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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 v ery = 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.

AIM: Aim of this study was to firstly describe reproducible, objective perfusion parameters of contrast-enhanced ultrasound (CEUS) kinetics of parathyroid gland adenoma (PA) using perfusion analysis software (VueBox (R), Bracco, Italy). Thereby the efficiency of quantitative CEUS for characterization of PA should be evaluated comparing US to postoperative histopathological findings after PA resection. MATERIAL AND METHODS: 42 patients with symptoms/lab work suggestive of pHPT presented a parathyroid gland lesion in B-mode US, which was consequently analyzed by dynamic CEUS. CEUS was performed by one experienced examiner after i.v.-injection of max. 2.4 ml sulphurhexaflouride microbubbles saving digital DICOM cine loops (up to 25 s) and images. PA were evaluated during arterial, venous and late phase (up to 3 min.) for perfusion characterization. A retrospective, blinded VueBox (R) perfusion analysis of arterial phase of 28/42 PA was performed by a second, independent examiner placing 3 ROIs manually in the PA (center, rim of PA, surrounding thyroid gland tissue) to objectify findings. US findings were correlated to postoperative histology after PA resection. RESULTS: Out of 42 patients with PA findings in CEUS, perfusion analysis could be performed in 28/42 cases only as some CEUS cine loops had too much moving. In three cases the second examiner could not detect PA retrospectively, in 25 cases PA were characterized correctly resulting in a sensitivity rate of 89.3 %. VueBox (R) perfusion analysis confirmed that PA present a persisting hypervascularization of the rim with higher TTP (mean 7.93 s centrally, 8.36 s rim-sided), mTT (mean 56.6 s centrally, 64.5 s rim-sided) and lower PE (mean 10542.93 rm(2) centrally, 8909.21 rm(2) rim-sided) peripherally followed by a central wash-out during later phases. RT was comparable in all defined regions. CONCLUSION: VueBox (R) analysis of parathyroid gland CEUS examinations seemed to be a valuable tool for quantification of a PA's perfusion and can help to detect and localize hyperfunctional parathyroid glands prior to surgery.

Background Remote ischemic preconditioning (RIPC) has been demonstrated to induce potent cardioprotection in individuals experiencing coronary ischemia. A protocol combining limb ischemia and electronic muscle stimulation of the ischemic skeletal muscle (RIPC+), performed in advance of coronary artery occlusion, was superior in terms of infarct size reduction when compared to RIPC alone. Methods This study was performed to evaluate the benefit of RIPC + in humans compared to a standard RIPC protocol and a control group. Patients with a single vessel coronary artery disease undergoing elective PCI were eligible to participate in this study. ST-segment elevations from an intracoronary ECG during 3 brief episodes of coronary artery balloon occlusions/dilatation were used as the primary endpoint. Results ST-elevations significantly declined from the first to the third angioplasty in the control but remained at the same level in the RIPC and RIPC+groups. The RIPC group was characterized by the lowest ST-segment shift during coronary ischemia, which was comparable to coronary balloon occlusion number 3 in the control group, indicating successful preconditioning by the conventional RIPC method. In contrast, ST segment elevations were significantly higher in the RIPC + group. Troponin levels taken 24 h after the study procedure were significantly lower in the RIPC when compared to the control and the RIPC + group. Conclusion Our results again confirm the feasibility of remote ischemic preconditioning in patients undergoing coronary angioplasty. According to our results ischemia combined with electronic skeletal muscle stimulation was not superior to conventional RIPC cycles (skeletal muscle ischemia alone).

In cancer therapy, a number of drugs with different mechanisms of action are in clinical use, which act directly after administration without metabolism, while others only become active in the metabolites produced in the liver. Such drugs/metabolites – especially when administered parenterally – interact in high concentrations with the endothelium. Whether this induces adverse responses of the endothelial cells (EC) is barely studied for many medicaments. This pilot in vitro study revealed that the addition of cyclophosphamide (CPA) to the culture medium (5 or 10 mM, respectively) showed a clear influence on EC compared to non-treated EC: The number of adherent human vein endothelial cells (HUVEC) decreased by the addition of CPA in a concentration-dependent manner compared to the untreated control, whereby the vitality of adherent cells was not affected. In addition, concomitant with activation of the adherent HUVEC, increased migratory activity occurred. These results are in agreement with clinical events like thromboses in patients in compromised condition under therapy with CPA, as the detachment of EC might induce responses of circulating platelets leading to the adherence and aggregation with the risk of the formation of thrombi. Whether CPA acts directly or via toxic metabolites on EC will be examined in more detail in following studies.

Ultrasound contrast agents (USCA) allows the dynamic detection of blood flow of both the macro and microvasculature. An obvious prerequisite for USCAs is the unhindered passage of clinically relevant dose levels through the microcirculation especially of the lungue, where they have to pass capillaries with diameters of around 4 μm. While smaller microbubbles rapidly passed through the microcirculation along with the red blood cells, larger microbubbles, however, were observed to coalesce and interrupt the blood flow. Whether this might influence the tissue oxygen tension is unclear up to now.To examine this question a bolus of 2.4 ml SonoVue™ was injected into the suprarenal aorta at a flow rate of 10 ml/s (a dosage usually applied in the clinic). The pO2 in the outer medulla of the kidney was continuously measured using a flexible pO2 microcatheter. In addition, the SonoVue™ injection and its passage through the renal vasculature were documented by the CEUS technology to assess whether the microbubbles passed the kidney.The study revealed that SonoVue™ induced no changes of the mean oxygen partial pressure in the outer medulla which confirms that these microbubbles on their way through the medullar capillaries did not hinder the co-flow of blood through the renal microvessels in a big animal model with a renal morphology and function comparable to human kidneys. These results demonstrate that the CEUS diagnostic itself did not influence the system to be examined which is a most important prerequisite for any diagnostic method.

