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The heart and brain are constantly interacting under normal physiological conditions. This interaction is under the control of the autonomic nervous system with parasympathetic and sympathetic nerve fibers including the participating brain structures. Pathological conditions, such as epilepsy and ischemic cerebral stroke influence heart function, especially the frequency and may result in severe arrhythmia. An asymmetric influence of the left and right brain hemispheres on the heart rate is still under debate. Conversely, the influence of the heart in cases of acute cardiac arrest on brain function is equally relevant and a common clinical problem after resuscitation. We review the damaging cascade of global cerebral hypoxia and the value of different diagnostic procedures as well as the ethical problem of the point in time of termination of consciousness and the instruments for estimating the prognosis.

In recent years a considerable number of translational research studies on intracerebral hemorrhage and ischemic stroke have been published, which are characterized by a particular proximity to practical clinical questions. Animal research has provided insights into the pathophysiological processes and therapy effects, which have so far only been insufficiently investigated in clinical studies. This includes the effectiveness of a rapid reversal of anticoagulation in cases of anticoagulation-associated intracerebral hemorrhage and the safety of thrombolytic treatment in ischemic stroke occurring during treatment with anticoagulants. With the approval of the direct oral anticoagulants these problems have become of particular contemporary relevance. Of course, results from experimental translational studies on stroke cannot be directly translated into clinical routine. Nevertheless, these investigations help to understand the underlying processes and mechanisms and provide proof of concept data for new treatment strategies. This review summarizes the most relevant results in this field of research with a particular focus on practical clinical questions.

Posttraumatic stress disorder (PTSD) was previously thought to be a psychological reaction precipitated by exposure to war, sexual and physical violence; however, PTSD is also prevalent after life-threatening medical events, such as stroke and myocardial infarction. After such events PTSD is often underdiagnosed despite the fact that it is clearly associated with adverse clinical outcomes including recurrence of cardiac events and increased mortality. Moreover, PTSD increases the risk of vascular events. This review summarizes the bidirectional relationship between PTSD and vascular diseases and outlines current knowledge regarding clinical features, prevalence and the putative underlying pathophysiological mechanisms.

The estimation of potassium in the serum is basis for the diagnosis of potassium disturbances. The value is a result of intake, excretion and internal distribution of potassium between intra- and extracellular compartments of the body. Clinically, we often see disturbances of potassium. The causes are explained by an aging population with morbidities that warrant diuretic treatment on the one side, and chronic kidney diseases on the other. In the first cases, we see hypokalaemia, in the latter hyperkalaemia. Both can lead to increased mortalities which are often labelled as "sudden heart death" without finding the underlying mechanism to be potassium driven. This is due to the fact that cardiac arrhythmias (ventricular fibrillation, heart block) lead to cardiac arrest. The pathophysiological understanding of the principles is the key for the guidance of diagnosis and therapy of the disturbances of potassium metabolism. Only by that, a decrease in mortality can be accomplished.

Disturbances in magnesium homeostasis are frequent clinical conditions, particularly the prevalence of hypomagnesaemia is high. However, it remains an open question which laboratory method is optimal to assess the magnesium level in the body. Most frequently physicians measure total magnesium in serum. Many associative data from observational studies point towards an association between low magnesium levels and increased cardiovascular risk as well as increased mortality. Vice versa, normal-to-high magnesium levels in patients with advanced renal failure translate to a better outcome. The present review summarizes our knowledge on protective effects of magnesium. Additionally, we address the limited evidence supporting targeted magnesium supplementation.

Lowering plasma low-density lipoprotein cholesterol (LDL-C) levels to individual therapeutic goals is one of the most effective measures for the prevention of cardiovascular disease. Besides dietary measures, this can be achieved pharmaceutically by inhibition of hepatic cholesterol synthesis with statins or inhibition of intestinal cholesterol absorption (e.g., ezetimibe and bile acid sequestrants). Decisive for lowering LDL is an increased hepatic uptake of circulating LDL via an increase in LDL receptors (LDLR) in hepatic cell membranes. The formation of new LDLR and recirculation of existing LDLR play a decisive role in this process. An important modulator of LDLR is proprotein convertase subtilisin/kexin type 9 (PCSK9). In the last years genetic studies have identified several mutations in the PCSK9 gene leading to a gain of function and carriers of these mutations suffer from autosomal dominant hypercholesterolemia. In contrast, carriers of PCSK9 loss of function mutations show very low plasma LDL-C concentrations and a markedly reduced risk for coronary artery disease. These fundamental discoveries have sparked the development of a completely novel therapeutic approach to treating hypercholesterolemia. At present, inhibition of PCSK9 by monoclonal antibodies presents the most promising therapeutic approach. First human antibodies were recently approved as the first immunotherapeutic agents for the treatment of severe hypercholesterolemia and in patients with statin intolerance. An additional PCSK9 antibody is presently being studied in phase III clinical trials.

