Differences in human and sheep platelet adherence, aggregation and activation induced by glass beads in a modified chandler loop-system.

In human cardiovascular research, sheep in particular are used as a large animal model in addition to pigs. In these animals, medical products, developed and tested for human medical purposes, are almost exclusively used in interventional studies. Therefore, the extent to which platelets from human and ovine blood differ in terms of adherence, aggregation and activation after a 4- or 8-minutes exposure to glass was investigated. Testing was performed with platelet-rich plasma (PRP) and a modified chandler loop-system, with 4- and 8-minute blood-material exposure times corresponding to 20 and 40 test cycles, respectively, through the entire silicone tube loop of the test system.In sheep and human PRP, contact with the silicone tubing resulted in a decrease in platelet count after 4 minutes and 20 test cycles, respectively. Four more minutes (20 additional test cycles) caused a further decrease of the platelet count only in sheep PRP. When the silicon tube was partly filled with glass beads, these effects were more pronounced and stronger in sheep then in human PRP.The mean platelet volume, which was used as parameter for platelet aggregation, did not change over time in human PRP without glass exposure. With glass exposure in human and sheep PRP the mean platelet volume increased within 40 test cycles, but this increase was stronger in sheep than in human PRP.Regarding activation behavior, the activation markers CD62P and CD63 were detectable only in < 30% (sheep) and < 45% (human) of platelets, whereas after 8 min of glass exposure, the proportion of CD62P+ and CD63+ cells was more increased than before only in sheep. These results indicate that ovine platelets adhere more strongly to glass and show stronger aggregation behavior after glass contact than human platelets, but that ovine and human platelets differ only slightly in activability by glass.

Differences in human and minipig platelet number, volume and activation induced by borosilicate glass beads in a modified chandler loop-system.

The pig is the most widely used large animal model in Europe, with cardiovascular research being one of the main areas of application. Adequate refinement of interventional studies in this field, meeting the requirements of Russel and Burchs' 3 R concept, can only be performed if blood-contacting medical devices are hemocompatible. Because most medical devices for cardiovascular interventional procedures are developed for humans they are tested mostly for compatibility with human blood. The aim of this study was therefore to determine whether there are differences in behavior of porcine and human platelets when they come into contact with glass, which was used as an exemplary thrombogenic material. For this purpose changes of platelet count, platelet volume and platelet expression of the activation markers CD61, CD62P and CD63 were measured using a modified chandler loop-system simulating the fluidic effects of the blood flow. Minipig and human platelets showed significant differences in number and volume, but not in activation after 4-8 min exposure to glass.

Cutaneous microcirculation in patients with peripheral arterial occlusive disease: Comparison of capillary blood circulation in the nail fold of finger and toe.

In patients with peripheral arterial occlusive disease (PAOD) a restricted circulation in cutaneous microvessels has been reported. In this study the velocity of erythrocytes (very) in finger nailfold capillaries - a vascular area without upstream macroangiopathy - and also in toe nailfold capillaries - a post-stenotic area -was investigated using capillary microscopy in apparently healthy subjects and patients with PAOD. Already in finger nailfold capillaries very of patients with PAOD under resting conditions was significantly lower than in capillaries of healthy subjects. This was also true for the circulation in toe capillaries. In addition, the erythrocyte velocities under resting conditions in the toe capillaries were significantly lower than in the finger capillaries. Similar results were found for the duration and the maximum velocity of postocclusive hyperemia. It is concluded that the resting blood flow in the skin microcirculation is impaired in PAOD patients, both under resting conditions and during postocclusive hyperemia in finger as well in toe nailfold capillaries.

Pododermal angioarchitecture in the equine hoof wall: A light and scanning electron microscopic study of the wall proper.