Magnetocardiography (MCG) has been proposed as a non-invasive and functional technique with high accuracy for diagnosis of myocardial ischemia. This study sought to investigate the incremental diagnostic value of combined quantitative and qualitative parameters of MCG to detect coronary artery disease (CAD).Ninety six patients with suspected CAD who underwent coronary angiography were enrolled in the analysis to test the diagnostic accuracy of 2 MCG parameters (a quantitative parameter of the percent change of ST-segment fluctuation score and a qualitative parameter of non-dipole phenomenon).The best cut-off value for the percent change of ST-segment fluctuation score was -51.0%. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 78.1, 73.9, 82.0, 79.1, and 77.4, in the percent change of ST-segment fluctuation score and 86.5, 84.8, 88.0, 86.7, and 86.3 in non-dipole phenomenon. The area under the curve of receiver-operating characteristics was 0.79 for the percent change of ST-segment fluctuation score and 0.86 for non-dipole phenomenon (p0.001). However, the incorporation of non-dipole phenomenon into a model with the percent change of ST-segment fluctuation score significantly improved C-statistics, indicating the enhancement of diagnostic performance in the detection of significant CAD (0.790 to 0.930; p0.001).Qualitative assessment of non-dipole phenomenon has a better diagnostic value than the quantitative parameter of percent change of ST-segment fluctuation score in the detection of significant CAD. Furthermore, this study found that the incorporation of non-dipole phenomenon into the percent change of ST-segment fluctuation score significantly improved the diagnostic performance of CAD detection.

BACKGROUND Magnetocardiography (MCG) is a non-invasive technique and to characterize the magnetic field, a pseudo-current conversion was used. The role of MCG in detecting left atrial (LA) dysfunction in patients with paroxysmal atrial fibrillation (PAF) is unknown. OBJECTIVE The aim of this study was to evaluate LA function using MCG in patients with PAF and healthy subjects, to identify possible indices to diagnose PAF. METHODS We enrolled a total of 70 subjects including 26 healthy volunteers (group 1) and 22 marathon runners (group 2) who did not exhibit any cardiac abnormalities, and 22 patients with PAF (group 3) which was documented by electrocardiography (ECG). Spatiotemporal activation graph (STAG) in base-apex and left-right direction was reconstructed. The maximum value of LA pseudo-current under rest and peak exercise were measured between the end of the P wave and beginning of the Q wave. RESULTS LA pseudo-current increase at peak exercise in PAF patients was significantly lower than in healthy volunteers and marathon runners (0.4±0.3 pT in group 3 vs. 0.8±0.3 pT in group 1 vs. 1.1±0.5 pT in group 2, p

BACKGROUND Exercise electrocardiography (ECG) is frequently used as a diagnostic measure in patients with suspected coronary artery disease (CAD). However, it has low sensitivity for the detection of CAD. Magnetocardiography (MCG) has been proposed as an alternative tool to accurately diagnose CAD. OBJECTIVE To date, a direct comparison of MCG to ECG has not been performed. This study sought to compare them for predicting the presence of significantly obstructive CAD. METHODS The patients with chest pain or other symptoms suggestive of CAD were enrolled in the analysis. All the patients underwent a clinical evaluation, exercise ECG, MCG test, and coronary angiography (CA). CAD was defined as stenosis ≥70% in at least one major coronary artery on quantitative analysis of CA. RESULTS We prospectively enrolled 202 consecutive patients who suggested CAD. The prevalence of CAD on CA was 39.1%. Sensitivity and accuracy for CAD diagnosis was higher for MCG compared with exercise ECG (sensitivities 68.4% and 40.5%, p

In the past years the microcirculation has gained increasing attention not only by basic scientists, but also by clinicians and translational researchers. In the clinical scenario, it has been convincingly described that the microcirculation is a key predictor of outcome and of central pathophysiological relevance. A vast body of evidence demonstrates the central role of the smallest vessels in inflammation, hyperviscosity, cell-cell-interaction, endothelial function, tissue edema, hemodynamic and blood flow regulation and its important role in the interaction with soluble factors. A central feature of different diseases and a strong regulator of different changes is hypoxia, the lack of oxygen. Also the microcirculation is on one hand a central component responding with dynamic changes to hypoxia but also the central place where hypoxia mediates its unfavorable effects. These changes and associated interactions are the topic of this special thematic issue "Hypoxia" in Clinical Hemorheology and Microcirculation and it seems logical that important and relevant findings are presented.

Objective— Drug-eluting coronary stents reduce restenosis rate and late lumen loss compared with bare-metal stents; however, drug-eluting coronary stents may delay vascular healing and increase late stent thrombosis. The peroxisome proliferator–activated receptor-delta (PPARδ) exhibits actions that could favorably influence outcomes after drug-eluting coronary stents placement. Approach and Results— Here, we report that PPARδ ligand–coated stents strongly reduce the development of neointima and luminal narrowing in a rabbit model of experimental atherosclerosis. Inhibition of inflammatory gene expression and vascular smooth muscle cell (VSMC) proliferation and migration, prevention of thrombocyte activation and aggregation, and proproliferative effects on endothelial cells were identified as key mechanisms for the prevention of restenosis. Using normal and PPARδ-depleted VSMCs, we show that the observed effects of PPARδ ligand GW0742 on VSMCs and thrombocytes are PPARδ receptor dependent. PPARδ ligand treatment induces expression of pyruvate dehydrogenase kinase isozyme 4 and downregulates the glucose transporter 1 in VSMCs, thus impairing the ability of VSMCs to provide the increased energy demands required for growth factor–stimulated proliferation and migration. Conclusions— In contrast to commonly used drugs for stent coating, PPARδ ligands not only inhibit inflammatory response and proliferation of VSMCs but also prevent thrombocyte activation and support vessel re-endothelialization. Thus, pharmacological PPARδ activation could be a promising novel strategy to improve drug-eluting coronary stents outcomes.