Over the last decade endovascular stenting of aortic aneurysm (EVAR) has been developed from single centre experiences to a standard procedure. With increasing clinical expertise and medical technology advances treatment of even complex aneurysms are feasible by endovascular methods. One integral part for the success of this minimally invasive procedure is innovative and improved vascular imaging to generate exact measurements and correct placement of stent prosthesis. One of the greatest difficulty in learning and performing this endovascular therapy is the fact that the three-dimensional vascular tree has to be overlaid with the two-dimensional angiographic scene by the vascular surgeon.We report the development of real-time navigation software, which allows a three-dimensional endoluminal view of the vascular system during an EVAR procedure in patients with infrarenal aortic aneurysm. We used the preoperative planning CT angiography for three-dimensional reconstruction of aortic anatomy by volume-rendered segmentation. At the beginning of the intervention the relevant landmarks are matched in real-time with the two-dimensional angiographic scene. During the intervention the software continously registers the position of the guide-wire or the stent. An additional 3D-screen shows the generated endoluminal view during the whole intervention in real-time.We examined the combination of hardware and software components including complex image registration and fibre optic sensor technology (fibre-bragg navigation) with integration in stent graft introducer sheaths using patient-specific vascular phantoms in an experimental setting. From a technical point of view the feasibility of fibre-Bragg navigation has been proven in our experimental setting with patient-based vascular models. Three-dimensional preoperative planning including registration and simulation of virtual angioscopy in real time are realised.The aim of the Nav-CARS-EVAR concept is reduction of contrast medium and radiation dose by a three-dimensional navigation during the EVAR procedure. To implement fibre-Bragg navigation further experimental studies are necessary to verify accuracy before clinical application.

Atherosclerosis causes clinical symptoms through luminal narrowing by stenosis or by precipitating thrombi that obstruct blood flow to the myocardium (coronary artery disease), central nervous system (ischemic stroke) or lower extremities (peripheral vascular disease). The most common of these manifestations of atherosclerosis is coronary artery disease, clinically presenting as either stable angina or acute coronary syndromes. Atherosclerosis is a mainly lipoprotein-driven disease, which is associated with the formation of atherosclerotic plaques at specific sites of the vascular system through inflammation, necrosis, fibrosis and calcification. In most cases, plaque rupture of a so-called thin-cap fibroatheroma leads to contact of the necrotic core material of the underlying atherosclerotic plaque with blood, resulting in the formation of a thrombus with acute occlusion of the affected (coronary) artery. The atherosclerotic lesions that can cause acute coronary syndromes by formation of a thrombotic occlusion encompass (1) thin-cap fibroatheroma, (2) plaque erosion and (3) so-called calcified nodules in calcified and tortuous arteries of aged individuals. The underlying pathomechanisms remain incompletely understood so far. In this review, the mechanisms of atherosclerotic plaque initiation and progression are discussed.

Ocular perfusion pressure is defined as the difference between arterial and venous pressure in ocular vessels. In practice, mean arterial pressure is used to substitute for arterial pressure in ocular vessels while intraocular pressure gives an estimate for ocular venous pressure. This results in a value that is easy to calculate and which is of importance since several studies have shown that it is correlated to the prevalence, incidence and progression of primary open angle glaucoma. Today, ocular perfusion pressure is used to estimate individual risks. Since no target value for ocular perfusion pressure can be defined, direct therapeutic intervention is difficult. Still, it has to be kept in mind that lowering intraocular pressure automatically leads to an increase in ocular perfusion pressure. The present article also points out problems and limitations in the concept of ocular perfusion pressure and suggests possible solutions for these problems in the future.

In the year 2015, many questions regarding the pathophysiology of essential arterial hypertension remain unresolved. Substantial scientific progress has been made in various medical areas aided by novel molecular"omics" techniques. The findings could then be implemented in diagnostic and therapeutic procedures. In the field of hypertension research such methods have been applied in very large cohorts but have contributed less to pathophysiological understanding and clinical management than expected. The findings on the pathophysiological importance of baroreflex mechanisms, natriuretic peptides and osmotically inactive sodium storage discussed in this article all have something in common: all are based on small, carefully conducted human physiological investigations and often challenge current textbook knowledge. Nevertheless, these findings have opened up new research fields and are likely to affect clinical care.

The ocular perfusion pressure (PP) is presently calculated by subtracting the intraocular pressure (IOP) from the mean ophthalmic artery pressure. In recent years papers have been published in which it has been shown that the pressure in the central retinal vein (CRV) may be higher than the IOP in half the glaucoma patients resulting in a lower perfusion pressure in the retina and in the prelaminar layer of the optic nerve head.A review of these papers is given in which the pulsation of the CRV was assessed or in which the pressure in the CRV has been measured on comparing glaucoma patients and control subjects.By using the Starling resistor as a model the origin of the pulsation of the CRV is explained. The term ophthalmodynamometric force used by Morgan et al. is shown as being the IOP increment given in units of gram-force which may be converted to 0.82 mmHg. Contact lens dynamometry is described.In the five studies published until now the pulsation of the central retinal vein was absent in about half of the glaucoma patients. That is the sign that the pressure in the CRV was higher than the IOP. A worse mean deviation has been found to be strongly predictive of a higher pressure in the CRV. Higher pressures in upper and lower hemiveins were strongly associated with a worse mean deviation in the corresponding hemifields. In the two studies in which the CRV pressure has been measured in mmHg it was up to 25 mmHg higher in the median than the IOP. A Long-term study of 82 months has shown that the pressure in the central retinal vein is strongly predictive of an increase of optic disc excavation.The CRV pressure is often higher in glaucoma patients resulting in a lower PP than assumed until now.

