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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.

Several methods are available today for the investigation of microcirculation in animal models, but they can be invasive and time-consuming depending on the area investigated. In particular, non-invasive methods that can be conducted rapidly and without dye or tracer injections are in demand. The cutaneous microcirculation can be easily studied in the dorsal corium limbi of the third toe of the porcine forelimb using intravital microscopy - analogous to nail fold capillary microscopy in humans. The capillary microscopy system consists of a reflected-light microscope with a cold light source, green and infrared filters and a video camera. The video sequences were recorded using the image capture system Framegrabber (Imagenation PXC-200) and a PC (with an Intel Core 2 Duo processor, 1024 MB RAM, 160 GB hard disk, Windows XP Pro), and stored via a DVD recorder (Panasonic LQ-MD800). Quantification of capillary erythrocyte flow velocities was performed using the computer-assisted image analysis system Cap Image Version 8.5 which includes a movie tool as a video sequence storage medium. The method allows estimation of capillary density and tortuosity as well as capillary circulation in the anesthetized pig within a few minutes. First measurements were made after anesthesia induction followed by further measurements during anesthesia maintenance (3 minutes each). No differences in capillary circulation were found. The present method is thus very well suited for long-term microcirculation measurements in pigs, e.g., to evaluate therapeutic interventions in the ischemic limb model.

The intra-arterial application of radiographic contrast media (RCM) can induce decreases of blood flow velocity in downstream capillaries as well as a decrease in the tissue oxygen tension. It is unclear whether changes in endothelial cell morphology contribute to the observed microcirculatory disorders. Four RCMs (Iodixanol320, Iohexol350, Iopromide370, and Imeron350) were added to the culture medium of human umbilical venous endothelial cells (HUVEC) and used for short-term incubation studies of these cells. Addition of Iohexol ( p = 0.6377) and Iodixanol ( p = 0.6309) did not affect the HUVEC height 1.5 min after incubation in the modified cell culture media supplemented with 30% v/v of the respective RCM. Strong buckling and increased endothelial height appeared after incubation in Iopromide-supplemented medium (the cell height increased by 95% compared to cells incubated under control conditions; p = 0.0065). Addition of Iomeprol-supplemented medium caused an increase by 61.6% compared to cells incubated under control conditions; p = 0.0051. After 5 min of incubation in any of the RCM-supplemented media, there was no difference in HUVEC height in comparison to incubation in control standard culture media (each p value > 0.05). The tremendous buckling caused by Iopromide and Iomeprol, coinciding with an echinocyte formation of erythrocytes might be the reason why a bolus injection of Iopromide in vivo into the left coronary artery was followed by a 50% decrease of oxygen partial pressure in the supplied tissue.

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.

Various radiographic contrast media (RCM) significantly influence the morphology of erythrocytes, especially the formation of echinocytes [Scand. J. Clin. Lab. Invest. 35 (1975), 1-43; Microvasc. Res. 60 (2000), 193-200; Herz 23 (2003), 35-41]. Microscopic studies, however, have shown that these changes of erythrocyte morphology are possibly reversible [Acta Radiol. 37 (1996), 214-217]. The aim of this study was to proof if the RCM-induced echinocyte formation can be reversed by a resuspension in autologous plasma. In this study four RCMs were tested (Iodixanol, Iohexol, Iomeprol and Iopromide). These RCM induced echinocyte formation (after suspension of erythrocytes in plasma/RCM mixtures for 10 min at 37 degrees C), which was reversible after resuspension in autologous RCM-free plasma (resuspension time 5 min at 37 degrees C). Especially for Iomeprol and Iopromide - the RCMs which induced the strongest echinocyte formation - an echinocyte reduction from 94.2% to 44.5% and for Iopromide from 80.6% to 50.4% occurred. The echinocyte formation was influenced by the type of RCM as well as by the RCM concentration. The same was true for the reversibility of echinocyte formation due to resuspension in autologous plasma (type of RCM: p

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.

Purpose To evaluate the extent to which Tissue Harmonic Imaging (THI) and spatial averaging (Sono-CT, Cross Beam) facilitate the diagnosis of lower leg venous thrombosis. Materials and methods In 100 cases of lower leg venous thrombosis, the conventional B-scan, THI, and ultrasonic CT technology (Cross Beam) in examinations using a multi-frequency transducer head (9 - 14 MHz, Logiq 9, GE) were compared during follow-up studies using compression sonography over at least 6 weeks. Two independent examiners performed digital image documentation (PACS connection) without modifying the gray level parameters optimized in the B-scan. A thrombosis was considered to be proven sonographically if at least one ultrasonic modality yielded findings reproducible in follow-up checks at a comparable site in accordance with both examiners. Results Thromboses in the V. tibialis posterior category (97 %) and the fibular category (81 %) were found most often, followed by muscular venous thromboses (48 %). Thromboses in the V. tibialis anterior category were rare (12 %). The procedure comparison showed an advantage for ultrasonic CT technology in terms of the demarcation of thromboses of the deeper veins (sensitivity 98 %), as compared to THI (sensitivity 87 %, specificity 91 %, PPV: 99 %) and the B-scan (sensitivity 81 %). Conclusion If a high-resolution linear transducer is used, THI and ultrasonic CT-Technology can facilitate the diagnosis of a lower leg venous thrombosis.