Objective Most of the detected thrombi in patients with atrial fibrillation (AF) can be found in the left atrial appendage (LAA). Interventional LAA closure recently proved to be noninferior to warfarin therapy. Whether these results can be fully translated into surgical LAA closure remains unclear. Corresponding data are still lacking. The present observational study evaluated the impact of surgical LAA closure in patients with AF undergoing cardiac surgery on postoperative thromboembolic events. Methods A prospective registry enrolled 398 patients with permanent AF undergoing cardiac surgery. Concomitant procedures were isolated surgical ablation (group I, n = 71), isolated LAA closure (group II, n = 44), and combined surgical ablation and LAA closure (group III, n = 196). The control group consisted of 87 patients without concomitant surgical ablation or LAA closure. One-year follow-up was completed in all patients. End points were thromboembolic events and death from any cause. Results Clinical baseline characteristics were comparable among the groups. General hospital mortality was 5.5% and likewise differed not significantly. Postoperatively, mean (SD) CHAD2S2-VASc score of 3.5 (1.3) differed not significantly among the groups, indicating comparable thromboembolic risk. Follow-up referred to all hospital survivors (n = 376). Herein, overall incidence of thromboembolic events was 9.8% (n = 37), with an associated mortality of 41.0%. Patients with LAA closure alone or in combination with surgical ablation had a significantly reduced incidence of thromboembolic events (6.6% vs 20.5%, P < 0.01) and consecutively improved survival after 1 year of follow-up (7.0% vs 17.1%, P < 0.01). Conclusions Left atrial appendage closure alone or in combination with surgical ablation was associated with a significantly reduced rate of thromboembolic events and consecutively improved survival after 1 year of follow-up.

BACKGROUND: Magnetocardiography (MCG) has been proposed as a non-invasive and functional technique with high accuracy for diagnosis of myocardial ischemia. OBJECTIVE: This study sought to develop a novel scoring system of MCG for predicting the presence of significant obstructive coronary artery disease (CAD). METHODS: In a training set of 108 subjects, predictors of ≥70% stenosis in at least one major coronary vessel were prospectively identified from MCG variables. The final model was then retrospectively validated in a separate set of 45 subjects. RESULTS: In the multivariable logistic regression, among those in the training set, elevated scores were predictive of ≥70% stenosis in all subjects (OR: 40.85; 95% CI: 6.28–265.90; p

Background Contrast-induced acute kidney injury (CI-AKI), a potentially life-threatening complication of iodinated contrast media in patients with impaired renal function, has attracted increasing attention in recent years. There is overwhelming evidence that the most important pre-disposing factor for a contrast-medium induced nephropathy is the pre-existence of a renal impairment. Methods The registry was performed as a part of a quality management project in the Dresden-Friedrichstadt heart catheter laboratory. In compliance with the Declaration of Helsinki/Somerset West, 9,026 patients were included between 2010 and 2015. 100 patients of these were participants in a chronic dialysis program. All patients were dialyzed on the day before angiography. In all patients a coronary angiography, in 28 patients a stent implantation and in 12 patients a surgical reconstruction had to be performed. Prior to the intervention and one, two and three days thereafter the serum creatinine was measured. Results Up to the third day after application of the iodinated contrast medium no significant changes of the serum creatinine (baseline value: 423.3±42.6μmol/l) occurred (ANOVA for repeated measures: p = 0.507). On average, a slight decrease of the serum creatinine was found.All patients remained in their routine dialysis-program. 18 out of 100 died during the next three months after the procedure. Conclusion The study revealed that the coronary angiography using Iodixanol as iodinated contrast medium did not result in an increase of serum creatinine, which was drastically elevated in these patients before application of the iodinated contrast medium.

Introduction Concomitant mitral-regurgitation (MR) is frequently observed in patients undergoing trans-catheter aortic valve implantation (TAVI). The predictive value of MR etiology remains to be elucidated. Methods 600 patients with coincidental MR (≥moderate) undergoing TAVI were categorized according to a modified Carpentier classification [Groups: no/mild MR, n = 477; left atrial (LA) functional MR, n = 18; MR due to left ventricular dilatation, n = 29; degenerative MR, n = 50; MR with restricted leaflet motion n = 26]. MR improvement and patient outcome was compared among the groups in a retrospective analysis. Results MR regression was most pronounced in patients with restricted leaflet motion after 6 months, although a significant improvement was observed in all subgroups. MR relief was predominantly observed within the first 30 days after TAVI. Only patients with restricted leaflet motion experienced further improvement thereafter.In the entire cohort a total of 15 strokes (2.5%) during the first 30 days after TAVI were observed, with the highest incidence in the LA functional cohort (3 events, 17%; p = 0.008). In multivariate analysis, organic etiology was associated with an increased 1-year mortality.In conclusion, despite significant MR regression in all MR groups, some individuals may require additional mitralvalve repair after TAVI. According to our data the timing of these procedures should be based on the underlying MR etiology. The Carpentier classification in patients with coincidental MR undergoing TAVI for severe AS may also have prognostic implications as we found an increased incidence of strokes in our LA functional cohort and a worse mortality rates in organic MR.

Background Transcatheter foramen ovale closure (TPC) has emerged as a potential treatment option for patients with cryptogenic strokes and persistent foramen ovale (PFO). However, previous randomized controlled trials could hardly demonstrate any benefit compared to medical treatment (Med-Tx). Recently new data have become available which may change current practice of transcatheter PFO closure. Methods A systematic review and meta-analysis comparing TPC and Med-Tx based on all available multicentric randomized controlled trials was performed. The primary outcome of interest was the recurrence of stroke in both groups. Results Five studies met the inclusion criteria with 1829 patients in the TPC and 1622 in the Med-Tx group. The median follow-up was 4 years. In the intention-to-treat analysis we found a statistically significant relative risk reduction in recurrence of strokes in the TPC group compared to the Med-Tx group (pooled hazard ratio (HR): 0.32; 95% CI: 0.13–0.8; P = .018). Excluding one study due to potential publication bias resulted in a pooled HR of 0.48 (95% CI: 0.25–0.91, P = .024). Patients younger than 45 years of age (pooled HR: 0.35; 95% CI: 0.16–0.75; P = .007) and those with moderate to severe shunt (pooled HR: 0.28; 95% CI: 0.14–0.55; P < .001) were more likely to benefit from closure. Conclusion According to our meta-analysis TPC plus antiplatelets was superior in terms of stroke prevention when compared to Med-Tx. Furthermore, patients with moderate to severe shunts and those younger than 45 years of age were found to benefit most from TPC.

