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In dieser prospektiven klinischen Studie konnte der bereits in der Literatur beschriebene positive Effekt der peripheren Vasodilatation nach Anlage eines Plexuskatheters nachgewiesen und quantifiziert werden. Die Arbeit dient als Vorstudie einer möglichen zukünftigen Optimierung der postoperativen Phase hinsichtlich der Überwachung und der Verbesserung der Durchblutungssituation bei Replantationen. Die Studie bediente sich eines Patientenkollektivs von 20 Patienten, die im Rahmen einer Operation zur Behandlung einer Rhizarthrose standardmäßig einen Plexuskatheter bekamen. Mit Hilfe der non-invasiven Messungen des O2C®-Geräts konnte die Veränderung verschiedener Blutflussparameter in der Mikrozirkulation erfasst werden. Gemessen wurden jeweils die relative Sauerstoffsättigung im Gewebe (SO2), die relative Hämoglobinmenge (rHb), der Blutfluss (Flow) und die Blutflussgeschwindigkeit (Velocity) in einer Gewebetiefe von 8mm. Über 72 Stunden wurden nach Anlage des Plexuskatheters regelmäßige Messzeitpunkte gesetzt. Es konnten der vasodilatatorische Effekt des Plexuskatheters durch Sympathikolyse in der Mikrozirkulation darstellt und quantifiziert werden. Der Blutfluss wurde um bis zu 146% gesteigert, die Sauerstoffsättigung stieg um 35% an. Direkt nach Anlage des Plexuskatheters konnte ein Anstieg in allen 4 Parametern für vier bis sechs Stunden postoperativ festgestellt werden. Danach näherten sich die Werte denen der Kontrollhand an. Dieser Effekt trat auf, obwohl die Therapie über den Plexuskatheter fortgesetzt wurde. Die bisher in der Literatur beschriebenen Studien sind entweder in der zeitlichen oder im Umfang der gemessenen Parameter begrenzt. Meist werden die Modifikationen der Mikrozirkulation deskriptiv als „Nebenwirkungen“ der Plexusanästhesie dargestellt. Daher sind sie nur begrenzt dazu geeignet einen eventuellen therapeutischen Nutzen abzuleiten. In der vorliegenden Arbeit konnte erstmals ein Systematischer Überblick über die Veränderungen verschiedener Aspekte der Mikrozirkulation im Langzeitverlauf berichtet werden. Die dadurch gefundenen Daten lassen sich zur Entwicklung eines neuen klinischen Therapiekonzeptes nutzen. Weitere Untersuchung sind erforderlich um die klinische Signifikanz eines solchen Konzeptes zu beurteilen.

This CME article addresses the pathophysiology, incidence, current survival outcome and treatment options for patients with cardiogenic shock as a complication of acute myocardial infarction. The shock spiral of left heart failure due to cardiac infarction, subsequent vasoconstriction and paradoxical vasodilation due to the systemic inflammation response syndrome (SIRS) is a vicious circle which must be interrupted. Treatment focuses on the evidence from randomized clinical trials and the current guideline recommendations. With respect to interventional and surgical treatment the question of culprit lesion vs. complete revascularization is still unsolved. For medicinal treatment acetylsalicylic acid (ASA) and heparin are more often supplemented with prasugrel and ticagrelor. In the case of inotropes, dobutamine remains the first-line treatment option and for vasopressors norepinephrine. The calcium sensitizer levosimendan has not provided the hoped for superiority over conventional treatment in randomized trials. The use of intra-aortic balloon pumps (IABP) is no longer recommended as circulatory support in acute heart failure (reduced to class III). The use of percutaneous implantable mechanical circulatory support devices has not shown a survival benefit in the few randomized trials carried out so far even when compared with IABP, due to increased bleeding complications.

For thousands of years, cocoa have been a very popular food and has been linked to various beneficial health effects. Observational and epidemiological studies point towards a beneficial effect of dark chocolate on cardiovascular morbidity. Several small, albeit controlled studies indeed demonstrate an amelioration of endothelial dysfunction - the dysfunction of the inner layer of the vessels - after intake of dark, flavanol-rich chocolate. This is important, as endothelial dysfunction is an important marker of the development of atherosclerosis and an important prognosticator of future cardiovascular events. This article summarizes the actual literature in this respect.Seit Jahrtausenden ist Kakao ein beliebtes Nahrungsmittel, dem eine gesundheitsfördernde Wirkung nachgesagt wird. Beobachtungsstudien sowie grosse epidemiologische Studien weisen auf eine mögliche günstige Wirkung von dunkler Schokolade auf die kardiovaskuläre Gesundheit hin. Mehrere kleine kontrollierte Studien zeigen tatsächlich eine Verbesserung der endothelialen Dysfunktion – also der Verbesserung der Fehlfunktion der Gefässinnenschicht – nach Einnahme von dunkler, Flavanol-reicher Schokolade. Dies ist insbesondere deshalb wichtig, da eine gestörte Endothelfunktion ein wichtiger Marker für die Entstehung der Atherosklerose und eine wichtige Vorhersage für kardiovaskuläre Ereignisse ist. Dieser Artikel fasst die akutelle Literatur zusammen.Pendant des milliers d'années, le cacao a été une nourriture très populaire et liée à divers effets bénéfiques sur la santé. Les études d'observation et épidémiologiques pointent vers un effet bénéfique du chocolat noir sur la morbidité cardiovasculaire. Plusieurs petites études démontrent clairement une amélioration de la dysfonction endothéliale – le dysfonctionnement de la couche interne des vaisseaux – après la prise de chocolat noir, riche en flavanols. Cette dysfonction est importante, comme l'endothélium est un marqueur important de l'évolution de l'athérosclérose et un facteur pronostique important de futurs événements cardiovasculaires. Cet article vise à résumer la littérature à cet égard.

