Evaluation of Laser-Doppler-Fluxmetry for the diagnosis of microcirculatory disorders.

BACKGROUND: The laser Doppler fluxmetry (LDF) is a non-invasive method to assess skin blood perfusion, measuring the flow of blood cells inside a tissue volume without harming the tissue. In the diagnosis of skin circulation disorders, the results of the LDF measurement are generally used in such a way that "normal" (or non-ill) or "pathological" values are achieved by comparison with a reference sample, for example of apparently healthy subjects. MATERIAL AND METHODS: In this study, the values of LDF for the diagnosis of microcirculatory disorders in patients with coronary artery disease (n = 20) or in patients with microcirculatory disorders, already diagnosed by capillary microscopy (n = 46), were examined. RESULTS: The mean values of LD amplitudes in the four frequency windows for patients with coronary artery disease were in the reference range. However, some of the patients showed reduced LD values: in eleven of the twenty patients, one or more mean LD amplitudes were below the reference range. Four of the eleven patients had pathologically decreased capillary erythrocyte velocities of very = 0.09-0.21 [mm/s], while the other seven patients had normal blood circulation at rest.For all patients with a proven cutaneous microcirculatory disorder, the mean LD amplitude in at least one of the frequency windows FF2 to FF4 was pathologically reduced. CONCLUSION: The Laser-Doppler fluxmetry method used in the study allows the reliable diagnosis of cutaneous microcirculatory disorders.

[Choosing wisely recommendations in angiology]. / Klug-entscheiden-Empfehlungen in der Angiologie.

BACKGROUND: The Choosing wisely initiative addresses measures of high medical impact which are frequently not appropriately performed according to expert opinion. OBJECTIVE: To increase the quality of indications by providing supportive information on diagnostic and therapeutic measures in the field of angiology. MATERIALS AND METHODS: As part of the Choosing wisely initiative, the German Society of Angiology has constructed five positive recommendations on underused measures and five negative recommendations concerning those possibly overused. The recommendations were validated by the twelve professional societies of the German Society of Internal Medicine in a consensus conference. RESULTS AND DISCUSSION: The recommendations cover a broad spectrum of diagnostic and therapeutic modalities, such as the role of ultrasound examinations in vascular diseases, screening for abdominal aortic aneurysms, diagnosis and therapy of peripheral artery disease (PAD), investigation of chronic ulcers, therapy of varicosis, and finally, the problems associated with using anticoagulants in PAD or thrombosis. By discussing the evidence, we aim to demonstrate that not all medically possible measures are actually appropriate in every situation.

Effect of Ioxaglate on the cutaneous microcirculation in patients with coronary artery disease: Randomized, double blind, placebo-controlled study.

Radiographic contrast media (RCM) can initiate microcirculatory disorders. This study was performed to investigate effects of Ioxaglate on the cutaneous microcirculation. The investigation was carried out as prospective randomized double-blind comparison in parallel-group design on two groups of n = 10 patients each who had to undergo a diagnostic coronary angiography.The confirmatory parameter of the study was mean erythrocyte capillary velocity [vRBC in mm/sec]. VRBC in the ipsilateral nail-fold capillaries was recorded continuously for 3 min before and 6 min after injection of RCM or isotonic saline solution in the A. axillaris respectively, and was evaluated off-line.VRBC in nailfold capillaries was found to be decreased by Ioxaglate by 34% 150 seconds after injection, while isotonic NaCl solution immediately induced a slight increase of 14%.

Tissue oxygen partial pressure in the tibialis anterior muscle in patients with claudication before, during and after a two-stage treadmill stress test.