The dental pulp is an important soft connective tissue which is able to produce dentin over time as a reaction on external stimuli. It also maintains the biological and physiological vitality of the dentin. Due to this the pulp is essential for teeth homeostasis. However, dental caries is still one of the most prevalent health problems in dentistry and therefore, one major cause for early loss of the dental pulp vitality and subsequent tooth extractions. Meanwhile the potential for successful pulp regeneration therapy is increasing due to advances in the field of regenerative endodontics. Thus, adequate experimental animal models are required for testing and validating these new regenerative therapies. Rodents and rats in particular, are relevant models for experimental periodontal research. The breeding and housing costs of rats are relatively low facilitating studies with sufficient numbers for statistical analysis in comparison to bigger sized mammals like beagle dogs, miniature pigs or monkeys. Additionally, rat molar teeth and pulps are characterized by similar anatomical, histological, biological and physiological features to human teeth. Essential biological reactions of the pulp tissue and the interaction during the different stages of wound healing of rat molar teeth are comparable to that of other mammals. However, despite of the multiple research activities in the field of regenerative endodontics and the above mentioned advantages of the rat model only rare in vivo studies are published. Therefore, the presented study aimed to introduce the rat molar teeth as a valid model for studying dental pulp stem cell based endodontic tissue regeneration. Human dental pulp stem cells were implanted into the pulp of immunodeficient rats (RNU rats). Cell growth was supported by a collagenous membrane, which was applied on top of the cells after implantation. After closing the pulpal cavity with a light-polymerisable resin human dental pulp stem cells were able to maintain cell viability in the rat molar pulp niche for at least three weeks. This demonstrated the suitability of immunodeficient RNU rats for non-autologous dental stem cell based endodontic tissue engineering approaches.

The Laser Doppler technique (Laser-Doppler-Fluxmetry, LDF), a noninvasive method to estimate skin blood flow (LDF), is frequently used in research and clinical routine [1]. Here, the measurements were carried out with a new Laser Doppler system, the DOP-system, which allows to measure frequency spectra in four different frequency windows according to the velocities in venules (low velocity), capillaries (low to medium velocities), and in arteries (with high and very high velocities). However, the diagnostic reliability or the effectiveness of the LDF has not yet been evaluated sufficiently, which is indispensable, where medical diagnostics and therapy controls are concerned. For a valid interpretation of LDF values of individual patients, the knowledge of the reference range and the variability of the measured parameters is required.In four successive studies the reference range (62 apparently healthy subjects), the circadian variability (8 subjects), the variability from day-to-day (6 subjects) and over one year with monthly measurements (6 subjects) were evaluated.With the knowledge of the reference range, microcirculatory disorders can now be diagnosed using the DOP method. Following a standard measurement procedure there was no dependence of the measured data on the day or season of measurement.

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%.

Recombinant human erythropoietin (rHuEPO) is an agent commonly used by athletes with the aim to improve performance in endurance sports. However, the scientific community continues to debate the risks, benefits and its mechanism of action when used as a doping agent. This paper provides a brief overview on the pros and cons of rHuEPO use, as discussed by a group of scientist with diverse background, at the 17th Conference of the European Society for Clinical Hemorheology and Microcirculation in Pecs, Hungary. Among multiple topics, panel members challenged the common belief that the increased circulating hemoglobin concentration is the simple key to the improved sporting performance. Rather, hemorheologists developed the concept of optimal hematocrit (Hct), a Hct value that represents the optimal balance between the oxygen transport capacity of blood and blood viscosity. While guideline-directed transfusion therapy is advantageous under pathological conditions, such as severe anemia related to chronic kidney disease, its beneficial effects on endurance in healthy athletes remains questionable. Further studies are warranted in the field evaluating the effects of rHuEPO that are independent of increasing hemoglobin concentration, such as peripheral vasodilation and tissue metabolic changes.

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.

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.

There is a widely recognized need to improve the performance of vascular implants and external medical devices that come into contact with blood by reducing adverse reactions they cause, such as thrombosis and inflammation. These reactions lead to major adverse cardiovascular events such as heart attacks and strokes. Currently, they are managed therapeutically. This need remains unmet by the biomaterials research community. Recognized stagnation of the blood-biomaterial interface research translates into waning interest from clinicians, funding agencies, and practitioners of adjacent fields. The purpose of this contribution is to stir things up. It follows the 2014 BloodSurf meeting (74th International IUVSTA Workshop on Blood-Biomaterial Interactions), offers reflections on the situation in the field, and a three-pronged strategy integrating different perspectives on the biological mechanisms underlying blood-biomaterial interactions. The success of this strategy depends on reengaging clinicians and on the renewed cooperation of the funding agencies to support long-term efforts.

Within the hemocompatibility testing portfolio of medical devices a range of dynamic models were established in recent years. In contrast to the static hemocompatibility testing method the dynamic models allow considering the impact of hemorheological and hemodynamic blood characteristics on the hemocompatibility of medical devices. Unfortunately the EN DIN ISO 10993-4 for the biological evaluation of medical devices for interaction with blood gives no hints towards the period of time during which the medical devices should be exposed to the blood in these tests. To examine whether different exposure times impact the comparability of hemocompatibility test results low density polyethylene (LD-PE) tubes and nitinol stents were tested exemplarily in a closed loop model for changes of the fibrinogen content, the prothrombin time, the thrombin time, and the C5a activity after 30 and 90 min exposure to the blood. Low density polyethylene was used as negative control because it is one of the European reference materials for hemocompatibility testing. After 90 min blood exposure to the LD-PE tubing and the nitinol stents the prothrombin time was significantly longer and the fibrinogen content significantly lower (p < 0.05) than after 30 min. In contrast the thrombin time and the C5a were comparable after 30 and 90 min blood exposure time. These results might recommend to an initial 30 min exposure time, which is followed by a 90 min exposure time in cases of unclear results.