Patients suffering from septic shock often present with not only severe reduction of afterload induced by vasodilation but are also affected by sepsis-induced cardiac dysfunction. Elevated troponin levels, which are typically not caused by coronary ischemia, may indicate septic cardiomyopathy which is characterized both by altered systolic function as well as by disturbances in the regulation of heart rate and heart rate variability. The latter findings are based not only on the dysfunction of the autonomous nervous system but are also the result of the direct interaction of endotoxins with cardiac pacemaker cells. In order to quantify the extent of septic cardiomyopathy, cardiac output has to be considered in the light of the existing afterload, i.e., by the parameter 'afterload-related cardiac performance' (ACP). Therapy of septic shock (and thereby septic cardiomyopathy) is based on the well-known causative, supportive, and adjunctive strategies. Stabilization of cardiac function is assured by volume resuscitation (including blood transfusion) and inotropic support (dobutamine). Further specific therapeutic approaches have not yet been established.

Type 2 diabetic patients have an increased level of systemic free radicals, which severely restrict the bioavailability of endothelium-derived nitric oxide (NO) and thus contribute to the development of an endothelial dysfunction. This review analyses the influence of physical training on molecular development mechanisms of the endothelial dysfunction and determines the significance of regular physical exercise for the endothelial function in type 2 diabetic patients. Systematic training reinforces the endogenic antioxidative capacity and results in a reduction in oxidative stress. Training - also combined with a change in diet - furthermore reduces hyperglycaemic blood sugar levels, thus curbing a major source of free radicals in diabetes. Moreover, physical exercise enhances vascular NO synthesis through an increased availability/activity of endothelial NO synthases (eNOS). Endurance, as well as resistance training with submaximal intensity or a combination of both forms of training is suitable to effectively improve the endothelial function in type 2 diabetic patients in the long term.

Spinal cord stimulation (SCS) has been successfully used to treat chronic pain syndromes for decades. For this purpose, an electrode is implanted into the epidural space under local anaesthesia and connected to a neurostimulator which applies a weak direct current to the dorsal roots of the spinal column. Besides pain control, SCS increases the blood supply in the stimulated area. This effect is mediated by a sympathicolytic effect and the liberation of vasodilatators within the stimulated skin area. A Cochrane meta-analysis has revealed a significantly increased limb salvage rate in patients with non-reconstructable critical limb ischaemia (CLI) treated with SCS. The effect of SCS in CLI might be predicted by the measurement of forefoot transcutaneous pO (2) in supine and dependent positions, which renders trial stimulation unnecessary in many cases.