BACKGROUND: Blood supply is an important factor for the normal function of the equine hoof, but earlier studies present conflicting data on functional characteristics of its angioarchitecture. OBJECTIVE: Emphasis was laid on demonstration of the microvascularisation in the different hoof wall regions, aiming at assessment of specialised vascular structures, e.g. vascular sphincter mechanisms and arteriovenous anastomoses. METHODS: The angioarchitecture of the adult pododerma in the equine hoof wall was examined by scanning electron microscopy of micro-corrosion casts assisted by exemplary histological and immuno-histochemical characterisation of the pododermal vasculature. RESULTS: The microvasculature of the lamellae and terminal papillae in all hoof wall regions was described in detail. Focal dilations and microvascular sphincters were a common feature. In contrast to former investigations, true arteriovenous anastomoses were detected at the base of the primary lamellae and the terminal papillae only, while thoroughfare channels proved a regular element within the microvasculature of the wall proper. Bicuspid venous valves were detected as regular feature. For the first time, the alpha-smooth muscle actin-reactivity of the microvascularisation in the hoof wall was systematically assessed, verifying its specialised vasomotor devices. CONCLUSIONS: The vasculature of the hoof wall displays specific angio-adaptations to high pressure and tensile load.

Growth-related micromorphological characteristics of the porcine femoral artery.

BACKGROUND: In cardiovascular research small pigs breeds like Göttingen® minipigs (GM) are established animal models, but systematic data about the micromorphology of the GM vasculature at different ages are scarce. OBJECTIVE: The study was aimed at gaining knowledge about the micromorphology of the femoral artery (FA) from German Landrace pigs (DL) and GM during the period of growth over a body weight range of 10-40 kg. METHODS: FA samples from DL aged two or three months were compared to GM ones, aged 18 or 40 months using transmitted light microscopy. RESULTS: All FA samples showed typical characteristics of muscular arteries. Growth was associated with increased vessel wall thickness. In the GM this resulted in a slight decrease of the luminal diameter (LD), while in the DL pigs, an increase of the LD and smooth muscle cell content (10%) with decreased elastic fiber content (10%) has been detected. In contrast, within the 22 months lasting growth period of the GM, the tunica media content of smooth muscle cells and elastic fibers remained stable. CONCLUSIONS: FA maturation strongly depends on the pig breed and age. It can be different from what is described in humans.

Antiviral activity of an aqueous extract derived from Aloe arborescens Mill. against a broad panel of viruses causing infections of the upper respiratory tract.

BACKGROUND: A number of antiviral therapies have evolved that may be effectively administered to treat respiratory viral diseases. But these therapies are very often of limited efficacy or have severe side effects. Therefore there is great interest in developing new efficacious and safe antiviral compounds e.g. based on the identification of compounds of herbal origin. HYPOTHESIS: Since an aqueous extract of Aloe arborescens Mill. shows antiviral activity against viruses causing infections of the upper respiratory tract in vitro we hypothesised that a product containing it such as Biaron C(®) could have an antiviral activity too. STUDY DESIGN: Antiviral activity of Bioaron C(®), an herbal medicinal product consisting of an aqueous extract of Aloe arborescens Mill., Vitamin C, and Aronia melanocarpa Elliot. succus, added as an excipient, was tested in vitro against a broad panel of viruses involved in upper respiratory tract infections. METHODS: These studies included human adenovirus and several RNA viruses and were performed either with plaque reduction assays or with tests for the detection of a virus-caused cytopathic effect. RESULTS: Our studies demonstrated an impressive activity of Bioaron C(®) against members of the orthomyxoviridae - influenza A and influenza B viruses. Replication of both analysed influenza A virus strains - H1N1 and H3N2 - as well as replication of two analysed influenza B viruses - strains Yamagatal and Beiying - was significantly reduced after addition of Bioaron C(®) to the infected cell cultures. In contrast antiviral activity of Bioaron C(®) against other RNA viruses showed a heterogeneous pattern. Bioaron C(®) inhibited the replication of human rhinovirus and coxsackievirus, both viruses belonging to the family of picornaviridae and both representing non-enveloped RNA viruses. In vitro infections with respiratory syncytial virus and parainfluenza virus, both belonging to the paramyxoviridae, were only poorly blocked by the test substance. No antiviral activity of Bioaron C(®) was detected against adenovirus - a non-enveloped DNA virus. CONCLUSIONS: These results represent the first proof of a selective antiviral activity of Bioaron C(®) against influenza viruses and create basis for further analyses of type and molecular mechanisms of the antiviral activity of this herbal medicine.