Trans-catheter pulmonary valve implantation (TPVI) has become the treatment of choice in most congenital heart disease patients with degeneration of a previous right ventricular outflow tract (RVOT) repair. Since the life expectancy of this patient cohort is improving, there is an increased demand of these procedures. Efficacy and safety have been demonstrated for the Medtronic Melody and the Edwards Sapien valves, although there is still a paucity of data and no consistent procedural recommendations are available.

Die Magnetokardiographie (MKG) ist eine beruhrungs- und strahlungsfreie, nichtinvasive Methode zur Erfassung der elektromagnetischen Aktivitat des Herzens. Theoretische Gesichtspunkte und vergleichende Untersuchungen deuten auf einen unterschiedlichen Informationsgehalt von MKG und Elektrokardiogramm (EKG) hin. Obwohl eine Vielzahl von Fragestellungen der kardialen Elektrophysiologie und Pathophysiologie durch magnetokardiographische Untersuchungen beantwortet werden kann, ist die Methode immer noch weitgehend unbekannt. Im Vergleich zum EKG ist der Betrieb eines Magnetokardiographen durch Verwendung supraleitender Sensoren mit der Notwendigkeit zur Kuhlung mit flussigem Helium und aufwendiger magnetischer Abschirmung um ein Vielfaches teurer und nicht am Patientenbett verfugbar. Der Gewinn an diagnostischer Information lasst den Aufwand jedoch als gerechtfertigt erscheinen, da die Sensitivitat fur ischamisches Myokard sowohl in Ruhe als auch unter Belastung deutlich hoher ist als die des EKG. Im Hinblick auf die Risikostratifizierung fur den plotzlichen Herztod erlaubt die Magnetfeldanalyse moglicherweise eine genauere Indikationsstellung fur die prophylaktische Defibrillatorimplantation. Die raumliche Auflosung ist hoch genug fur eine nichtinvasive Lokalisation arrhythmogener Foki, was die Methode insbesondere fur das Management von Vorhofflimmerablationen interessant macht. Prospektive und ausreichende klinische Daten fehlen jedoch bisher weitgehend. Es gibt ausreichend Raum fur Fantasien uber weitere Fragestellungen der klinischen Kardiologie, die mit der MKG beantwortet werden konnen.

Heart failure patients are clinically characterized by extreme cardiomegaly, breathlessness, fluid retention and an early onset of fatigue. Studies have shown generalized restricted blood flow in those patients. Furthermore animal experiments proved an impaired blood flow and a diminished oxygen supply of the skeletal muscle in animals with chronic heart failure. Patients with chronic heart failure are limited to the extent of their ability to regulate their arterial pressure, especially in physical activity. It is however unclear in what way restriction of blood flow in the main arteries correlates with those in capillaries and to what extent. In this study it was examined the depth of capillary circulatory restriction as well as the disregulation of oxygen partial pressure in skeletal muscle in rest and stress conditions, in patients with terminal heart failure.

During extracorporeal circulation (ECC) controlled hypothermia is a common method of myocardial protection due to a reduction of the myocardial oxygen consumption. Although the beneficial aspects of hypothermia on the myocardial metabolism have been widely demonstrated the effect of hypothermia on the myocardial oxygen tension (PmyO2) is unclear. For this reason the PmyO2 of German Landrace pigs (male, three months of age) during ECC was analysed under mild hypothermia (32°C, n = 6 pigs) and under normothermia (n = 10 pigs, control group) within a time period of 23 min (1400 sec). Flexible invasive Clark type microcatheters were used to measure the PmyO2 in the beating heart. During normothermal ECC a continuous PmyO2 increase from 36.5 ± 15.8 mmHg to 52.6 ± 27.2 mmHg (+44.1%) after 1400 sec was measured (p = 0.02). In contrast, mild hypothermia caused a continuous PmyO2 decrease from initially 46.9 ± 17.5 mmHg to 36.7 ± 20.8 mmHg (−21.8%, p < 0.013) in the test period. Electrocardiography revealed no signs of ischemia or arrhythmia during normo- and hypothermic ECC. It seems obvious that mild hypothermia results in a reduction of the oxygen transfer to the myocardial cells and that this effect outweighs the beneficial effects of hypothermia in the myocardium which are related to reduced oxygen consumption. However, in mild hypothermia oxygen supply to the myocardium remained sufficient for normal myocardial function.

Minipigs are frequently used for scientific research as they are easy to handle and the dimensions of their vascular system do not change after 20 months of age. Although surgical interventions under anaesthesia are often performed in the supine position the effects of this positioning on lung functionality in minipigs have not been systematically described. This study aimed to analyse the influence of supine positioning on the macrostructure of the lung and the pulmonary density by the use of computed tomography imaging in pre-adult Gottingen minipigs. Twelve pre-adult female minipigs were used in the study and lung density was investigated in both the prone and the supine positions. The time between the scans in prone and supine positions was less than 5 minutes (296 ± 6 sec). In the prone position lung density did not differ between the dorsal and ventral part of the lung (-641 ± 72 Hounsfield units [HU]). However in the supine position there was a ventrodorsal gradient of decreasing density (ventral part of the lung: -497 ± 106 HU, dorsal part of the lung: -723 ± 51 HU). The changes in lung density were not accompanied by changes in lung volume (829 ± 191 ml). These results suggest an influence of the body position on the ventilation/perfusion (V(A)/Q) matching of the lung which could possibly result in lowered lung oxygenation as well as in an increased heart activity in the supine position. Additionally, due to the steep course of the vena cava caudalis from the caval foramen in the diaphragm across to the heart (in contrast to the more shallow course in the prone position) the activity of the heart necessary to pump the venous blood to the right atrium has to be higher in the supine position than in the prone position. In pigs the capacity of the heart to increase frequency is limited due to a diastolic/systolic (D/S) ratio

Objective The study aimed to test a Nitinol®-based vein cuff model for external banding valvuloplasty. Method In 12 adult minipigs, the vena jugularis externa was covered for 42 days by a cuff with an inner diameter adapted to the outer vein diameter in supine position. By changing from supine into prone position hypostatically vein dilation was induced to simulate varicose vein dilation. Cuff position and the inner diameter of the vein lumen under the cuff were examined by computer tomography scanning. Also, histological analysis of the vein wall within the cuff was performed. Results The preset tubular shape of the cuff and the cuff position did not change in both prone and supine position, but due to fibrosis the luminal vein diameter within the cuff was decreased ( P < 0.01) already after 21 days. Conclusion A foreign body response resulted in a fibrous capsule covering the cuff which might limit cuff functionality.