BACKGROUND: The role of the microcirculation in the pathophysiology and symptoms of peripheral arterial obliterative disease (PAOD) has been progressively emphasized during the past decades. Under resting conditions, already, the tissue oxygen partial pressure in the m. tibialis anterior (pO2im) is reduced to about 50% compared to healthy subjects. METHODS: In the framework of this study the pO2im of patients with PAOD stage II according to Fontaine (n=16) in the m. tibialis anterior was measured under resting conditions and during walking on a treadmill in comparison to healthy subjects (n=10). RESULTS: Under resting conditions the pO2im only marginally differed between PAOD patients and healthy subjects. But during exercise the pO2im dropped significantly more severely in PAOD patients and a return to baseline values could only be reached when the treadmill was stopped and the patients stood still. The pO2im minima correlated clearly with the clinical symptom of calf pain. CONCLUSION: The data revealed that the pO2im values were lower in PAOD patients and dropped significantly faster during walking compared to the pO2im values in healthy subjects. The pO2im decrease correlated with the calf pain occurring when the pO2im values approached or fell below 10 mmHg.

[Management of peripheral vascular disease based on current guidelines. Peripheral artery occlusive disease of the iliac and femoral arteries and carotid artery stenosis]. / Management peripherer Gefäßerkrankungen gemäß aktueller Leitlinien. Periphere arterielle Verschlusskrankheit vom Becken-Bein-Typ und extrakranielle Karotisstenose.

The article summarizes the recommendations of current European and American guidelines concerning the diagnosis and treatment of peripheral arterial occlusive disease and carotid artery stenosis. In comparison to older recommendations, current guidelines concerning endovascular treatment and concomitant medical therapy have been changed in recent years. With the exception of very complex and long lesions, endovascular methods are seen as the therapy of choice for revascularization of the iliac and femoral arteries. For cardiovascular risk reduction, patients with symptomatic peripheral arterial disease and stenosis of the carotid arteries should receive antiplatelet as well as statin therapy and should not be treated different from patients with coronary artery disease.

Laser Doppler flux measurement for the assessment of cutaneous microcirculatio--critical remarks.

Back scattered Laser Doppler (LD) signals are composed of two different individual signals. The number of the moving particles and the speed of the particles in the measured tissue volume determine the frequency shift and the band width of the Doppler signal. The dependence of the Laser Doppler flux on the number of scattering particles is highly nonlinear: at very low hematocrit and high speed the axial migration of the cells to the centre of the blood vessels is very strong, so that in these cases - because of the parabolic flow profile - the Doppler flux measurement overestimates the mean real blood flow (up to two- or three-fold). The opposite is the case when the hematocrit is very high, then the blood flow might be underestimated (due to the increased amounts of blood cells near the vessel wall). In addition, a very change in number of moving particles - as can occur during the postprandial phase or during therapy - can change the signal also at a constant cell number. Also, it must be mentioned that the LD signal possibly is not only reflected by moving blood cells in the different skin layers but also by blood cells flowing in tissues below the skin (particularly below atrophied skin areas of older patients) so that in such cases the LD Flux signal reflects not exclusively the skin blood flow. Therefore, LD flux at rest may still be within the normal range even in advanced states of disease, since the scattered light is sampled from a tissue volume which may contain also non-nutritive shunt vessels. This critical analysis of the LD signals of course shall not lead to an overall rejection of the application of laser Doppler systems. Actual progress only can, however, be obtained under the exact consideration of anatomical conditions, technical restrictions and when generalizations are avoided.

Microcirculation in hypertensive patients.