[Hyperthyroidism, eosinophilia, and fever in a 64-year-old patient]. / Hyperthyreose, Eosinophilie und Fieber bei einem 64-jährigen Patienten.

We report on a male patient suffering from loss of weight, fatigue, fever, eosinophilia, and hyperthyreoidism. The echocardiogram revealed a left atrial mass originating from the posterior mitral leaflet. In combination with the constitutional symptoms a left atrial myxoma was diagnosed. The tumor was surgically removed. Postoperatively therapy with corticosteroids and thiamazole was stopped. During follow-up, eosinophilia and hyperthyreodism could no longer be detected.

Ross procedure.

INTRODUCTION: In 1967 Donald Ross introduced the subcoronary Ross procedure consisting of transplantation of the autologous pulmonary valve into aortic position. We describe our 15-year experience in Ross procedures. METHODS: 576 subcoronary operations have been performed (436 male and 140 female patients); the mean age was 45±11.9 years. (range, 13 to 70 years). The mean follow-up was 7±4.2 years (range, 0 to 16 years). There were 4597 patient years at follow-up with a clinical completeness of 95% and echo completeness of 91%. RESULTS: There were two operative deaths (0.3%) and 31 patients with reoperation. The survival is similar to that of the normal population and the freedom from allo- and autograft reoperation is 87% at 15 years. Autograft regurgitation at last examination was grade 0 in 40%, trace in 54%, grade I in 19%, grade II in 4% and grade III in 0.4%; the pressure gradient was smaller than 5 mmHg in 57% and between 5 and 10 mmHg in 24%. Only 6% had a transvalvular pressure gradient of more than 10 mmHg. DISCUSSION: After 15 years of experience it can be concluded that the subcoronary technique provides near normal survival in adult patients, with excellent hemodynamics and acceptable rate of reoperations.

[Surgical atrial fibrillation ablation therapy and postoperative monitoring]. / Rhythmuschirurgie des Vorhofflimmerns und postoperatives Monitoring.

Atrial fibrillation represents the most common atrial arrhythmia seen in clinical practice. The surgical treatment of atrial fibrillation is recommended in symptomatic patients as well as in asymptomatic patients at low postoperative risk. As a "stand alone" procedure, surgical ablation therapy is indicated after failed catheter ablation therapy, which occurs increasingly due to the high number of catheter-based ablation techniques. In order to gain acceptance among patients as well as referring cardiologists, the surgical ablation procedure ought to be performed in a minimally invasive fashion and with a very high success rate. When applied in an interdisciplinary approach by cardiologists/electrophysiologists and cardiothoracic surgeons, both ablative techniques have the potential to treat atrial fibrillation effectively and in the long-term. In order to document the true heart rhythm after ablation therapy, intermittent "snapshot" ECG documentation ought to be avoided. Small leadless devices that can be implanted subcutaneously enable full heart rhythm disclosure with documentation of atrial arrhythmias. The modern technique of implantable loop recorders permits individualized treatment for each patient.

[Diagnostic pathways and pitfalls in acute thoracic aortic dissection: practical recommendations and an awareness campaign]. / Diagnostische Wege und Irrwege der akuten thorakalen Aortendissektion: Praktische Empfehlungen und Aufklärungskampagne.