Aims Operative treatment of atrial fibrillation was initially performed as a maze operation in combination with mitral valve surgery or as a stand-alone procedure. The introduction of simplified ablation procedures led to the extension of operative atrial fibrillation treatment. Methods and results In 102 consecutive patients, endocardial microwave ablation was performed during coronary artery bypass surgery alone (n ¼ 42) or in combination with valve surgery (n ¼ 60). Patients were divided according to lesion line concept (the initial single lesion line concept connecting the pulmonary veins with the mitral valve annulus was replaced by a box lesion line concept including the left atrial appendage) and the complexity of the procedure. Patients were followed prospectively at 1, 3, 6, and 12 months post-operatively. Survival rate was 95.8% at 30 days and 88.5% after 1 year. There were no device-related complications. At all follow-ups, approximately 10% more of the patients with the first lesion line concept and coronary bypass operation alone showed stable sinus rhythm in contrast to the combination procedures. With the new lesion line concept, patients were significantly more often in sinus rhythm at 1-year follow-up (74% vs. 52%; P ¼ 0.0026). Conclusion Our results demonstrate that endocardial microwave ablation can be performed in combination with coronary artery bypass grafting with excellent conversion rate to sinus rhythm after 1 year without increasing the surgical risk for patients with permanent atrial fibrillation.

Background Although magnetocardiography (MCG) has been proposed as a non-invasive technique with high accuracy for functional diagnosis of myocardial injury, the validation of MCG against fractional flow reserve FFR in diagnosing coronary artery disease (CAD) has not yet been established. The goal of the study was to determine the diagnostic accuracy of MCG versus invasively determined FFR in patients with suspected or known CAD. Methods Forty seven patients with suspected CAD (35 men; mean age 69 years) who underwent coronary angiography and FFR measurement were enrolled. FFR ≤ 0.8 was considered to indicate significant myocardial ischemia. The change of ST-segment fluctuation score from rest to stress was calculated from the MCG. In addition, two blinded cardiologists assessed MCG images that were visualized by post-processing method, bull's-eye mapping. Results The best cut-off value of the percent change of ST-segment fluctuation score was -39.0% with sensitivity of 86.7% and specificity of 73.9%. Sensitivity, specificity, diagnostic accuracy, and the area under the receiver-operator characteristics curve of bull's-eye mapping for the detection of significant CAD were 90.5%, 92.3%, 91.5%, and 0.914 on a patient basis and 90.0%, 93.8%, 92.3%, and 0.919 by coronary territory, respectively. Conclusions MCG accurately detects functionally significant CAD as defined by using FFR, provides an assessment of ischemic status in agreement with the change of ST-segment fluctuation score, and accurately localizes the ischemic territory in bull's eye mapping. Therefore, MCG may provide an incremental value for prediction of myocardial ischemia non-invasively and safely in clinical practice with fast examination time.

Objective: Microwave ablation (MW) has been established as a safe and efficient procedure for the treatment of permanent atrial fibrillation (pAF) resulting in conversion to sinus rhythm (SR). For further improvement of clinical results, a new ablation line concept has been introduced. We present the first clinical results using this new concept in comparison with the results of previous ablation line concepts. Methods: Ablation lines were performed using microwave energy (Flex 2 and Flex 4 device). We compared two groups, including patients (pts) with mitral valve disease (MVD), coronary artery disease (CAD), and aortic valve disease (AVD). Group A included 137 patients, age 68.4 ^ 7.8, with ejection fraction 32‐ 80%, left atrial diameter 52.6 ^ 9.6 mm, suffering from MVD ðn ¼ 87Þ; CAD ðn ¼ 59Þ; or AVD ðn ¼ 17Þ with pAF for 6.5 ^ 9.2 years using the original ablation line concept. Group B included 112 patients, age 68.1 ^ 8.0, ejection fraction 20‐ 83%, left atrial diameter 53.1 ^ 8.7 mm with pAF for 6.8 ^ 7.0 years suffering from MVD ðn ¼ 72Þ; CAD ðn ¼ 33Þ or AVD ðn ¼ 36Þ performing a modified ablation line. Results: Survival rate of group A was 98.5% and 97.3% in group B. In the 6-month follow-up for group A, 62% of patients with MVD, 68% with CAD and 78% with AVD were in SR. For group B, 88% of patients with MVD, 78% with CAD and 85% with AVD were in SR. Conclusions: MW has become an efficient option with an excellent benefit/risk ratio for the treatment of pAF in patients with other cardio surgical disease. The modified ablation line concept in association with the introduction of a new ablation catheter resulted in a 10% higher success rate. Therefore we have established this new lesion line concept as our standard for microwave ablation.