Laser resections of lung metastases are followed by air leaks from the parenchymal defect. Large surfaces after metastasectomy are closed by sutures or sealants while smaller areas are frequently sealed thermally by cautery or laser. In this study two different techniques of thermal sealing of lung tissue with laser light are investigated.Carbonisation of lung tissue during thermal sealing appears at temperatures higher than 180 °C. Hypothetically this is contraproductive to haemo- as well as to pneumostasis. In this experimental study thermal laser sealing with and without carbonisation is investigated. In one series tissue temperatures higher than 100 °C are avoided by water dropping from the tip of the light guide onto the parenchymal leak. In the other series carbonisation appeared because the laser light was applied in the non-contact mode without tissue cooling. The characteristics of the laser were 40 W, 1350 nm continuous mode. Air leaks (Vt) were measured with a simple and fast technique with high precision. The sealing effect of either series was defined as S = (1-Vt/V0) and the difference of S was statistically examined.The basic values V0 before sealing were about the same in both series. The air leaks Vt after 15, 30 and 45 s of sealing varied significantly in both series (p = 0.03). During simultaneous cooling the sealing effect was increasing with the duration of laser application, while it became worse in the series without cooling. Histological examination of the sealing zone showed only coagulation of the tissue, while ruptured alveolae could be seen more often in the non-cooled sealing area.It could be shown in the ex-vivo lung model that laser sealing of parenchymal leaks is improved by simultaneous cooling during laser application. Non cooled laser sealing seems to heat up the tissue abruptly and create carbonisation followed by multiple ruptures of alveola and small airways. In accordance with our clinical experience this experimental study confirms that laser sealing for pneumostasis after metastasectomy can be improved by simultaneously cooling the resection area when treated with the laser.

In recent years a tremendous amount has been learned about the pathophysiology of atrial fibrillation (AF) which induces electrophysiological changes in the right and left atrium. Besides calcium-dependent tissue changes which are induced by activation of proteases and phosphatases, such as calpain and calcineurin, concomitant cardiac diseases activate the atrial angiotensin II system. Experiments have shown positive effects of statins in AF models. In contrast, clinical studies have provided heterogeneous results. Of note, several studies have shown that therapy with angiotensin II receptor blockers or statins does not influence the recurrence of AF.

Friedreich's ataxia is a rare hereditary disease and although the gene defect has already been identified as a deficiency of the mitochondrial protein frataxin, the pathophysiology is still unknown. Although a multisystem disorder organ involvement is predominantly neurological. Besides the characteristic features of spinocerebellar ataxia the heart is frequently also affected. Cardiac involvement typically manifests as hypertrophic cardiomyopathy, which can progress to heart failure and death. So far most research has focused on the neurological aspects and cardiac involvement in Friedreich's ataxia has not been systematically investigated. Thus, a better understanding of the progression of the cardiomyopathy, cardiac complications and long-term cardiac outcome is warranted. Although no specific treatment is available general cardiac therapeutic options for cardiomyopathy should be considered. The current review focuses on clinical and diagnostic features of cardiomyopathy and discusses potential therapeutic developments for Friedreich's ataxia.

The analysis of heart rate variability (HRV) has recently become established as a non-invasive measurement for estimation of demands on the cardiovascular system. The HRV reflects the interaction of the sympathetic and parasympathetic nervous systems and allows the influence of the autonomic nervous system on the regulation of the cardiovascular system to be mathematically described. This review explicates the analysis method of HRV for time, frequency and non-linear methods as well as the range of parameters and the demand on acquisition time. The necessity and possibilities of artefact correction and advice for the selection of a reasonable acquisition period are discussed and standard values for selected HRV parameters are presented.

Acute myocardial infarction remains one of the leading causes of morbidity, mortality and disability in industrialized countries. After an acute myocardial infarction, early and successful myocardial reperfusion is the most effective strategy for reducing the size of a myocardial infarct and improving the clinical outcome. The process of restoring blood flow to the ischemic myocardium, however, can induce injury itself. This phenomenon, termed myocardial ischemia reperfusion injury (IRS), can paradoxically reduce the beneficial effects of myocardial reperfusion. In experimental studies a number of strategies have been shown to ameliorate lethal reperfusion injury. However, the translation of these beneficial effects into the clinical setting has been disappointing. Modulation of the hypoxic nitrate-nitrite-nitric oxide (NO) pathway may have the potential to challenge this problem. First translational studies are promising and clinical trials are ongoing.

Duration and severity of obesity is a risk factor for developing left ventricular dysfunction, manifest cardiac damage and heart failure. To fulfill the increased energy demand with excessive body weight, the organism responds by phyiologic adaptation mechanism such as an increased blood volume, and structural and functional cardiac adaptations. These adaptations result in an increased stroke volume and cardiac output at rest and during exercise. In early stages of obesity an increased cardiac load is resulting in ventricular remodelling and diastolic dysfunction. As obesity becomes chronic a progressive impairment of diastolic and systolic function ensues, and finally a development of left heart failure. Therefore, already in early stages of cardiac overload and left ventricular dysfunction a sufficient and sustainable weight reduction should be targeted avoiding an impairment of diastolic and systolic function and development of heart failure in time.