Regardless of the mechanisms that initiate the increase in blood pressure, functional and structural changes in the systemic vasculature are the final result of long-standing hypertension. These changes can occur in the macro- but also in the microvasculature. The supply of the tissues with oxygen, nutrients, and metabolites occurs almost exclusively in the microcirculation (which comprises resistance arterioles, capillaries and venules), and an adequate perfusion via the microcirculatory network is essential for the integrity of tissue and organ function. This review focuses on results from clinical studies in hypertensive patients, which have been performed in close cooperation with different clinical groups over the last three decades. Intravital microscopy was used to study skin microcirculation, microcatheters for the analysis of skeletal muscle microcirculation, the slit lamp for conjunctival microcirculation and the laser scanning ophthalmoscope for the measurement of the retinal capillary network. The first changes of the normal microcirculation can be found in about 93% of patients with essential hypertension, long before organ dysfunctions become clinically manifest. The earliest disorders were found in skin capillaries and thereafter in the retina and the skeletal muscle. In general, the disorders in the different areas were clearly correlated. While capillary rarefaction occurred mainly in the retina and the conjunctiva bulbi, in skin capillaries morphological changes were rare. A significant decrease of capillary erythrocyte velocities under resting conditions together with a marked damping of the postischemic hyperemia was found, both correlating with the duration of hypertension or WHO stage or the fundus hypertonicus stage. Also the mean oxygen tension in the skeletal muscle was correlated with the state of the disease. These data show that the microcirculatory disorders in hypertension are systemic and are hallmarks of the long-term complications of hypertension. There is now a large body of evidence that microvascular changes occur very early and may be important in their pathogenesis and progression.

Influence of rheological parameters on the velocity of erythrocytes passing nailfold capillaries in humans.

One thousand two hundred and fifty-six subjects (apparently healthy subjects and patients with cardiovascular diseases) were registered in a prospective study including demographical and clinical data, rheological parameters (hematocrit, plasma viscosity, erythrocyte aggregation, erythrocyte deformability) as well as the erythrocyte velocity in human nailfold capillaries under resting and postischemic conditions. A multivariate regression analysis showed that under resting conditions there was no correlation between rheological parameters and erythrocyte velocity in capillaries. The blood flow regulation seemed to be so effective, that pathological changes of the blood fluidity showed no effect on the velocity of an erythrocyte passing the capillaries. During vessel paralysis in the early phase of the postischemic hyperemia following a stasis of three minutes in the vasculature distal to a pressure cuff at the upper arm a very clear correlation between the plasma viscosity and the maximum postischemic erythrocyte velocity in ipsilateral cutaneous capillaries could be observed (p < 0.0001) while none of the other rheological parameters seemed to play a role. In a subgroup of diabetic patients the erythrocyte aggregation (measured during stasis) also correlated with the erythrocyte velocity (p = 0.0175) besides the plasma viscosity. This shows that a correlation of rheological parameters with the capillary perfusion could only be found during vessel paralysis. In of diabetic patients besides the plasma viscosity also the erythrocyte aggregation correlated with the mean capillary erythrocyte velocity. Theses results are in agreement with the hypothesis from Barras that plasma viscosity determines the perfusion of microvessels. Under certain conditions e.g. diabetic disorder, also the erythrocyte aggregation plays a role.

Correlation between postischemic vasodilation of the arteria brachialis and of the postischemic hyperemia in the adjacent microvascular bed.

BACKGROUND: Endothelial cells secrete different mediators depending on biochemical and/or biophysical conditions, which can lead to vasodilation or vasoconstriction, respectively. Impaired endothelial responsiveness to specific vasodilator stimuli has been used as a surrogate marker of cardiovascular risk. Multiple methods allow testing endothelial responses in both microvessels and conduit arteries, but it is still unclear whether there is a relationship in endothelial function between these two different vascular beds. MATERIAL AND METHODS: In order to examine, whether such macrocirculatory data might correlate with data obtained in the supplied microvessels, a parallel investigation in the brachial artery (BA) and the supplied nailfold capillaries was performed. The duration and amplitude of the postischemic hyperemia (stasis in the vasculature of the left arm using a blood pressure cuff for 3 minutes) were measured (ultrasound technique) and simultaneously the amplitude and duration of the postischemic hyperemia in ipsilateral nailfold capillaries (intravital capillaroscopy). RESULTS: There was absolutely no correlation between the duration (n = 153, r = 0.076, p = 0.3493) of the diameter increase in the BA and in ipsilateral nailfold capillaries. CONCLUSION: The regulation of the cutaneous microcirculation did not follow diameter changes of the conduit artery (BA) but seems to be dominated by the precapillary arterioles.