Despite significant improvements in the surgical therapy of acute aortic dissection (AAD), mortality rates in the initial phase remain unacceptably high. Early diagnosis and therapy are essential to improving prognosis in these patients. A prerequisite of prompt and correct diagnosis is"thinking of it". Delayed or incorrect diagnosis can often have catastrophic results.The reported acute chest and back pain of a tearing, stabbing nature combined with the physiognomy of Marfan syndrome often arouse the clinical suspicion of AAD, prompting immediate imaging of the thoracic aorta and therapy. For less clear cases, additional hints drawn from the patient history and special findings from the medical examination are presented schematically in a diagnostic pathway. As an innovative form of diagnosis, preventive echocardiographic screening in high risk groups is discussed.To heighten awareness of AAD and the importance of its correct diagnosis, the poster campaign "Thinking of it can save lives" has been initiated. The poster depicts AAD schematically, indicates Marfan syndrome as a risk factor for AAD in young people and illustrates a CT scan as the most frequently performed imaging technique with high sensitivity and specificity.

Inhibition of caspase-3 differentially affects vascular smooth muscle cell apoptosis in the concave versus convex aortic sites in ascending aneurysms with a bicuspid aortic valve.

Apoptosis of vascular smooth muscle cells (VSMCs) is involved in bicuspid aortic valve (BAV) ascending aorta aneurysms characteristically affecting the convex site. Caspase-3 is a pivotal effector of the apoptosis machinery. The aim of this study was to investigate the impact of an inhibited caspase-3 pathway on apoptosis in convex and concave sites VSMCs of ascending aortic tissue in vitro. Specimens from the convex and concave sites of ascending aortic aneurysm were collected from nine patients with BAV (mean age 58.7+/-14.8). Cultured VSMCs were characterized morphologically and immunohistochemically. Apoptosis activity was measured in VSMCs using Annexin V-APC with propidium iodide nuclear staining in flow cytometry. To investigate apoptotic modulation, caspase-3 was inhibited by N-acetyl-Asp-Glu-Val-Asp-CHO (Ac-DEVD-CHO). Apoptosis was initiated by calcium chloride. Inhibition of caspase-3 with Ac-DEVD-CHO protected VSMCs against calcium chloride apoptosis significantly more in the concave site than in the convex site (25.8+/-9.8 versus 38.5+/-8.0% apoptotic cells, p=0.01). Morphological scanning using light microscopy revealed typical VSMCs. We provide evidence that VSMCs show a different behavior with respect to apoptosis in the concave versus the convex sites in BAV ascending aortic aneurysm. Inhibition of caspase-3 resulted in a significantly increased protection of VSMCs against apoptosis in the concave site compared with the convex site in ascending aortic aneurysm in BAV. These findings may have some implications on understanding aneurysmal formation and its potential modulation.

Transmyocardial laser revascularization combined with intramyocardial endothelial progenitor cell transplantation in patients with intractable ischemic heart disease ineligible for conventional revascularization: preliminary results in a highly selected small patient cohort.

OBJECTIVE: Transmyocardial laser revascularization for angina relief and intramyocardial autologous endothelial progenitor cell injection for neoangiogenesis may offer a new treatment strategy for patients with intractable ischemic heart disease. METHODS: Transmyocardial laser revascularization and intramyocardial injection of bone marrow-derived CD133+ cells was performed in six highly symptomatic patients. Transmyocardial laser channels were created and isolated CD133+ cells were injected intramyocardially. All patients were followed up for a minimum of 6 months postoperatively. RESULTS: One patient died shortly after the operation due to refractory heart failure. In the five survivors, CCS class improved as well as left ventricular ejection fraction. Left ventricular end-diastolic volume and myocardial perfusion varied between the patients. All patients described a considerable improvement in quality of life postoperatively. Repeated 24-hour Holter monitoring revealed no significant arrhythmias. CONCLUSIONS: In this small patient cohort, intramyocardial CD 133+ cell injection combined with transmyocardial laser revascularization led to an improvement in clinical symptomatology in all patients and in left ventricular function in 4 out of 5 patients, with an unclear effect on myocardial perfusion. Caution is advised when employing this therapy in patients with severely depressed left ventricular function.