To be able to evaluate properly a vascular problem, basic concepts of vascular physiology need to be considered, as they have been taught in physiology for a long time. This article deals with selected definitions and laws of passive vascular mechanics, subdivided into parameters of vascular filling and parameters of vascular flow. PARAMETERS OF VASCULAR FILLING: During vascular filling the transmural pressure distends the vascular wall until it is balanced by the wall tension. The extent of this distension up to the point of balance depends on the elasticity of the wall. Transmural pressure, wall tension and elasticity are defined, and their respective importance is described by clinical examples, e.g. aneurysm and varix. PARAMETERS OF VASCULAR FLOW: The vascular flow can be divided into stationary and pulsating components. Both components are relevant for the bloodstream. Since the blood flow is directed in the circuit, it can be understood in first approximation as stationary ("direct current").The direct current model uses only the average values of the pulsating variables. The great advantage of the direct current model is that it can be described with simple laws, which are not valid without reservation, but often allow a first theoretical approach to a vascular problem: Ohm's law, driving pressure, flow resistance, Hagen-Poiseuille law, wall shear stress, law of continuity, Bernoulli's equation and Reynold's number are described and associated with clinical examples.The heart is a pressure-suction pump and produces a pulsating flow, the pulse. The pulse runs with pulse wave velocity, which is much larger than the blood flow velocity, through the arterial vascular system. During propagation, the pulse has to overcome the wave resistance (impedance). Wherever the wave resistance changes, e.g., at vascular bifurcations and in the periphery, it comes to reflections. The incident (forward) and reflected (backward) waves are superimposed to yield the resulting pulse wave. This pulse wave allows one to distinguish pressure and flow pulse by measurement. Both are described separately, and their respective clinical meaning is illustrated by appropriate examples, e.g., arterial stiffness and pre-/postocclusive high/low resistance flow, respectively.

Objectives This study aims to evaluate feasibility, face validity, influence on technical factors and subjective sense of utility of patient-specific rehearsal (PsR) prior to endovascular aortic aneurysm repair (EVAR). Design A prospective, multicentre pilot study. Methods Patients suitable for EVAR were enrolled and a three-dimensional (3D) model of the patient's anatomy was generated. Less than 24 h prior to the real case, rehearsals were conducted in the laboratory or clinical angiosuite. Technical metrics were recorded during both procedures. A subjective questionnaire was used to evaluate realism, technical and human factor aspects (scale 1–5). Results Ten patients were enrolled. In one case, the treatment plan was altered based on PsR. In 7/9 patients, the rehearsal significantly altered the optimal C-arm position for the proximal landing zone and an identical fluoroscopy angle was chosen in the real procedure. All team members found the rehearsal useful for selecting the optimal fluoroscopy angle (median 4). The realism of the EVAR procedure simulation was rated highly (median 4). All team members found the PsR useful to prepare the individual team members and the entire team (median 4). Conclusions PsR for EVAR permits creation of realistic case studies. Subjective evaluation indicates that it may influence optimal C-arm angles and be valuable to prepare the entire team. A randomised controlled trial (RCT) is planned to evaluate how this technology may influence technical and team performance, ultimately leading to improved patient safety.

The repetitive intermittent hypoxic episodes, central nervous arousal and intrathoracic pressure fluctuations that occur together with obstructive sleep apnoea are the primary pathophysiological mechanisms responsible for the cardiovascular co-morbidity. These phenomena lead to increased oxidative stress, systemic inflammation, disrupted vasomotor function, increased sympathetic activity and the development of arteriosclerosis in blood vessels. CPAP therapy lowers arterial blood pressure and has a positive effect on relevant specific aspects of cardiovascular co-morbidity. Until the results of current randomised studies have been published, it has to be decided on an individual basis whether the cardiovascular situation alone justifies CPAP therapy. This will usually be the case in severe OSA with daytime sleepiness, in young patients and patients with good compliance. Interventions that reduce cardiovascular risk and also have a positive effect on OSA, i. e., weight reduction, physical exercise and smoking cessation are always appropriate.

Tako-Tsubo cardiomyopathy (TTC), also referred to as stress cardiomyopathy (SCM), was first described in the 1990s and is characterized by transient left ventricular dysfunction. Its incidence represents 1-2% of all acute coronary syndromes (ACS). In most cases extreme emotional or physical stress precedes this syndrome. The majority of patients affected are postmenopausal women. Since its first description, various hypotheses regarding the pathophysiology of TTC have been discussed. From a historical perspective, coronary vasospasm has often been proposed as a possible cause of this disorder. However, reviews from numerous registries were able to demonstrate that coronary vasospasm plays only a minor role in the pathogenesis of TTC. Several groups showed disturbances in myocardial microcirculation and energy metabolism in the acute phase of TTC. Nevertheless, with regard to the data currently available, it cannot be differentiated whether these changes are the cause or rather the result of TTC. However, recent concepts include an excessive catecholamine overload and morphological changes which are unequivocally documented in TTC. The relation between elevated catecholamine levels and myocardial dysfunction analogous to TTC could be confirmed in animal experiments.In summary, it can be assumed that TTC is caused by an excessive cardiotoxic release of catecholamines. Ventricular dysfunction can be explained by increased numbers of β-adrenergic receptors in the apex, leading to greater vulnerability to catecholamine overload. Individual anatomical differences in the sympathoadrenergic system and distribution from β-adrenergic receptors are presumably responsible for the interindividual occurrence of wall motion abnormalities in TTC.

