood without any processing. All patients had to undergo a physical training of 45 minutes three times a week. The group who received Hydroxyethylstarch presented a 20% increase in walking distance whereas the increase in the Laevulose group was 5% and approximately 1% in the group receiving whole blood. The increase in walking distance in the Hydroxyethylstarch-group was significant on the 0.1%-level and significantly better than the improvement in walking distance of the other groups. Additionally in this group plasma viscosity showed a 3% decrease, erythrocyte aggregation was reduced by 10%. Results in the Laevulose group were only half as good as in the Hydroxyethylstarch group while parameters remained unchanged in the whole-blood-group. Bag plasmapheresis with Hydroxyethylstarch as substitute leads to an improvement in the walking capacity and blood fluidity thus offering a promising therapy for peripheral vascular occlusive disease.

The possible effect of pentoxifylline (Trental) in sickle celle disease was tested in 2 clinical trials: a controlled double-blinded intravenous study involving patients hospitalized with painful crises and an ublinded 5-month oral study in steady state patients. In the intravenous trial 29 painful episodes were treated in 16 patients. Complete blood counts, serum chemistries, red cell density gradients, intracellular pH, p50, whole blood viscosity, plasma viscosity and red cell distribution widths were monitored daily during the hospital admission. We confirmed the decrease of dense red cells during crisis and found, in addition, the related significant decrease in whole blood p50. There were no major differences in any of these parameters when pentoxifylline was compared to placebo for each individual day. When the data was examined over time, minor differences emerged. The red cell distribution width, the number of cells in density fraction SS2 (discocytes) and the plasma viscosity were all slightly higher over time in the pentoxifylline group than in the control group. In the oral group 23 patients were monitored for the same parameters on seven visits during a five month period. Administration of oral pentoxifylline produced no changes from baseline for all parameters examined except for a statistically significant, but minor, increase in plasma viscosity demonstrable for these patients during one visit only. We conclude that pentoxifylline has little effect on laboratory parameters in sickle cell disease.

Rheological therapy, as an immediate treatment in conjunction with physical therapy and the removal of risk factors, plays a significant role in the management of patients with peripheral vascular disease experiencing reduced walking tolerance. An essential element of rheological therapy is hemodilution. Currently, is still uncertain which plasma substitute solution would be the most appropriate in such cases. This study compared the effectiveness of low molecular hydroxyethyl starch to low molecular dextran during a 16-day hemodilution in combination to physical therapy. The clinical improvement observed with both plasma substitute solutions was comparable, yet in view of the cardiac volume overload, dextran demonstrates greater circulatory stress due to the transient pressure increase and more side effects. For this reason, we prefer to administer low or middle molecular hydroxyethyl starch in the dilution treatment of peripheral arterial occlusive disease as a chronic degenerative vascular disease.

The basic therapy in stage IIb of peripheral arterial occlusive disease (PAOD) according to Fontaine is exercise. The aim of this study was to test whether (given initial physiological hematocrit values of 43 to 46%) a mild hypervolemic to isovolemic to hematocrit values of 40% with HES 200/0.5 10% or Ringer lactate in combination with exercise is even more favorable. In order to answer this question, 3 groups of 25 patients each were formed. One group exercised three times weekly and the second group, in addition to exercise, underwent a mild, hypervolemic to isovolemic 6-week dilution therapy with HES. In the final group the hematocrit value was reduced to the same extent by means of venesection and volume substitution with Ringer lactate. The walking distance increased in the HES group from 216 to 311 m (44%), in the Ringer lactate group from 214 to 258 m (20%), and in the exercise group from 213 to 242 m (14%). In comparison of the groups, the increase in pain-free walking distances in the HES group is found to differ significantly from those in the other groups. It was clearly demonstrated that hemodilution with HES in combination with exercise brings about a clinical effect of an order three times of that achieved by exercise alone. Venesection with subsequent administration of Ringer lactate and exercise is superior to exercise alone, but is markedly inferior to the combination therapy with HES.