Impact of graft size and commissural resuspension height on aortic valve competence in valve-sparing aortic replacement under physiological pressures.

BACKGROUND: Valve competence in valve-sparing aortic root replacement has been described as being influenced by commissural height as well as graft size. The aim of this study was to investigate the impact of a gradual reduction of commissural height and graft diameter on aortic insufficiency under physiological conditions in an IN VITRO model. METHODS: Porcine aortic valves were reimplanted into a tubular graft and a native commissural height was obtained. Subsequently the height was reduced by 10 % and 20 %, respectively. To investigate the impact of graft size, a 30 % reduction of the prosthesis diameter was carried out in valves with both native and reduced commissural heights. All conditions were investigated under pulsatile flow simulation and static pressure exposure. RESULTS: Reduction of commissural height caused regurgitation at both 10 % and 20 % lower heights, which was more pronounced in grafts with 20 % reduction. Graft undersizing resulted in significant reflux, with regurgitation even occurring with valves in a native commissural position. CONCLUSIONS: Valve competence is impaired both by the reduction of commissural height and by reduced graft size. In particular, reimplantation of aortic valves into undersized grafts promotes valve insufficiency even if commissural height is well adjusted.

Rate of paraplegia and mortality in elective descending and thoracoabdominal aortic repair in the modern surgical era.

BACKGROUND: The risk of paraplegia and hospital death is the major concern in the surgical repair of descending and thoracoabdominal aortic pathologies. For specific indications, the evolving technology of endovascular stent grafting is becoming increasingly popular. We reviewed our results for elective surgical repair of various aortic pathologies with respect to this innovative therapeutic background. METHODS: From July 1993 to April 2006, 56 patients (mean age 55+/-16 years, range 25 to 80 years, 62.5% males) underwent elective surgical repair of the descending (n=37, 66.1%) and thoracoabdominal aorta (n=19, 33.9%), including seven reoperations and five cases of previous endovascular stent grafting. The underlying pathologies were: degenerative aneurysm (n=21), type B aortic dissection (n=24), and Marfan's syndrome with a chronic type B dissection and an increase in the diameter of the descending aorta (n=11), respectively. Most patients were operated using deep hypothermic circulatory arrest. RESULTS: Thirty-day mortality was 5.4 % (n=3). Two patients died of myocardial infarction, one after coronary stent occlusion. Another patient died due to ventricular disruption at the side of the left ventricular apical vent. The rate of paraplegia was 3.6% (n=2) with one case of complete and one of incomplete paraplegia. Survival at five years was 78%. CONCLUSIONS: If modern surgical principles are used in elective descending and thoracoabdominal aortic repair, surgery can be performed with a low postoperative risk for hospital death or paraplegia. These results should be taken into account when evaluating alternative therapeutic strategies in patients with similar pathologies.

[Confusion Assessment Method for the Intensive Care Unit (CAM-ICU): diagnosis of postoperative delirium in cardiac surgery]. / Confusion Assessment Method for the Intensive Care Unit (CAM-ICU): diagnostik des postoperativen delirs bei kardiochirurgischen Patienten.