The slow procession of the primary mechanisms of aging leads, at first, to unnoticed changes in the vascular system. Endothelial dysfunction is one of the earliest markers in aging vessels, caused by oxidative stress via the reduction of the availability of NO, on the one hand, and the nitrosylation of proteins, on the other hand. At the same time, glycation of the proteins of the extracellular matrix leads to stiffening of the vessel wall. Together with the loss of elastic fibers, e.g., elastin, this leads to the age-related changes of the vessels. Knowledge of these primary mechanisms of aging may lead to the development of new drugs.

Heart failure (HF) is a disease with an increasing prevalence and results in both reduced quality of life and decreased lifespan for patients. Despite improved therapy mortality remains very high. HF is induced by events that lead to reduced function of the heart, e.g. myocardial infarction and increased chronic afterload through arterial hypertension. For compensation to occur, neurohumoral mechanisms temporarily maintain cardiac function. Over time this results in left ventricular remodelling and, by means of a vicious circle, compensated HF becomes symptomatic HF. The myocardium of patients with HF is characterised by a dysfunction in excitation-contraction coupling (ECC), which causes reduced cell contractility due to reduced Ca(2+) transients and SR Ca(2+) load. The Ca(2+)/calmodulin-dependent protein kinase IIδ (CaMKIIδ) plays an important role in the onset of HF. CaMKIIδ phosphorylates several functional key proteins, leads to reduced SR Ca(2+) load and Ca(2+)-transients in HF, acts as an arrhythmogenic protein by increasing late I(Na), and contributes to diastolic dysfunction by accumulation of intracellular Ca(2+). CaMKIIδ also plays an important role in atrial fibrillation. Interestingly, with regard to increased cardiac load, CaMKIIδ is activated in increased afterload but not in preload. The important role of CaMKIIδ in HF implies new therapeutic options to improve HF therapy in the future.

The physiological effects of the incretin hormone glucagon-like peptide-(GLP-)1 have contributed to the important role that incretin-based therapies with GLP-1 analogs or dipeptidyl peptidase-(DPP-)4 inhibitors already play in type 2 diabetes treatment. This development is not only due to the glucose-dependent insulinotropic effect of GLP-1 as well as the positive effects on beta cell function and, probably, beta cell mass, but also to the beneficial effects on body weight.Lately, the data on positive cardiovascular effects of GLP-1 have been growing. In animal models, GLP-1 improves left ventricular function and diminishes myocardial defects in ischemia models. In clinical studies with GLP-1 analogs, a normalization of blood pressure was observed and some of the data from animal studies after myocardial infarction or after invasive cardiologic or cardiosurgical interventions were also found under clinical conditions in humans. Additionally, an improvement of cardiovascular surrogate parameters was observed with incretin-based therapies. This review gives an overview on the cardiovascular effects of GLP-1 and incretin-based therapies.

There is no question that cholesterol, especially low-density lipoprotein (LDL) cholesterol, represent a major cardiovascular risk factor. The so-called lipid hypothesis has been proven by almost all epidemiologic studies, animal studies and, most importantly, by interventional studies with lipid-lowering drugs, especially statins. However, despite our better understanding of atherogenesis we cannot explain why atherosclerosis occurs most frequently and severely on coronary arteries rather than on other arteries such as those of the hands or feet. In addition, the "lipid hypothesis" is unable to explain the dramatic change in severity of a far more generalized atherosclerosis in patients suffering from diabetes mellitus.Recently, we studied the effects of fatty acids on endothelial integrity and found a dramatic increase in apoptosis under fatty acid exposition. Since it is well known that the heart depends highly on fatty acid delivery to cover its energy demand, we hypothesize that the heart becomes the victim of its energy demand. With the so-called Marburg hypothesis of atherogenesis we can explain the fact why especially the arteries of the heart show early atherosclerotic lesions, but also the fact why patients with diabetes develop more generalized atherosclerosis. Finding mechanisms to reduce the presence of fatty acids within the arterial wall might prevent plaque destabilization and could be a potential target in our fight against atherosclerosis.

The metabolic syndrome is usually associated with insulin resistance and visceral fat distribution, which appear to play a direct role in the development of clinical criteria of metabolic syndrome, like elevation of arterial blood pressure and dyslipidemia. In this review, the authors will first introduce the concept, that insulin resistance and increased visceral adipose tissue are also regularly associated with an abnormal or ectopic accumulation of lipids in nonadipocytes, like steatosis hepatis. Then, they will provide some evidence that epicardial fat can be associated with insulin resistance in a similar fashion as visceral intraabdominal fat. Furthermore, epicardial fat might directly affect the vessels and function of the heart. Accordingly, ectopic accumulation of fat within cardiac muscle cells can impair their function and possibly be related to heart failure. These new relations between obesity, fat distribution and cardiac function might help to identify and treat individuals at risk earlier and more appropriately.