Die Anzahl der chirurgischen koronaren Revaskularisationsoperationen stagniert und ist in den letzten Jahren sogar leicht rucklaufig. Die Frage ist, ob die Einfuhrung von Drug-eluting Stents das Operationsspektrum der Koronarchirurgie beeinflusst. Die Koronarchirurgie ist ein etabliertes Verfahren zur Behandlung der koronaren Herzerkrankung mit guten Ergebnissen. Studien belegen auch einen Vorteil zugunsten der Chirurgie im Verhaltnis zur interventionellen kardiologischen Therapie. Die jetzt zur Verfugung stehenden Stents neuester Generation, Drug-eluting Stents, zeigen in ersten Studien eine signifikant gunstigere Offenheitsrate als herkommliche Stents. Zurzeit gibt es aber keine Studien, die auch einen Vorteil gegenuber der chirurgischen Therapie bei gleicher Indikation erbringen. Es ist daher zum jetzigen Zeitpunkt nicht eindeutig zu beantworten, inwieweit das Spektrum der Koronarchirurgie durch Drug-eluting Stents beeinflusst wird.

ZusammenfassungZur Untersuchung der Plättchenfunktion wurde das von Wu und Hoak 1974 beschriebene Thrombozytenfunktionssystem von Grotemeyer 1983 modifiziert. Dieses System wurde gewählt, weil In-vitro-Manipulationen an den Plättchen nicht mehr notwendig sind und die Testauswertung maschinell (automatische Blutbildbestimmung) erfolgt. Die Testanordnung basiert darauf, dass Plättchenaggregate, die in vivo bestehen oder durch die Blutabnahme entstehen, durch Ethylendiamintetraessigsäure (EDTA) aufgelöst, durch EDTA-Formalin aber sofort fixiert werden. Ein Plättchenreaktivitätsindex nach Grotemeyer (PR) größer als 1,05 ist verdächtig, Werte über 1,2 sicher pathologisch. Der Test ist preiswert pro Messung (4 €) und schnell durchführbar (Blutbildmessungen und Index-Berechnung).Der PR wurde in drei prospektiven Studien zur Identifizierung von Non-Respondern bei der Sekundärprophylaxe (Hirninfarkt, PTCA bei kardialer Ischämie) arterieller Ischämien mit Azetylsalizylsäure (ASS) erfolgreich eingesetzt. So werden bei Hirninfarkt-Patienten bis 33% Non-Responder, bei Patienten mit kardialer Ischämie bis 18% erkannt. Des Weiteren finden sich in diesen Studien in der Gruppe mit pathologischem PR signifikant mehr thromboembolische Endpunkte als in der Gruppe mit normalem PR. In einer eigenen prospektiven Untersuchung zeigten sich signifikante Korrelationen zwischen PR zum RTH (Retentionstest Homburg) und PFA-100 beim therapeutischen Monitoring von ASS. Der PR scheint prädiktiv zur Beurteilung der Effizienz einer Therapie, aber nicht für die Erkennung bekannter unerwünschter Arzneimittelwirkungen von ASS (z. B. Überdosierung).

Aims: The aim of the study was to test the feasibility of the new Realtime Position Management mapping system for ablation of typical atrial flutter.

The aim of the present study was to evaluate the effects of ionic (ioxaglate) and non-ionic (iopromide) contrast media on haemostatic parameters ex vivo. In 40 patients undergoing coronary angiography, platelet function (platelet reactivity and serotonin concentration) and coagulation markers [thrombin-antithrombin III complexes, prothrombin fragments (F1+2) and the D-dimers] were measured. The use of an ionic X-ray contrast agent (XCA) (ioxaglate) in diagnostic cardiac catheterisation angiography is associated with lower thrombin generation and lower activation of the platelet system than when a non-ionic XCA is employed (iopromide). The results thus confirm the results of various in vitro studies and animal investigations.

The aim of the study is to evaluate the feasibility and safety of a new left atrial appendage (LAA) occluder. Twelve pigs were included. In 2 pigs the implantation process failed due to pericardial tamponade in 1 pig and device embolization in the other pig. The placement of the devices was controlled via TEE and fluoroscopy. After 6 weeks of implantation the hearts were explanted. The devices were found to be easy to deploy and showed a very good adaptation to the LAA tissue. Eight out of 10 pigs had full closure of the LAA directly after implantation. After six weeks, due to the self-modelizing properties of the device, all pigs had a full closure of the LAA. The macroscopic evaluation of the explanted hearts showed that all devices were securely integrated in LAA tissues. There was one case of mild pericarditis but no macroscopic signs of inflammation on the device surrounding endocardium. The explantation revealed that device loops had penetrated the LAA tissue in three pigs. However, no signs of bleeding, pericardial effusion, or other damage to the LAA wall could be detected and the pigs were in good condition with normal weight gain and no clinical symptoms. The Occlutech® LAA occluder achieved complete closure of the LAA in all pigs, and remained in the LAA, with benign healing and no evidence of new thrombus or damage to surrounding structures. Moreover, the uncompromised survival of all implanted pigs demonstrates the feasibility and safety of the device.