[Secondary prophylaxis of venous thromboembolism]. / Sekundärprophylaxe der venösen Thromboembolie.

Making decisions about any modality of secondary prophylaxis in patients with venous thromobembolism (VTE) has to balance the risk of bleeding induced by anticoagulants against the benefit of reducing the risk of recurrent disease. It has to be kept in mind that the magnitude of risk is not only defined by the number of events per time period but also by the impact of the event on the fate of the patient. With standard intensity vitamin K antagonists (VKA), the risk of bleeding is more closely related to comorbidities than to other factors, eg age. The risk of VTE recurrence differs largely between patient groups. The criterion of presence or absence of a permanent or transient clinical trigger factor for the actual VTE episode has a greater impact than an abnormal result in thrombophilia testing. The standard period of secondary prophylaxis for proximal DVT and for PE is three to six months. The concept of prolonging this period for several months according to the risk of recurrence is seriously challanged by the observation that the prolongation period seems to delay recurrencies rather than truly avoiding them. For this reason, patients who clearly are threatened by recurrent episodes should receive indefinitive secondary prophylaxis. This is the case for cancer patients, patients with the antiphospholipid syndrome, and those who belong to families with severe and symptomatic protein C, protein S, or antithrombin deficiencies. Patients with recurrent VTE, with idiopathic VTE, or with combined thrombophilic conditions may only benefit from indefinitive secondary prophylaxis if the bleeding risk of the anticoagulant regimen under consideration is very low.

[Risk adapted therapy in vascular diseases: antihypertensive treatment in peripheral arterial disease]. / Risikoadaptierte Therapie von Gefässerkrankungen--Antihypertensive Behandlung bei AVK.

Arterial hypertension must also be consistently treated in patients with PAD. Current guidelines and recommendations have to be considered, although in some patients the walk performance may be affected temporary by blood pressure dropping. In PAD, ideal antihypertensives are ACE inhibitors, AT1 receptor antagonists, calcium channel blockers and also alpha receptor blockers in combination. Beta receptor blockers-indicated in coronary heart disease-do not influence pain-free walking distance (PFWD) in patients with PAD. Diuretics should only be given in low dosage and in combination with other antihypertensive drugs in order to avoid a decrease of blood flow ability with clinical events.

Effect of LDL apheresis on oxygen tension in skeletal muscle in patients with cardiac allograft vasculopathy and severe lipid disorder.

In this study, the extent to which intramuscular pO2 is influenced by a single HELP-apheresis (Heparin-induced Extracorporeal LDL Precipitation) was investigated in 10 patients with cardiac allograft vasculopathy (CAV) and severe lipid disorder. For this purpose, a sterile flexible pO2 microcatheter was inserted into the anterior tibial muscle and pO2 monitoring was begun 10 minutes before starting apheresis treatment. The intramuscular pO2 values were recorded continuously until the end of apheresis treatment and a subsequent 30-minute further observation phase. The patients with CAV and severe lipid disorder presented with 11.6+/-3.8 mmHg significantly and pathologically reduced intramuscular pO2 (p<0.001). LDL apheresis resulted in a significant increase in pO2 in the anterior tibial muscle. Thirty minutes after the end of HELP-apheresis, intramuscular partial oxygen pressure had increased by 162% and showed values at this point, 30.3+/-9.8 mmHg, similar to those found in healthy subjects.

Effect of naftidrofuryl on intramuscular partial oxygen pressure (pO2) prior to, during and after physical load on the treadmill in apparently healthy subjects.