Ventricular tachycardias (VT) associated with the His-Purkinje system may occur in patients with and without organic heart disease. The former may encounter bundle branch reentrant VT, a macroreentrant VT utilizing the specific conduction system. It frequently occurs in patients with preexisting conduction disturbance such as complete left bundle branch block and may be eliminated by catheter ablation of the right bundle branch. After successful ablation, patient's prognosis depends on the presence or absence of structural heart disease.In patients without structural heart disease, VT with right bundle branch block pattern and superior axis, referred to as idiopathic left ventricular tachycardia, is observed. It is a reentrant VT utilizing the posterior left fascicle and the Purkinje network. The two treatment options include antiarrhythmic drug therapy with verapamil or curative catheter ablation.Another form of ventricular arrhythmia originating in the Purkinje network is idiopathic ventricular fibrillation (IVF). Focal triggers from the right and left ventricular Purkinje network induce premature ventricular contractions inducing IVF. This is amenable to catheter ablation leading to a significant reduction in ICD (implantable cardioverter defibrillator) interventions in sudden cardiac death survivors.

The thin-walled right heart is characterized by a low mass-volume-relation. Right ventricular function is influenced basically by loading conditions (afterload and preload), myocardial perfusion, contractility and heart rate. Afterload is determined by intrathoracal and pulmonary vascular pressure/resistance. Morphologic adaptions of the right ventricle affect right ventricular function in cor pulmonale. So the normal, not hypertrophied right ventricle is extremely sensitive to increasing pulmonary artery pressure. Otherwise, minor reductions in afterload lead to a substantial decrease of right ventricular wall stress, myocardial oxygen demand and likely the risk of arrhythmia. Therefore clinical consequences and complications of pulmonary hypertension are substantially dependent on right ventricular dynamics.

Dronedarone is recommended as the successor drug to amiodarone because a faster onset of effects and less side effects are to be expected. This review describes the pharmacological properties of this multi-channel blocker and summarizes the results from recent studies proving successful antiarrhythmic therapy using dronedarone in patients with atrial fibrillation.

Inhibition of coagulation is a key therapeutic principle in acute coronary syndromes (ACS). A plethora of substances is used in daily clinical practice to prevent thrombocyte aggregation, i.e. primary haemostasis, as well as activation of the coagulation cascade. Prevention of thrombocyte aggregation is accomplished by inhibiting thromboxane synthesis by acetyl salicylic acid, blockade of the ADP receptor, and by inhibition of the glycoprotein IIb/IIIa-receptor. Inhibition of the plasmatic coagulation in the setting of acute coronary syndromes is primarily achieved by the use of unfractionated or low-molecular weight heparins. Beyond this, several next-generation substances such as the novel, potent ADP receptor antagonist prasurgel or the selective direct thrombin- and factor Xa-antagonists are being developed and are investigated in clinical trials. It remains to be determined which place these novel substances will take in the armentarium of anticoagulants in acute coronary syndromes, and whether they will be employed in the majority of ACS-patients or just in certain sub-populations (e.g., in patients with a high or a low bleeding risk, in the presence of aspirin- or clopidogrel resistance etc.). The current review summarizes the mode of action as well as the clinical use of currently employed anticoagulants in acute coronary syndromes.

Arterial hypertension leads to cardiac restructuring and damage. This "hypertensive heart disease" includes left ventricular hypertrophy. In addition, it is also considered responsible for diastolic and systolic dysfunction, vascular manifestations of microangiopathy and in a broader sense also coronary heart disease as well as cardiac dysrhythmias and sudden cardiac death. The pathophysiological mechanisms depend on a complex neurohumoral regulation and the ensuing change in cardiac structure and output. The initial compensation for increased cardiac demand is followed by permanent heart damage and successive decompensation. At this point the typical complaints involved in cardiac insufficiency or ischemia become evident. Determining the diagnosis is particularly important early on since the prognosis with regard to morbidity and mortality deteriorates if the hypertensive condition persists and the heart develops lasting damage.

Phase contrast MRI allows access to tri-directional encoded velocity information and therefore, measurement of flow in the human hemodynamic system. The aim of this work was to investigate whether this technology could be applied to support the grading of stenosis in mid-size arteries. Using a specially constructed flow phantom and a stenosis model with tube diameter of 5mm and 8mm and a stenosis of 50%, experiments at different flow rates (180-640 ml/min), slice thickness (1-4 mm), field strength (1.5 and 3.0 T), and multi-slice as well as 3D volume acquisition were performed. The observations were assessed visually and evaluated by signal-to-noise (SNR) ratios in regions before and after the stenosis. The obtained results show that examinations should be performed at high field (3.0 T) and at flow rates up to 500 ml/min without hampering the measurements by areas of signal loss. In comparison, no detectable differences in the flow patterns of the two acquisition schemes could be observed. However, the SNR was higher using the 3D volume acquisition and thick slices. In summary, 3D PC-MRI of mid-size vessels with stenosis is feasible for certain flow rates. The presented results could be seen as guidance for in vivo situations to assess if an examination of a patient is reasonable in terms of outcome.

Fluid dynamics play an important role in arterial diseases. PC-velocimetry as a magnetic resonance (MR) method is a useful tool for the examination of blood vessels, in particular in haemodynamics and morphology. Due to signal loss caused by turbulent flow, classification of stenoses remains difficult. In the presence of metallic stents, susceptibility effects and RF-artefacts further deteriorate image quality.Regarding fluid dynamics, stenosis, stent and restenosis (i.e., re-closing of the vessel in areas with stents) have similar properties: the flow close to an obstacle is accelerated and after a specific length, the so-called reattachment length, it redevelops into its original flow profile. Depending on the shape of the obstacle and its reattachment length, a method is developed to classify stenosis using MR-imaging. Enlarged, simplified stenosis models (phantoms) were examined and were also modelled using computational fluid dynamics (CFD).MR- and CFD-measurements show influences of the stenosis shape, especially the diameter. In graphical analysis (streamline and vector plots), a reattachment length of 6.7xstep size could be determined under laminar conditions and nonpulsatile flow.Stenosis and other narrowing of vessels are classifiable more exactly using PC-velocimetry. From the flow behaviour in the area around the narrowing of the vessel wall, the character of the stenosis can be derived. But more parameters, as bended vessel shapes, pulsated flow, non-Newtonian flow behaviour as well as elastic properties of the vessels need to be incorporated.