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.

Poly(ether imide) (PEI), which can be chemically functionalized with biologically active ligands, has emerged as a potential biomaterial for medical implants. Electrospun PEI scaffolds have shown advantageous properties, such as enhanced endothelial cell adherence, proliferation and low platelet adhesion in in vitro experiments. In this study, the in vivo behaviour of electrospun PEI scaffolds and PEI films was examined in a murine subcutaneous implantation model. Electrospun PEI scaffolds and films were surgically implanted subcutaneously in the dorsae of mice. The surrounding subcutaneous tissue response was examined via histopathological examination at 7 and 28 days after implantation. No serious adverse events were observed for both types of PEI implants. The presence of macrophages or foreign body giant cells in the vicinity of the implants and the formation of a fibrous capsule indicated a normal foreign body reaction towards PEI films and scaffolds. Capsule thickness and inflammatory infiltration cells significantly decreased for PEI scaffolds during days 7-28 while remaining unchanged for PEI films. The infiltration of cells into the implant was observed for PEI scaffolds 7 days after implantation and remained stable until 28 days of implantation. Additionally some, but not all, PEI scaffold implants induced the formation of functional blood vessels in the vicinity of the implants. Conclusively, this study demonstrates the in vivo biocompatibility of PEI implants, with favourable properties of electrospun PEI scaffolds regarding tissue integration and wound healing. Copyright © 2015 John WileySons, Ltd.

With the worldwide increase of atherosclerosis, the need for new engineered patient specific implants such as stents or vascular grafts is still emerging. Recently, very smooth poly(ether imide) (PEI) films were, based on their excellent hemocompatibility and compatibility with endothelial cells, suggested as potential biomaterial for cardiovascular applications. In atherosclerosis, immune mechanisms such as complement activation, but also cellular responses such as monocytes and neutrophils activation, can mediate the inflammatory response. Therefore, it is important that the implant material itself does not trigger the inflammatory response. Early immune mechanisms - e.g. macrophage activation, complement induction, generation of reactive oxygen species (ROS), and the secretion of inflammatory cytokines by leukocytes - could potentiate the inflammatory responses, and may thereby alter endothelial cells behaviour or facilitate platelet activation. Therefore, it is important to evaluate the immuno-compatibility of PEI-films. The PEI-films were fabricated from commercially available PEI, which was dissolved in dichloromethane and pulled out on a cleaned, smooth glass surface and subsequently, solvent residues were removed during the drying procedure. Using a murine macrophage reporter cell line possible material bound microbial contaminations and material intrinsic immuno-stimulatory properties were investigated. The macrophages were viable after adhering on the PEI-films and did not show signs of activation, indicating that the used PEI-film was free of microbial contaminations. To determine whether PEI-films induced complement activation, the release of C5a in pooled human plasma was analyzed. The detected C5a levels did not differ between PEI-films and tissue culture plates (TCP), which served as control material. Furthermore, in whole human blood, the generation of ROS as well as the cytokine production were investigated by flow cytometry and by multiplex bead arrays, respectively. The production of IL-6 and TNF-α as well as the generation of ROS by immune cells of the whole blood was not induced upon contact with PEI-films. The immunological evaluation of PEI-films revealed that no substantial activation of the investigated early immune mechanisms occurred. Altogether, this data demonstrate that PEI is immuno-compatible and from that perspective may be a suitable biomaterial for cardiovascular applications.

The polarization behavior of macrophages determines the clinical outcome after implantation of biomaterials. For- mation of classically activated macrophages (CAM) may result in cell fusion to form foreign body giant cells, which induce and support uncontrolled inflammatory responses and can cause undesired material degradation. In contrast, polarization into alternatively activated macrophages (AAM) is assumed to support healing processes and implant integration. The expression of matrix metalloproteinases (MMP) by the different macrophage subsets might play a crucial role for inflammatory and wound healing processes and may subsequently influence the implant integration. Therefore, it is of importance to characterize the MMP expression pattern by the different macrophage subsets. This knowledge could support the design of biomaterials in which specific MMP cleavage sites are incorporated allowing a controlled cell- mediated degradation of the material. However, it needs to be considered that the pure expression levels may not correlate with the enzymatic activity of the MMP, which depends on a variety of different parameters such as additional co-factors. For this reason, the differential MMP expression levels and the overall enzymatic activity of in vitro generated human non- polarized macrophages (M0), CAM, and AAM are analyzed in this study. While MMP-1, MMP-3, and MMP-10 showed the highest expression levels in CAM, MMP-12 was most strongly expressed by AAM. Interestingly, although various MMP were expressed at high levels in CAM, the enzymatic MMP activity was increased in supernatants of AAM cultures. The data presented here illustrate the importance to combine the measurement of MMP expression levels with the analysis of the enzymatic activity. The observed MMP-12 expression in combination with the higher enzymatic activity detected in AAM supernatants might motivate the design of biomaterials, whose structure could be modified by MMP-12 catalyzed reactions leading to interactive polymers.