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.

In cardiac surgery the substitution of lost blood volume by plasma substitutes is a common therapeutical approach. None of the currently available blood substitutes has a sufficient oxygen transport capacity. This can limit the functional integrity of the myocardium known as highly oxygen consumptive. The study was aimed to get information about the minimal hematocrit, also known as critical hematocrit (cHct), which guarantees a stable and adequate oxygen partial pressure in the myocardium (pO2). In adult female pigs (n = 7) the hematocrit was reduced by isovolemic blood dilution with an intravenous infusion of isotonic 4% gelatine polysuccinate solution, The substituted blood volume ranged between 3000 ml and 7780 ml (mean: 5254 ± 1672 ml). In all animals the pO2 of the myocardium of the beating heart and of the resting skeletal muscle increased until blood dilution resulted in a Hct decrease down to 15%. Further blood dilution resulted in a decrease of the pO2. Only after the Hct was < 10% the pO2 was lower than before blood dilution and accompanied by a lethal ischemia of the myocardium. These data indicate a cHct of about 10% in the pig animal model.

PURPOSE It was the aim of our study to establish the extent to which contrast enhancement with SonoVue(R) in combination with quantitative evaluation of contrast-medium dynamics facilitates the detection of malignant hepatic tumors. MATERIALS AND METHODS One hundred patients with histologically confirmed malignant or benign hepatic tumors (maximum size 5 cm) were analyzed. We used a high-end ultrasound machine (Logic 9, GE Healthcare, Milwaukee, WI, USA), with a multifrequency curved array transducer (2.5 - 4 MHz), Contrast-enhanced ultrasound (bolus injection 2.4 mL SonoVue(R)) was carried out with the intermittent breath-holding technique. Native vascularization was analyzed with power Doppler sonography. The contrast-enhanced dynamic ultrasound investigation was carried out with contrast harmonic imaging in the true detection mode during the arterial, portal venous and late phases. The mechanical index was set at 0.15. Perfusion analysis was performed by post-processing of the raw data (time intensity curve [TIC] analysis). Biphasic 16- or 64-slice multislice computed tomography served as reference method in nearly all cases. RESULTS One hundred patients with 59 malignant (43 colon, 5 breast, 2 endocrine metastases, 7 hepatocellular carcinomas and 2 kidney cancers) and 41 benign (12 circumscribed fatty changes, 2 abscesses, 7 focal nodular hyperplasias, 5 complicated cysts and 15 hemangiomas) tumors were included. The CT classification was true positive in 71 of 92 patients, false negative in 8 cases, and in 13 cases no final diagnosis was possible; sensitivity was 96.7 % and specificity was 71.4 % for CT. The quantitative contrast harmonic imaging ultrasound classification was true positive in 98 of 100 patients and false negative in 2 cases; the sensitivity was 98.6 % and the specificity was 96.6 %. The Fisher test showed a significant difference at p < 0.05. No investigator-dependency was noted. CONCLUSION In our study contrast-enhanced ultrasound was more accurate than multislice computed tomography in the prediction of malignancy and benignity of liver tumors.

While structure and function of precapillary sphincter cells were assured in skin capillaries it is unclear whether segmental reduction of capillary lumina can occur in human capillaries. It has been shown that endothelial cells are able to exert dynamical reactions. Since the first description of the vascular endothelium a great variety of findings were described concerning the active role of capillary endothelial cells in regulation of the capillary lumen applying intravital microscopy. The intravital microscopy was performed in the framework of an observational study to document the long-term stability of capillaries in healthy subjects over many years. In the second year one of the participants showed remarkable changes in capillaries compared to recent recordings. Control recordings were performed 1, 3, 4, 5 and 20 h after the initial examination — until a complete normalization of the capillaries occurred. This case report is documenting for the first time clearly that extreme luminal narrowing of long segments of cutaneous capillaries can also appear in humans, in this case restricted exclusively to the venular leg of the capillaries. Different from the reductions of the capillary lumen induced by electrical irritation in frogs which lasted only for seconds, the capillary lumen narrowing in this case lasted considerably longer, almost over a whole day. It is important to note that the demonstrated findings did not occur in all capillaries and it remains unclear whether such findings are restricted to skin capillaries or might occur also in other regions of the body or even systemically. It could be demonstrated clearly, however, that segmental narrowing of capillary lumina can occur in humans possibly leading to a temporary stillstand of perfusion.

Objective: Magnetocardiography (MCG) as a noninvasive, noncontact and risk-free diagnostic method predicts ischemic coronary artery disease (CAD) in patients with acute chest pain at admission with high accuracy. However, it remains unclear whether MCG findings can add prognostic information. Method: A cohort of 402 consecutive patients presenting at the intensive care unit (ICU) with acute chest pain without ST segment elevation (NSTEMI) were included in a prospective registry. In order to prove the prognostic value of MCG a head-to-head comparison of the admission MCG, ECG, TnI, and ECHO tests was made. Results: In 43 patients (10.7%) the MCG could not be analyzed due to insufficient signal-to-noise ratio. Complete follow-up over a period of up to 3 years was obtained in 355 out of the 359 patients (98.9%). Age at admission was 67.2 ± 10.3 years, 59.7% males. In the group of patients with an abnormal MCG at admission, 43 out of 249 patients (17.3%) died in the follow-up period, while in the group of patients with a normal MCG at admission only 4 out of 106 patients died (3.77%). The relative risk was 4.58 (95% confidence intervals: 1.68–12.42). A multivariate regression analysis revealed the highest mortality risk for patients with diabetes mellitus and an abnormal MCG at admission (RR = 18.0; 95% CI: 2.49–133.3). Conclusion: Resting MCG at hospital admission predicts 3-year mortality in patients presenting with acute chest pain without ST segment elevation in the ECG. MCG seems to be valuable in identifying chest pain patients at highest risk.