OBJECTIVE: Since 2001 the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), a method for the diagnosis of delirium, has been available for the Anglo American area which can also be applied to mechanically ventilated patients. This study was conducted to answer the following questions: 1. Can a German version of the CAM-ICU be applied to patients after cardiac surgery? 2. What is the prevalence rate of postoperative delirium after cardiac surgery diagnosed by the CAM-ICU? 3. Do patients with and without the diagnosis delirium differ in the clinical variables usually associated with this disorder in cardiac surgery? METHODS: A total of 194 patients undergoing cardiac surgery served as the analysis sample (85.5% of the total group). The CAM-ICU was carried out every day for 5 days after the operation. Sociodemographic and clinical variables were collected to examine the validity of CAM-ICU. Postoperative complaints were assessed by the Anaesthesiological Questionnaire for Patients (ANP). RESULTS: Postoperatively, the CAM-ICU could be applied to almost all patients without any problems. The prevalence rate of delirium was 28.4% and 85.5% of the delirium diagnosed was a hypoactive subtype when diagnosed for the first time. Patients with delirium diagnosed by CAM-ICU were older (p<0.001), had a lower educational level (p<0.05), longer anaesthesia time and operation time (p<0.05), a longer postoperative ICU stay (p<0.001), were mechanically ventilated for a longer time postoperatively (p<0.001), more often reintubated (p<0.01) and had higher leucocytes postoperatively (p<0.10). More patients with delirium had the lowest postoperatively measured oxygen saturation below 95% (p<0.01). CONCLUSION: The CAM-ICU is an economic method for the assessment of delirium which can easily be learned. It can be applied to patients after cardiac surgery without any problems.

Preexisting atrial fibrillation as predictor for late-time mortality in patients with end-stage renal disease undergoing cardiac surgery--a multicenter study.

BACKGROUND: Although patients with end-stage renal disease (ESRD) are considered to be high-risk patients in cardiac surgery, the reported studies are rather small, resulting in unsatisfactory analyses of outcome determinants. Therefore, we aimed to identify possible risk factors, with a particular focus on the impact of pre-existing atrial fibrillation (AF) on the postoperative short-term and long-term mortality of ESRD patients undergoing cardiac surgery. METHODS: In a multicenter study 522 patients with ESRD undergoing CABG only (62.9 %), valve surgery only (17.2 %), or both (19.9 %) with comparable demographic and other cardiac risk factor characteristics were investigated retrospectively over a period of 10 years. The outcome was divided into perioperative (within 30 days) and late morbidity and mortality, and multivariate analysis was performed for both. RESULTS: The mean perioperative mortality was 11.5 % and the 5-year survival rate was 42 %. Emergency surgery, insulin-dependent diabetes mellitus, the number of vein grafts and age were identified as risk factors whereas complete revascularization, the use of an internal thoracic artery and the presence of sinus rhythm were identified as beneficial factors for long-term survival. 14.1 % of all patients had pre-existing AF. Although AF was not identified as an independent risk factor for perioperative mortality ( P = 0.59), it was identified as an independent predictor for late mortality ( P < 0.001). Median survival of patients without AF was 1816 days, while for patients with AF it was only 715 days. CONCLUSIONS: AF does represent an independent predictor for long-term but not perioperative mortality in patients with ESRD. However, effective treatment of AF is controversially discussed. Anticoagulation therapy or perioperative ablation of the arrhythmia should be considered in order to improve the survival of these patients.

Types of reconstructive surgery of the aortic valve.

The aortic valve is part of the aortic root which is wedged between the heart and the ascending aorta, maintaining a directional flow throughout life-span. Beside different types of aortic valve replacements, reconstructive techniques are increasingly performed to restore normal aortic valve function. To apply these operations, understanding of normal and pathological valve anatomy and physiology is of basic importance. In addition, a widely accepted uniform aortic valve and root terminology is desirable for a proper scientific communication. Reconstructive techniques themselves can be divided into isolated reconstruction of aortic valve/root structures and the isolated replacement of one or more structures. Examples for the former ones are commissurotomy, cusps plication, decalcification or extension as well as plications of other aortic root structures (i.e. the intercusp triangles or the basal annulus). Examples for the latter ones are the remodeling and reimplantation techniques and their modifications. Replacement of the ascending aorta at the sinotubular level for the adjustment of the commissures to restore aortic root geometry also belongs to this group of techniques for aortic valve reconstruction. In this review article a systematic description of the current reconstructive techniques to restore adequate aortic valve function as well as clinical data are presented.