In this study we investigated whether a disturbance in microcirculation is detectable in heart recipients with cardiac allograft vasculopathy (CAV) and severe hypercholesterolemia (n = 11) and in 7 heart recipients without CAV in comparison to patients with severe coronary artery disease (n = 49) and age-matched apparently healthy subjects (n = 100). For this purpose, the flow velocity of erythrocytes through cutaneous capillaries at the nail fold of the finger was measured under resting conditions. In addition, reactive hyperemia in the same capillaries after a 3-min ischemia was determined. Patients with CAV and severe lipid disorder showed a pathological reduction in mean capillary erythrocyte velocity under resting conditions with v(RBC) = 0.10 +/- 0.07 mm/s. The latter was significantly and relevantly lower than in patients with coronary three-vessel disease (v(RBC) = 0.46 +/- 0.35 mm/s). It was notable that under resting conditions temporary cessation of flow occurred in 8 of the 11 patients which did not occur in healthy subjects and rarely in patients with three-vessel disease (1 of 49 patients). In comparison to age-matched healthy subjects (v(max) = 1.46 +/- 0.52 mm/s), the patients with three-vessel disease showed a significant reduction in postischemic maximum erythrocyte velocity (v(max) = 0.85 +/- 0.55 mm/s), with a considerable shortening of the duration of reactive hyperemia. Patients with CAV demonstrated a total loss of postischemic reactive hyperemia (only 1 of the 11 patients presented a weak reactive hyperemia). Since no macroangiopathy was detectable in the upstream arm arteries, primary cutaneous microangiopathy can be assumed in patients with cardiac allograft vasculopathy and severe hypercholesterolemia.

This single-center, prospective, randomized, double-blind phase IV study with parallel-group design was performed to test whether injection of a newly designed non-ionic monomeric radiographic contrast medium in the axillary artery influences the ipsilateral cutaneous microcirculation. Twenty patients with coronary heart disease or suspected coronary heart disease were investigated. Ten patients received iobitridol and 10 normal saline solution. The confirmatory target variable was the capillary erythrocyte velocity (v(RBC)). The v(RBC) was continuously recorded before and up to 3 min after the injection of iobitridol or normal saline solution and subsequently evaluated off-line. Thirty seconds after injection of 20 ml iobitridol, v(RBC) was reduced by 32% (P < 0.05). This was the strongest reduction, but v(RBC) was reduced at all time points measured up to 180 s following the injection (P < 0.05 up to 180 s). The overall reduction in v(RBC) was also statistically significant (P 0.0446). In contrast, there was a tendency toward an increase in v(RBC) following injection of 20 ml normal saline (P 0.0512). There was also a tendency toward a difference in the time course of changes in v(RBC) following injection of iobitridol compared to normal saline (P 0.0607). The decrease in v(RBC) following iobitridol injection (standardized difference (SD) according to Cohen, 0.67) can be regarded as biometrically weak, and the increase following normal saline injection (SD, 0.24) as very weak. The microcirculatory disturbance induced by iobitridol injection is less severe than that due to comparable high-viscosity contrast media.

SummaryIt is known that angiodysplasia influence macrocirculation as well as microcirculation in patients with vWD. In the present study it was examined if intravital capillary microscopic dimensions (morphologic and dynamic) in skin (nailfold) in combination with rheologic parameters could give indications for the presence of vWD in patients with haemorrhagic diathesis.Patients with vWD (n = 100; 92 type 1: definite type 1:78 and possible type 1:14; 8 type 2A) have in comparison to patients with other haemorrhagic diathesis [thrombocytopathy (n = 122), thrombocytopenia (n = 101), severe haemophilia A (n = 50) and severe haemophilia B (n = 20), congenital dysfibrinogenaemia (n = 22), oral anticoagulation with phenprocoumone (n = 112)] and to apparently healthy subjects (n = 100) a significantly increased capillary torquation (median index: 3.5), a venolar and an arteriolar capillary dilatation (median: 16.5 µm; median: 15.1 µm) and the highest part of microscopic bleedings (extravasates) with 40% in the video capillary microscopy as morphological changes. Only the congenital dysfibrinogenaemia appears with a larger dilatation in venolar capillaries (median: 14.5 µm). Microscopic bleedings are much less common in other haemorrhagic diatheses with a frequency between 4% and 13%.In the vWD a significantly reduced duration of reactive hyperaemia (median: 150 sec). This is the only dynamic change that can be taken as a possible hint for a loss of flexibility within the precapillary vessels. A significantly reduced plasma viscosity (< 1.25 mPas) is typical for the vWD due to the increase of the shear stress in blood plasma because of the reduction of vWF-activities. Changes of the capillary morphology (dilatation, extravasates, capillary torquation) and the hypoplasmaviscosity are most sensitive for the vWD (75%, 65%, 40%, 80%) with a fairly high specifity (up to 93%) and a positive predictive value of 99%.As a conclusion it seems reasonable to discuss the introduction of video capillary microscopy as a screening test for haemostasiological and angiological centers.