Severe arterial hypertension is a hallmark of Cushing syndrome which occurs in 80% of the patients. Additionally, persistent cortisol excess induces obesity, hyperinsulinemia with disturbed glucose tolerance and dyslipidemia which all contribute to the development of hypertension and its deleterious sequelae. Cortisol effects are mediated through diversely distributed intracellular glucocorticoid and mineralocorticoid receptors which are protected by the 11-beta-hydroxysteroiddehydrogenase type 2 in cells of some organs (i.e. kidney) but not in other. A highly complex clinical picture evolves in case of hypercortisolism due to the ubiquitous distribution of steroid receptors with different affinity and binding capacities for glucocorticoids. The present review focuses on the cortisol induced changes in blood pressure regulation which contribute to the development of hypertension.

After disastrous outcomes due to wear-induced osteolysis in the 1980s, hip resurfacing arthroplasty has undergone a renaissance, mainly because of the introduction of metal-on-metal bearings. However, there are still problems associated with this technique, such as femoral neck fractures, neck thinning, and aseptic loosening, and their causes are still being investigated. During the last years, increasing evidence has shown that both the frequently used posterior approach to the hip as well as preparation of the femoral epiphysis can impair blood supply to the femoral head. In the presence of mechanical stresses (impaction, heat development during cement polymerization) during the implantation, the epiphysis might not be able to compensate for this. This paper summarizes the current understanding of the blood supply to the femoral head and proposes a way to preserve the viability after hip resurfacing.

Atrial fibrillation, venous thromboembolism, and valvular heart disease are the most common indications for treatment with anticoagulants. Regarding the high incidence of these diseases, it can be assumed that about 1% of the population takes oral anticoagulants. Approximately one third of the patients hospitalized in a surgical clinic receive vitamin K antagonists. Hence, general practitioners and specialists in hospitals as well as in private practice are constantly faced with different options of anticoagulatory treatment. In numerous situations, inhibitors of coagulation exhibit a substantial benefit. However, this is only achieved by accepting an increased risk of bleeding. To walk the tightrope between too much and insufficient anticoagulatory action is an important challenge in clinical practice. Knowledge of the mechanisms underlying pharmacological anticoagulation is crucial in order to evaluate the indications for and efficiently manage anticoagulant therapy. Ideally, the aim of an adequate anticoagulation should be to guarantee sufficient hemostasis in combination with simultaneous prevention of thrombus formation. This article intends to provide an overview of the coagulation system and established as well as novel pharmacological targets.

The goal of numeric analysis of aortic blood flow is to evaluate the mechanisms leading to an aortic aneurysm with regard to the risk of a rupture and to describe the effect of interventional therapy. Numeric analysis is based on virtual models of vascular structures and the physical characteristics of the vessel wall, of blood as fluidum, and the blood flow. Using this information, numeric analysis solves the appropriate equations. The results can be displayed quantitatively and qualitatively. The results of numeric flow simulation show that in abdominal aortic aneurysms the wall pressure, which is of vital importance for the risk of rupture, depends on several factors, one being the location of the intraluminal thrombus. In models of aneurysms after stent grafting, numeric analysis can be used to evaluate factors leading to stent migration. Although numeric analysis of aortic blood flow still has several limitations, recent studies have shown that this method has the potential for improved estimation of the rupture risk of aortic aneurysms in the near future.

Until today, there is no reliable criterion to predict the risk of rupture of abdominal aortic aneurysms (AAAs), which could help in the final clinical decision. The acceptance of the traditional diameter criterion has led to unnecessary surgical procedures with the subsequent high mortality and morbidity. On the other hand, small aneurysms are known that sometimes are subject to rupture, which could be avoided in the case of an early surgical decision. Thus, it becomes necessary to find new criteria, which can reliably predict the actual risk of rupture of AAAs in the clinical setting. This prediction will certainly be a useful clinical tool in the management of patients with AAAs. According to the biomechanical approach in predicting the risk of aneurysm rupture and to the fundamental principles in cardiovascular mechanics, rupture occurs when the AAA wall stresses exceed the failure strength of the wall. Therefore, it becomes obvious that the knowledge of the distribution of stress on a particular AAA wall would be a good indication of its susceptibility to rupture. A methodology to noninvasively determine the in vivo distribution of stresses on the AAA wall is therefore necessary.

Chronic heart failure is a clinical syndrome and the final common pathway of different cardiac diseases. Heart failure is accompanied by activation of the renin-angiotensin-aldosterone-system and the adrenergic nervous system. In addition, recent data emphasize important roles of maladaptive intracellular signaling pathways, decreased capillary density, altered calcium handling, metabolic changes, genetic polymorphisms, and programmed cell death in the failing heart. In this context, traditional pathophysiological concepts, e. g. concerning the role of cardiac hypertrophy, had to be given up. Thus, an increasingly complex scenario emerges with interdependent changes on the biochemical, molecular, metabolic, and cellular level. Novel therapeutic strategies may soon be based on these new pathophysiological concepts.