Previous studies demonstrated that naftidrofuryl increased the cutaneous and intramuscular tissue pO2 at rest. The presented open prospective pilot study is to investigate in apparently healthy subjects (n=12) whether naftidrofuryl also affects pO2 in situations of muscular stress. The pO2 is measured with a flexible probe in the anterior tibial muscle during treadmill exercise prior to and after one-week treatment with 100 mg of naftidrofuryl administered three times a day. The intake of naftidrofuryl proved to significantly affect the intramuscular partial oxygen pressure. With 38.6+/-22.9 mmHg, the pO2 is at rest already significantly (p<0.05), i.e., approx. 40% higher after one week of intake than before treatment (27.3+/-12.1 mmHg). This higher pO2 level is maintained during exercise. The higher the physical load, the larger the difference in pO2. While under naftidrofuryl treatment the measured pO2 values exhibit the tendency to increase during the first exercise phase (at a load of 3 km/h and a gradient 5 degree), the differences are even significant under higher physical stress (at 5 km/h and a gradient of 10 degree). With 33.9+/-12.0 mmHg the mean minimum pO2 determined at the higher load level still ranges above the basal pO2 measured before the start of naftidrofuryl treatment.

Intramuscular oxygen partial pressure in the healthy during exercise.

The oxygen partial pressure (pO2) in the anterior tibial muscle was measured in n=12 (6 physically active and 6 sedentary) apparently healthy subjects. This was the first time a flexible micro catheter with an outer diameter of 0.45 mm was used during skeletal muscular activity in men. A two level tread mill test which is used in the diagnosis of peripheral arterial occlusive disease was chosen to induce physical stress. In the healthy volunteers a pO2 increase was noted at the beginning of exercise. This was followed by a pO2 decrease because of an increased O2 demand in the working muscle. The initial pO2 increase was thought to be due to the recruitment of capillaries and not the subsequently increased heart rate. At rest and during activity pO2 values were higher in physically active subjects than in the sedentary and the exercise induced decrease of pO2 values was slower and in addition to this the compensation to baseline values quicker.

Influence of Iodixanol-270 and Iopentol-150 on the microcirculation in man: influence of viscosity on capillary perfusion.

UNLABELLED: PURPOSE, MATERIAL AND METHODS: The aim of this study was to investigate the influence of direct intraarterial application of the contrast agents Iodixanol-270 and Iopentol-150 on the capillary perfusion. This was accomplished through continuous recording of the capillary perfusion in the nailfold capillaries of the right hand before and after a bolus injection of 20 ml of contrast agent into the right axillary artery. RESULTS: After injecting 20 ml of Iodixanol-270, which has a high viscosity compared to the plasma viscosity, a statistically significant decrease in the erythrocyte velocity of 60.8% from 0.439+/-0.273 mm/s to 0.172+/-0.090 mm/s was observed already 10 s after the injection (p = 0.0001). The decreased velocity was maintained until the end of the observation period of 6 min. In contrast to this finding, no change in the erythrocyte velocity was observed after injection of 20 ml of the low-viscous Iopentol-150 (p = 0.1508). CONCLUSIONS: The erythrocyte velocity in cutaneous capillaries therefore strongly depends on the viscosity of the contrast agent.

Influence of radiographic contrast media (Iomeprol 350 versus Iopentol 350) on cutaneous microcirculation: single-center prospective randomized double-blind phase iv study in parallel-group design.

OBJECTIVE: This single-center, prospective, randomized, double-blind phase IV study in parallel-group design was carried out to investigate whether either of two different x-ray contrast media (iomeprol 350 or iopentol 350) injected into the axillary artery has any influence on cutaneous microcirculation. METHODS AND RESULTS: The investigation was carried out on two groups of patients (n = 10 in each group) who had to undergo a diagnostic heart catheter angiography. The confirmatory response variable for the study was the mean capillary erythrocyte velocity (mm/sec). Blood flow through the ipsilateral nail-fold capillaries was recorded continuously for 3 minutes before and 6 minutes after the injection of the randomly assigned x-ray contrast medium, and was evaluated off-line. A contrast medium-induced, rheologically determined disturbance of the microcirculation was found, which was due to two different effects. First, the high intrinsic viscosity (iopentol = 12.3 mPa.sec) led to an immediate reduction in capillary blood flow. This did not occur in the case of iomeprol (intrinsic viscosity = 7.5 mPa.sec). Second, the contrast medium molecules cause a morphological change in the erythrocyte membrane; echinocytes are formed and are further desiccated depending on osmolality of the contrast medium. CONCLUSION: The time course of the conversion of erythrocytes into echinocytes leads to a maximum reduction in capillary erythrocyte velocity of 30 seconds after the bolus of contrast medium. For the more viscous contrast medium of higher osmolarity (iopentol), this led to a significant overall reduction of up to 48.6% in capillary blood flow (p < 0.0001) that lasted for up to 150 seconds, while iomeprol did not significantly affect capillary blood flow (p = 0.2759).