Summary Background: In a controlled, randomized, prospective, open, comparative study we evaluated the platelet function of 112 p

The development of synthetic materials and textured polymers and their increasing use in medicine make research of biomaterials’ hemocompatibility very relevant. Problems arise from the polymorphism a

Background: Unwanted side-effects like thrombotic-thromboembolic processes accompany the intravascular use of catheters. The influence of the physico-chemical properties of the catheter materials on these processes is not completely understood. Methods: The haemocompatibility of angiography-catheters (n = 10) (Super Torque Plus®, CORDIS, Johnson&Johnson company) was examined in a perfusion-model filled with platelet-rich plasma and either compared to a non-thrombogenic (silicon-tube) or to a thrombogenic surface (glass). As test-parameters the number of single circulating thrombocytes, of circulating platelet-aggregates, of circulating activated thrombocytes (CD62) and the thrombin generation (thrombin antithrombin III-complexes) were evaluated. Results: None of the test-parameters showed differences between the non-thrombogenic control-system and the angiography-catheters. Both systems, however, differed significantly and relevantly from the system filled with the glass-beads (the thrombogenic control-systems). Conclusion: With respect to the platelet reactivity angiography-catheters of the examined type can therefore be regarded as non-thrombogenic or haemocompatible.

Chronic venous insufficiency (CVI) can cause ulcers of the lower limb having the character of a full thickness wound involving the subcutaneous tissues and fat. Healing requires wound contraction, connective tissue formation and finally reepithelialization. To induce wound healing, on an underlying disturbed environment due to longterm effects of CVI, artificial stimuli may be needed. In a placebo controlled study we tried topical application of autologous PDWHF (platelet derived wound healing factors), to achieve ulcer healing and improve the microangiopathy surrounding of the ulcer area, as there are decreased number of skin capillaries and reduction in cutaneous vascular reserve. Alterations of cutaneous circulation during the course of the study were documented by capillaroscopy, transcutaneous oxygen pressure and laser Doppler flux (LDF) measurements. We were able to recruit 15 patients a I suffering from chronic nonhealing venous stasis ulcers. Eleven of the 15 patients agreed to participate in a placebo-controlled double blind study, whereas 4 patients agreed to participate only if they would be treated with PDWHF. The median age and duration of ulceration of the 6 patients (3 male/3 female) treated with placebo were 71 years and 1089 days. The median age and duration of ulceration of the 9 patients (1 male/8 females) treated with PDWHF were 66 years and 732 days. Duration of therapy for the PDWHF group was 91 days, as compared to 154 days for the placebo group. Despite 2 completely healed ulcers, the expensive treatment did not reveal any significant clinical advantage. In den PDWHF group an ulcer area of 26.9 cm2 was measured at the beginning, of 26.2 cm2 at the end; in the placebo group, 34.7 cm2 and 35.5 cm2. The nonsignificant increase of the capillary density at the ulcer border in the active group as well as the increase in the tcPO2, in contrast to little change in both parameters in the placebo group, suggests neoangiogenic abilities to PDWHF, secondarily leading to a better blood distribution with higher oxygen tension.

Als Ursache unerwunschter Begleiterscheinungen nach Rontgenkontrastmitteln wurden unter anderem induzierte Mikrozirkulationsstorungen (infolge der Hyperviskositat/Hyperosmolalitat) diskutiert. In drei Vergleichsstudien wurde daher vor der Koronarangiographie gepruft, ob die Viskositat oder die Osmolalitat der Rontgenkontrastmittel bei Bolusinjektion die nachgeschaltete Mikrozirkulation beeinflust. Die Injektion von 20 ml eines Rontgenkontrastmittels mit einer Viskositat von 9,9 mPas und einer Osmolalitat von 770 mOsmol/kg H2O (Iopromid mit 370 mg Jod/ml) fuhrte zu einer signifikanten Abnahme der mittleren Erythrozytengeschwindigkeit in den nachgeschalteten Kapillaren um 51,3% (p=0,0001), wahrend Elektrolytlosung keinen Einflus hatte. Nach Injektion von 20 ml Iodixanol mit 270 mg Jod/ml (5,8 mPas, 290 mOsmol/kg H2O) kam es zu einer signifikanten Abnahme der kapillaren Erythrozytengeschwindigkeit um 60,8% (p=0,0001) bis zum Ende des Beobachtungszeitraumes, wahrend das niedrigviskose Iopentol mit 150 mg Jod/ml, aber vergleichbarer Osmolalitat (1,7 mPas, 340 mOsmol/kg H2O) keinen Einflus hatte (p=0,151). Nach der Injektion zweier hochviskoser, in der Osmolalitat aber unterschiedlicher Rontgenkontrastmittel nahm die kapillare Erythrozytengeschwindigkeit erheblich ab, der zeitliche Verlauf unterschied sich jedoch nicht (p=0,9890). Die Kapillarperfusion hangt damit signifikant von der Viskositat, nicht von der Osmolalitat des injizierten Rontgenkontrastmittels ab. Zur Vermeidung induzierter Mikrozirkulationsstorungen erscheint daher der Einsatz niedrigviskoser Kontrastmittel sinnvoll.