Introduction: The introduction of phosphodiesterase-5 inhibitors as sildenafil, tadalafil, or vardenafil, has tremendously improved the treatment of erectile dysfunction. Patients with the common comorbidity of cardiovascular disease and erectile dysfunction, however, are at risk for critical hypotension in case of self-treatment of cardiac angina with nitrates after the intake of a phosphodiesterase-5 inhibitor. Methods: We evaluated the safety of 5 mg sublingual nitrendipine after pre-treatment of 8 healthy male volunteers (42.1 ± 9.6 yrs) with 20 mg tadalafil. Randomly four different protocols were compared using six hours blood pressure recordings: (1) baseline, (2) 20 mg tadalafil, (3) 5 mg nitrendipine, and (4) 20 mg tadalafil + 5 mg nitrendipine. Results: The blood pressure was not significantly affected by tadalafil. Nitrendipine lowered the systolic blood pressure significantly by -1.91 mmHg (p = 0.0079). The co-medication of 20 mg tadalafil + 5 mg nitrendipine lowered the blood pressure significantly by -2.86 mmHg (p < 0.0001). There was no statistically significant difference between tadalafil and nitrendipine (p = 0.598). Relevant hypotension (systolic blood pressure of

Xantinole nicotinic acid (NA) dose dependently lowers plasma levels of atherogenic lipoproteins and increases blood flow through vasodilation. The aim of this study was to evaluate the effect of NA on cutaneous microcirculation in patients with coronary artery disease and hyperlipidemia. In this open pilot study, five men and three women (74.2 ± 9.1 yrs; 81.4 ± 7.9 kg; 171.6 ± 7.0 cm) with angiographically proven coronary artery disease and hyperlipidemia were included. Nailfold capillary microscopy was used for measurements of erythrocyte velocities at rest and after three minutes of ischemia, before and one hour after intake of 1000 mg of NA. The blood pressure (120 ± 12/73 ± 8 mmHg vs. 113 ± 10/72 ± 5 mmHg; p = 0.19/0.83) and the heart rate (72 ± 8/min vs. 70 ± 7/min; p = 0.38) remained unchanged. The mean capillary red blood cell velocity at rest (υ RBc ; 0.27 ± 0.23 mm/s vs. 0.32 ± 0.18 mm/s; p = 0.089) and the time to maximal post ischemia erythrocyte velocity (t peak ; 21.0 ± 7.9 s vs. 24.3 ± 15.5 s; p = 0.49) did not change. The maximal post ischemic erythrocyte velocity (υ maxRBC ; 0.93 ± 0.33 mm/s vs. 1.19 ± 0.19 mm/s; p = 0.0096) raised slightly but significantly, the duration of post-ischemia hyperemia (DpH; 101 ± 16 s vs. 127 ± 15 s; p = 0.0005) increased markedly. One patient reported about flush in the whole body. The administration of 1000 mg of NA resulted in a significant improvement of the cutaneous microcirculation in patients with coronary artery disease and hyperlipidemia.

Purpose: The use of clopidogrel is standard in interventional cardiology. Haemorrhage occurs in some patients, which implies a need for a non-transfusional therapy. Desmopressin showed its efficacy as an antidote of acetylsalicylic acid. In this trial the effects of desmopressin on platelet glycoproteins and the platelet's ability to aggregate under the influence of clopidogrel are studied. Methods: The trial was conducted as an open, prospective, single-centre, randomised pilot study with n = 17 healthy volunteers in a parallel-group design. 1 h after an oral loading dose of 375 mg clopidogrel the effects of a single-dose of 300 µg of Octostim ® nasal spray (n = 9) on platelet aggregation, activity of platelets on the density of membrane-bound receptors are measured. Results: Ristocetin cofactor and platelet reactivity rose significantly after the administration of Octostim ® nasal spray with 31.9% and 5.3%, respectively (p = 0.0329; p = 0.0414). The ADP-induced platelet aggregation increased after the admin- istration of Octostim ® nasal spray by approximately 20% (p = 0.0564). The fraction of CD62- and CD63-positive platelets did not change after clopidogrel nor after desmopressin (p = 0.4203; p = 0.6774). The density of GPIIb/IIIa receptors per platelet did not change after desmopressin (p = 0.9652). The density of GPIb/IX receptors per platelet rose after desmopressin without reaching the level of significance (p = 0.0802). In the desmopressin group alone the receptor density rose by 5.5% (p = 0.0783). Conclusion: The administration of desmopressin improved the primary haemostasis when given in addition to a clopidogrel therapy. Patients undergoing a heart catheter procedure with clopidogrel might benefit from the use of desmopressin when having a bleeding episode.

Background Exercise electrocardiography is an imperfect test for the detection of coronary artery disease (CAD). Magnetocardiography detects cardiac electrical disturbances associated with myocardial ischemia. We prospectively investigated the accuracy of high-dose dobutamine stress magnetocardiography (DS-MCG) and simultaneous electrocardiography (DS-ECG) for the detection of significant CAD. Methods 100 patients with an intermediate pre-test probability for CAD underwent DS-MCG using a multichannel magnetometer prior to invasive coronary angiography. Patients were examined at rest and during a standard dobutamine-atropine scheme. Significant reduction of epicardial current strength/density during stress, reconstructed from the magnetic field map and superposed on a virtual heart model indicates myocardial ischemia. A 12-lead DS-ECG was recorded simultaneously. Significant coronary artery stenosis was defined as > or = 70% of lumen reduction. Results Without beta-blocker all 100 patients reached the targeted heart rate. The image quality of DS-MCG and DS-ECG was sufficient for analysis in all patients. In 19 patients CAD was ruled out angiographically. Thirty two or seven patients revealed coronary artery stenoses of 30-49% or of 50-69%, respectively. In 42 patients we found significant stenoses of > or = 70%. In 41 of these patients DS-MCG revealed myocardial ischemia. The sensitivity of DS-MCG and DS-ECG for the detection of significant coronary artery stenosis was 97.6% and 26.2%, the specificity of DS-MCG and DS-ECG 82.8% and 82.8%, respectively. Conclusions DS-MCG can be performed with a standard dobutamine/atropine stress protocol. DS-MCG yields a significantly higher accuracy for the detection of significant coronary artery stenosis than DS-ECG.