[Incomplete thrombosis of the inferior vena cava, a cause of chronic recurrent lung embolism. Diagnostic possibilities and case report]. / Die inkomplette V. cava-inferior-Thrombose, eine Ursache für chronisch rezidivierende Lungenembolien. Diagnostische Möglichkeiten und Fallbeschreibung.

Detection of complete inferior vena cava thrombosis is relatively simple because of the clinical symptoms and the pathological results of cw Doppler sonography in the region of the common femoral vein. Drainage volume detectable by means of venous occlusion plethysmography is considerably reduced during the acute phase, but normalizes with increasing degree of collateralization. In case of incomplete inferior vena cava thrombosis clinical signs, cw. Doppler sonography and venous occlusion plethysmography are not very relevant. Therefore, imaging technique is additionally required. Basing on a case report, the article demonstrates that ultrasound-B-method and echocardiography, or preferable endoechocardiography, may contribute to a more reliable diagnosis. Cavography is still the gold standard if invasive therapy is planned.

[Venous capacity and drainage volumes of arm veins]. / Untersuchungen zu Venenkapazität und Drainagevolumen der Armvenen.

On 29 test persons after clinical angiological and cw-Doppler-sonographic exclusion of an obstruction of the deep veins and an arterial occlusive disease on the upper extremities the capacity of the veins and the drainage volume were determined by means of the venous-occlusion plethysmography. The angiological measuring places Compactus 540 and Periquant 3800, respectively, of the firm Gutmann (group 1) and the 2-channel occlusion plethysmography of the former nationally owned measuring device factory Ballenstedt (VEB Messgerätewerk Ballenstedt) (group 2) were at our disposal. Apart from the obsolute values of the capacity of the veins and of drainage volume on account of the large interindividual dispersions the quotients were determined in the comparison of sides. In the two groups the drainage volume showed significantly larger values on the right arm than on the left one. In group 2 the measuring of the capacity of the veins and the drainage volume resulted in essentially larger values than in group 1. In contrast to the absolute values the quotients of the measuring values did not show any significant differences between the two groups so that it seems that these are better suitable of the judgment of the venous obstruction behaviour.

[Blood fluidity in essential hypertension, arterial occlusive disease and diabetic angiopathies]. / Untersuchungen zur Blutfluidität bei essentieller Hypertonie, arterieller Verschlusskrankheit und diabetischen Angiopathien.

Microcirculatory disturbances are important complications in hypertension, arterial occlusive disease (PAVK) and diabetic angiopathies. The special haemorrheological diagnostics for the judgment of the terminal vascular bed tended to the comprehension of the haemorheological risk. Due to the increase of the aggregation of erythrocytes and viscosity of the plasma in peripheral arterial occlusive disease and diabetic angiopathies this risk proved to be distinctly increased, in diabetes mellitus without vascular complications and essential arterial hypertension it proved less distinctly increased. In hypertension the application of diuretic drugs should be done more critically and more controlled, in order to avoid conditions of hyperviscosity with their sequels for the microcirculation. The internal therapy in PAVK and diabetic angiopathies must include the amelioration of the disturbed blood fluidity.