The problem of restenosis in blood vessels after balloon angioplasty could not be overcome by the use of metallic stents as had been anticipated. With respect to restenosis, clinical and experimental results now focus the attention on the risk that stents could initiate or potentiate vascular lesions, especially by inhomogenous stent expansion. Here the stent design seems to dominante depending on the use of well rounded structural stent-elements with appropriate surfaces and a material deposition which is compatible with a homogeneous stent expansion. With respect to hemocompatibility the surface quality of the stents is of great importance, too. Coating of surfaces of metallic stents for the enhancement of hemocompatibility might create new risks of blood vessel damages and requires a careful consideration of the co-expansional behaviour of the metallic substrate and the coating material. With these problems in mind the surface coated stent Tensum 3 of the Biotronik company was investigated.

In vitro cultured autologous chondrocytes can be used for implantation to support cartilage repair. For this purpose, a very small number of autologous cells harvested from a biopsy have to be expanded in monolayer culture. Commercially available polymer surfaces lead to chondrocyte dedifferentiation. Hence, the demanding need for optimized polymers and surface topologies supporting chondrocytes' differentiated phenotypes in vitro arises. In this study we explored the effect of tailored cell culture plate inserts prepared from polystyrene (PS) and polyether imide (PEI) exhibiting three different roughness levels (R0, RI, RII) on chondrocyte morphology, metabolism and gene expression profile. As a control, commercially available tissue culture plastic (TCP) dishes were included. Primary porcine articular chondrocytes were seeded on tailored PS and PEI inserts with three different roughness levels. The metabolic activity of the chondrocytes was determined after 24 hours using alamar blue assay. Chondrocyte gene expression profiles (aggrecan, type I and type II collagen) were monitored after 48 hours using Real Time Detection (RTD)-PCR. Chondrocytes cultured on PS and PEI surfaces formed cell clusters after 24 and 48 hours, which was not observed on TCP. The metabolic activity of chondrocytes cultured on PS was lower than of chondrocytes cultured on PEI, but also lower than on TCP. Gene expression analyses revealed an elevated expression of cartilage-specific aggrecan and an impaired expression of both collagen types by chondrocytes on PS and PEI compared with TCP. In summary, PEI is a biocompatible biomaterial suitable for chondrocyte culturing, which can be further chemically functionalized for generating specific surface interactions or covalent binding of biomolecules.

The membrane of red blood cells consists of a phospholipid bilayer with embedded membrane proteins and is associated on the cytoplasmatic side with a network of proteins, the membrane skeleton. Band3 has an important role as centre of the functional complexes e.g. gas exchange complex and as element of attachment for the membrane skeleton maintaining membrane stability and flexibility. Up to now it is unclear if band3 is involved in the morphology change of red blood cells after contact with radiographic contrast media. The study revealed for the first time that Iopromide induced markedly more severe alterations of the membrane skeleton compared to Iodixanol whose effects were similar to erythrocytes suspended in autologous plasma. A remarkable clustering of band3 was found associated with an accumulation of band3 in spicules and also a sequestration of band3 to the extracellular space. This was evidently accompanied by a gross reduction of functional band3 complexes combined with a dissociation of spectrin from band3 leading to a loss of homogeneity of the spectrin network. It could be demonstrated for the first time that RCM not only induced echinocyte formation but also exocytosis of particles at least coated with band3.

The chain length and end groups of linear PEG grafted on smooth surfaces is known to influence protein adsorption and thrombocyte adhesion. Here, it is explored whether established structure function relationships can be transferred to application relevant, rough surfaces. Functionalization of poly(ether imide) (PEI) membranes by grafting with monoamino PEG of different chain lengths (Mn =1 kDa or 10 kDa) and end groups (methoxy or hydroxyl) is proven by spectroscopy, changes of surface hydrophilicity, and surface shielding effects. The surface functionalization does lead to reduction of adsorption of BSA, but not of fibrinogen. The thrombocyte adhesion is increased compared to untreated PEI surfaces. Conclusively, rough instead of smooth polymer or gold surfaces should be investigated as relevant models.