Cardiovascular diseases such as coronary heart disease are the leading cause for morbidity and mortality in industrial countries. Current evidence shows that stiffening of the arterial wall is one major mechanism responsible for this morbidity and mortality in cardiovascular disease. Various physiological and pathophysiological parameters influence arterial stiffening including age, gender, blood pressure, smoking, and diseases such as hypertension, diabetes, renal failure, and hypercholesterolemia. Thus, the assessment of arterial stiffness has become a widely used tool to investigate the function of the arteries in epidemiologic and clinical studies. Traditionally, arterial stiffness has been assessed by pulse wave velocity, a noninvasive parameter which has been shown to predict cardiovascular mortality. In addition, pulse wave analysis has been increasingly used to determine the augmentation index, a parameter that describes the effect of pulse wave reflection on the central aortic pressure configuration. In the present review, the pathophysiological contribution of arterial stiffening for cardiovascular morbidity and mortality is described. Details of models, indices, and techniques used to evaluate stiffness will be presented. Clinical studies investigating the predictive value of stiffness markers in defining future cardiovascular risk and survival are summarized.

Calcific aortic valve stenosis is the most common valvular heart disease in the elderly. Although the diagnosis can often be assumed at clinical presentation, determination of the disease severity is usually not accurately possible based on patient history and physical examination alone. In the past, invasive cardiac catheterization has been the most important strategy for assessing the hemodynamic severity of aortic stenosis. Nowadays, Doppler echocardiography has largely replaced invasive catheterization in many centers, since this modality allows for a comprehensive evaluation of the morphological and functional characteristics of the stenotic valve and for assessment of the prognosis of the disease. This article summarizes the current knowledge on the evaluation of aortic stenosis severity using Doppler echocardiography.

Introduction Experiments on animals have underlined the importance of vascularisation for biointegration and functionality of any given tissue engineering device. The aim of this investigation was to dissect the angiogenetic process in the frame of axial neovascularisation of a xenogenic solid matrix. The ultimate goal of this series of studies is the application of cells onto a prevascularised matrix, with the ambition to enhance cell survival after transplantation in vivo. Materials and methods We performed a study in the rat with different vascular configurations in an isolation chamber. A disc-formed biogenic hard matrix (9 x 5 mm) was encased into an isolation chamber made of Teflon. In group 1, an arteriovenous fistula (AV loop) between the femoral vessels was microsurgically constructed and was placed around the matrix (n = 15). In group 2, the vascular carrier had the form of an arteriovenous ligated pedicle (n = 15). Evaluation intervals were two, four and eight weeks after implantation. The modes of evaluation included histology, scanning electron microscopy of corrosion casts as well as intravital micro-magnetic resonance imaging (MRI). Results The arteriovenous loop as vascular carrier revealed a higher capacity for angiogenesis over the bundle configuration. The neo-fibrovascular tissue displayed minimal inflammatory elements but dense vascularisation. Scanning electron microscopy demonstrated a vivid angiogenesis with rapid evolution of the vascular bead into mature, hierarchically organised network. Micro-MRI could be used for serial investigation in terms of flow measurements and detection of thrombosis. Discussion The presence of a vascular bed prior to cell transplantation might protect against hypoxia-induced cellular death, especially at central portions of the matrix, and therefore ensure physiological function of the device. The generation of vascularised bioartificial tissue substitutes might offer new modalities of surgical reconstruction for use in reparative medicine.

The endothelium is of important significance in the development of the acute coronary syndrome. As an endo-/paracrine organ, the endothelium plays a key role in the regulation of the vascular homeostasis. The endothelial integrity and above all the bioavailability of nitric oxide (NO) are essential for the correct function of the endothelium. Cardiac risk factors may lead to an endothelial dysfunction with a consecutive imbalance of the vascular homeostasis. In an inflammatory or prothrombotic state the endothelium shows a number of abnormalities such as oxidative stress, expression of cell adhesion molecules, activation of cell signal-systems (renin-angiotensin-system, CD40/CD40L-system) and especially the loss of NO. The inflammatory cascades lead to coronary atherosclerosis over years or, more instantly, to the acute coronary syndrome caused by endothelial erosion or the rupture of an instable plaque. The knowledge of the pathophysiological processes in the arterial wall during the acute coronary syndrome may lead to the identification of high risk patients and the development of more targeted therapies.

During the last ten years we have made substantial progress in our understanding of the underlying mechanisms of atrial fibrillation. The high rate associated alterations in electrical and structural properties of the atria, referred to as atrial remodeling, promote the progression of atrial fibrillation. The development of new therapeutic approaches addresses three different directions: (i) prevention of atrial remodeling, especially of structural remodeling; (ii) increase of long-term efficacy of currently used drugs and improvement of their side-effect profile; and (iii) design of atria- and pathology-specific antiarrhythmic drugs without concomitant proarrhythmic effects in the ventricles. The current review outlines the pathophysiology of atrial fibrillation and focuses on electrical remodeling. The properties of new antiarrhythmic drugs for atrial fibrillation are discussed in detail.