Purpose: To examine how a one-time bolus injection of radiographic contrast media (RCM; iodixanol 320 and iomeprol 350) into the left coronary artery of six pigs affects tissue oxygen tension in the artery's supply area (pO2 LAD) compared to a 0.9% sodium-chloride (NaCl) bolus. Material and Methods: Each animal received a total of three boluses: one iodixanol, one iomeprol, and one NaCl (10 ml each). The radiographic contrast media and NaCl boluses were randomly assigned, and pO2 profiles were recorded. Results: 26.7±16.4 s after iodixanol injection, pO2 LAD had declined by 3.5% from 42.2±5.6 mmHg to 40.7±5.9 mmHg ( P = 0.0357). After 53±16.7 s, the initial value was restored. The pO2 LAD was 41.9±7.4 mmHg before iomeprol injection, and, 303.3±58.9 s after injection, pO2 LAD had declined by 13.1% to 36.4±7.5 mmHg ( P = 0.0001). After 577±22 s, the initial value was restored. The bolus application of an isotonic NaCl solution resulted in no effect on pO2 LAD. Immediately after injection, it increased by 3%. In the supply area of the right coronary artery and the peripheral skeletal muscle, no effect of the RCM or NaCl on tissue oxygen tension was observed. Furthermore, no effect on tissue temperature, heart rate, systolic and diastolic blood pressure, or cardiac output per minute occurred. Conclusion: The injection of RCM in a coronary artery can result in a significant local contrast-medium-induced microcirculation disorder. The high viscosity of iodixanol led to a very short-term insignificant effect on the microcirculation, while iomeprol induced a slight time-delayed pO2 decrease, which might be caused by the rigidification of erythrocytes. In comparison to a previous study with iopromide, the influence of iodixanol and iomeprol on myocardial oxygen tension was markedly less pronounced.

Eun-Seok Shina, Soe Hee Anna, Johannes Brachmannb, Yat-Yin Lamc, Friedrich Jungd and Jai-Wun Parka,∗ aDepartment of Cardiology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Korea bCoburg Hospital, 2nd Medical Department, Coburg, Germany cPrince of Wales Hospital, Chinese University of Hong Kong, Hong Kong dInstitute for Clinical Hemostasiology and Transfusion Medicine, Saarland University, Homburg/Saar, Germany

Background: Blood viscosity has a role in modulating cardiovascular homeostasis; changes in this parameter have been associated with cardiovascular mortality and morbidity. However, it remains unclear whether these changes are (1) involved in the pathophysiology of disease, (2) an epiphenomenon, or (3) the expression of counterregulatory mechanisms. We report data on the normal values of blood viscosity and its association with cardiovascular risk factors, prevalent cardiovascular disease, and blood pressure in a large population-based cohort study. Methods and results: Viscosity was calculated using validated formulae and its associations were explored in 15,010 participants (mean 55.0, min–max: 35–74 years old; 49.5% women) from the Gutenberg Health Study as well as in a subgroup of 3223 subjects (61.1% women, mean age 49.2, min–max 35–74 years old) without risk factors or self-reported cardiovascular disease. Age- and gender-adjusted mean values for viscosity were defined. Regression models showed a relationship between classical risk factors and blood viscosity measures; the overall R2 of the multiple linear regression model was however as low as 0.067 and 0.049 for high and low shear stress viscosity, respectively. After correction for cardiovascular risk factors, there was a very mild association between viscosity and prevalent coronary artery disease and heart failure. Systolic, mean and diastolic blood pressure increased with increasing blood viscosity after correction for age and gender. Conclusions: We provide reference values for viscosity in a population-based cohort. Blood viscosity decreases in older subjects and shows a very mild association with cardiovascular risk factors and prevalent disease in our cohort. There is a linear positive association between viscosity and blood pressure.

Die chirurgische Behandlung des Vorhofflimmerns durch das klassische MAZE-Verfahren oder andere Ablationsmethoden resultiert in Konversionsraten in den Sinusrhythmus von 50–90%. Bis heute liegen keine Ergebnisse zum Einfluss der Ablationsbehandlung auf die Mortalitat vor. In einer prospektiven Registerstudie wurden 210 konsekutive Patienten mit permanentem Vorhofflimmern hinsichtlich peri- und postoperativer Mortalitat nach herzchirurgischen Eingriffen uber 2 Jahre nachverfolgt. Bei 111 Patienten wurde eine endokardiale Mikrowellenablation durchgefuhrt, 99 Patienten wurden ohne Ablation operiert. In der Ablationsgruppe starb ein Patient (0,9%) perioperativ, weitere sieben starben wahrend des ersten Jahres (6,3%) und neun wahrend des zweiten Jahres des follow-ups (8,1%). In der Kontrollgruppe verstarben funf Patienten perioperativ (5,1%), 12 Patienten starben innerhalb des ersten Jahres (12,1%) und 22 innerhalb des zweiten Jahres des follow-ups (22,2%). Daraus ergab sich eine signifikant hohere Mortalitat in der Kontrollgruppe gegenuber der Ablationsgruppe (Log-Rank-Test: p=0,0051). Die Ergebnisse dieser Registerstudie zeigen, dass unter Patienten mit permanentem Vorhofflimmern die Mortalitat nach herzchirurgischen Eingriffen mit Mikrowellenablation signifikant geringer ist als bei vergleichbaren Eingriffen ohne Ablationsbehandlung. Der deutliche Mortalitatsunterschied basierte vor allem auf den typischen Folgen des Vorhofflimmerns (thrombembolische Komplikationen, kardiale Arrhythmien und Blutungen unter Antikoagulanzientherapie), welche in der Ablationsgruppe seltener auftraten.