Interactions of cells with polymer-based biomaterials are influenced by properties of the substrate. Polymers, which are able to induce cell specific effects, gain increasing importance for biotechnology and regenerative therapies. A test system was developed, which allows studying primary human keratinocytes and fibroblasts in mono- and cocultures to analyze and operate the effect of polymer properties. This system offers to identify polymers for keratinocyte cultivation or wound dressings, since adherence, viability and functionality can be analyzed. Especially the coculture system enables the characterization of potential cell specific effects of polymer-based biomaterials. To establish a coculture test system, it is challenging to find a suitable culture medium, to identify initial seeding densities for comparable cell growth and to develop methods to distinguish and characterize both cell types. Poly( n -butyl acrylate) networks (cP n BAs) as model biomaterials were used to demonstrate the applicability of our newly developed coculture screening system for differential cell growth. The apparent Young's modulus of the cP n BAs differentially regulated fibroblasts and keratinocytes. Particularly, cP n BA73 with an apparent Young's modulus of 930 ± 140 kPa measured in phosphate buffered saline (PBS) solution at ambient temperature seemed to have favoring properties for keratinocyte adhesion, while fibroblast adhesion was not affected. For keratinocytes the concentration of some pro-inflammatory cytokines was lower on cP n BA73 and a decreased deposition of collagen, elastin and fibronectin was observed in the coculture.

Gelatins functionalized with desaminotyrosine (DAT) or desaminotyrosyl tyrosine (DATT) form physically crosslinked hydrogels, due to the interactions between the introduced aromatic moieties and gelatin triple helices, whose extent depends on the thermal treatment of the material. The G-modulus of these hydrogels can be tailored to the range of the natural extracellular matrix by adjusting the degree of crosslinking. While these gelatin-based materials have been shown to be not angiogenic, the aim of the study was to evaluate whether these biomaterials influence the regulation of blood vessels when positioned on the chorionallantoic membrane (CAM) of fertilized eggs. The results clearly indicate that the DAT-functionalized gelatin led to an increase of the diameter of the blood vessels in the CAM, which at the same time is probably associated with an increased blood flow in these CAM vessels. The vessel diameters of the four groups (DAT-functionalized gelatin, DATT-functionalized gelatin, plain gelatin, control group without gelatin, each n = 10) differed significantly (p0.0001). Vessels in the CAM exposed to the DAT-functionalized gelatin showed with 36.4 μm ± 3.4 μm the largest mean diameters compared to the mean diameters of the samples exposed to DATT gelatin (16.0 μm ± 0.8 μm; p0.05) and the plain gelatin (21.2 μm ± 1.0 μm; p0.05), which both did not differ significantly from the vessels of the control group. The biocompatibility of the materials in vitro motivates the exploration of their application as matrix in local drug-release systems with short half-life times (one hour up to several days).

Red blood cells demonstrate a unique ability for repeated large deformation. Under the influence of a variety of agents, shapes other than the discocyte - e.g. stomatocytes or echinocytes - can be observed. Some radiographic agents induce shape changes from discocytic to echinocytic cells. Especially the echinocyte formation is associated with a rigidification of the cells bearing the risk of a hindered capillary passage of the echinocytes. The mechanisms leading to the formation of echinocytes are not well understood assuming that the membrane cytoskeleton is a key player. That is why this examination was focused on the participation of components of the membrane cytoskeleton in the formation of echinocytes and the protrusions accompanying the formation of echinocytes. Two radiographic contrast media approved for intra-arterial application were used to study echinocyte formation (Iodix- anol320; Iopromide370). In the in vitro study serious changes in the membrane cytoskeleton were only found in those erythrocytes incubated in plasma supplemented with Iopromide370 (30%v/v). The shape of the spectrin net was completely altered; from the more homogeneous distribution - typical of cells in autologous plasma and also of cells in plasma supplemented with Iodixanol320 - to a distribution of spectrin concentrated in the membrane-near regions with the appearance of spectrin-actin co-localization. Co-localized spectrin with actin was also found around the membranous roots of protrusions which resemble exocytotic processes. In central parts of the cells there was a pronounced dissociation of spectrin and actin; green coloured condensed spectrin bundles originating from the cell membrane reached up to the root of the protrusions. Separate from this there were also fine long actin fibres passing through the whole cell. The incubation of erythrocytes in plasma supplemented with Iopromide370 induced rounded bubble-like protrusions from the cell membrane containing almost completely long bundles of actin fibres. The examination confirmed earlier studies showing that some radiographic contrast media are able to induce echinocyte formation. Furthermore, subcellular mechanisms were revealed explaining the different effects of Iodixanol in comparison to Iopromide.