In blood vessels, the endothelium is a crucial signal transduction interface in control of vascular tone and blood pressure to ensure energy and oxygen supply according to the organs needs. In response to vasoactive factors and to shear stress elicited by blood flow, the endothelium secretes vasodilating or vasocontracting autacoids, which adjust the contractile state of the smooth muscle. In endothelial sensing of shear stress, the osmo- and mechanosensitive Ca(2+)-permeable TRPV4 channel has been proposed to be candidate mechanosensor. Using TRPV4(-/-) mice, we now investigated whether the absence of endothelial TRPV4 alters shear-stress-induced arterial vasodilation. In TRPV4(-/-) mice, loss of the TRPV4 protein was confirmed by Western blot, immunohistochemistry and by in situ-patch-clamp techniques in carotid artery endothelial cells (CAEC). Endothelium-dependent vasodilation was determined by pressure myography in carotid arteries (CA) from TRPV4(-/-) mice and wild-type littermates (WT). In WT CAEC, TRPV4 currents could be elicited by TRPV4 activators 4alpha-phorbol-12,13-didecanoate (4alphaPDD), arachidonic acid (AA), and by hypotonic cell swelling (HTS). In striking contrast, in TRPV4(-/-) mice, 4alphaPDD did not produce currents and currents elicited by AA and HTS were significantly reduced. 4alphaPDD caused a robust and endothelium-dependent vasodilation in WT mice, again conspicuously absent in TRPV4(-/-) mice. Shear stress-induced vasodilation could readily be evoked in WT, but was completely eliminated in TRPV4(-/-) mice. In addition, flow/reperfusion-induced vasodilation was significantly reduced in TRPV4(-/-) vs. WT mice. Vasodilation in response to acetylcholine, vasoconstriction in response to phenylephrine, and passive mechanical compliance did not differ between genotypes, greatly underscoring the specificity of the above trpv4-dependent phenotype for physiologically relevant shear stress. Genetically encoded loss-of-function of trpv4 results in a loss of shear stress-induced vasodilation, a response pattern critically dependent on endothelial TRPV4 expression. Thus, Ca(2+)-influx through endothelial TRPV4 channels is a molecular mechanism contributing significantly to endothelial mechanotransduction., Endotheliale Ionenkanäle und insbesondere Ca2+-permeable Kationenkanäle vom TRP-Typ sollen eine wichtige Rolle für die Endothelfunktion spielen, indem sie einen Calciumeinstrom erzeugen und somit wichtige Vasodilatationsysteme wie das NO-system und das EDHF-system stimulieren. Ziel der vorliegenden Arbeit war es, die funktionelle Bedeutung von osmo- und potentiell mechanosensitiven TRPV4-Kanälen für endotheliale Vasodilatationsprozesse zu charakterisieren. Hierzu sollten genetisch manipulierte Mäuse, denen das TRPV4-Protein fehlt, und korrespondiere Wildtyp-Tiere verwendet werden und vergleichende elektrophysiologische Untersuchungen an Endothelzellen und gefäßphysiologische Untersuchungen zur Endothelfunktion mittels des Druckmyographen durchgeführt werden. Die vergleichenden elektrophysiologischen Untersuchungen an Endothelzellen der A.c.c. von TRPV4+/+- und TRPV4-/--Tieren zeigten, dass TRPV4 AA- induzierte und HTS-induzierte Ströme wesentlich vermittelt. Die gefäßphysiologischen Befunde stellten heraus, dass durch Wandschubspannung und durch Reperfusion hervorgerufene Vasodilatation der Arteria carotis communis bei den TRPV4-/--Mäusen fehlten. Im Gegensatz dazu traten bezüglich der vom glatten Gefäßmuskel abhängigen SNP-vermittelten und der Azetylcholin-induzierten Vasodilatation zwischen TRPV4-/-- und WT- Mäusen keine Unterschiede auf. Diese Hauptbefunde der vorliegenden Arbeit legen nahe, dass endotheliale TRPV4-Kanäle eine essentielle Signaltransduktionskomponente bei der endothelialen Mechanotransduktion darstellen. Es kann ferner spekuliert werden, dass durch eine pharmakologische Modulation von endothelialen TRPV4-Kanälen der arterielle Gefäßtonus manipuliert werden kann. Dies könnte einen pharmakologischen Ansatzpunkt für eine neuartige antihypertensive Therapieform darstellen.

Hypertension can be classified based on certain criteria, such as severity, existence of specific end-organ damage, or the dominant blood pressure subphenotype so that isolated diastolic hypertension (IDH), mixed systolic-diastolic hypertension (SDH), and isolated systolic hypertensive (ISH) states can be defined. The FRAMINGHAM study was the first to demonstrate a continuous increase of systolic blood pressure with age and a peak of diastolic pressure between 55 and 65 years of age. This results not only in a high prevalence of hypertension of approximately 50-80% beyond the age of 60 but also in a disproportionately high increase in isolated systolic hypertension. ISH develops either as a new condition mostly from the group of primary high-normal blood pressure or secondly through burnout of existing systolic-diastolic hypertension with highly progressive vascular ageing.The pathophysiological background lies in remodeling processes in the macrovascular and microvascular compartments with stiffening of conduit and peripheral arterial vessels. In clinical practice these processes are easy to measure by determining pulse wave velocity (PWV), the augmentation index, and pulse pressure. These parameters are closely related to cardiovascular and cerebrovascular morbidity and mortality ISH is not only a hypertension subphenotype but often indicates significant organ damage or may even be considered to be a secondary form of hypertension characterized by remodeled and stiffened arterial vessel walls and this condition is difficult to treat. It appears therefore that ISH warrants special therapeutic strategies with a focus on antiproliferative, antistiffening, anti-atherosclerotic, and vasodilating actions. As a result of the available data from the results of treatment studies it appears that renin-angiotensin system (RAS) blockers and calcium channel blockers (CCBs) are the preferred drugs for treatment of this condition.

Since the first description of the "endothelium-derived relaxing factor" (EDRF) in 1980 the function of the endothelium has developed into a field of research of its own. The most important endothelial factor is nitric oxide (NO), which is formed from l-arginine with the help of NO synthase (NOS). Disturbances of the endothelial function play an important role in men's health such as atherogenesis and erectile dysfunction and are also followed by morphological vessel changes. Furthermore, NO seems to play an important role in LUTS (lower urinary tract symptoms) and male fertility.

Arginine vasopressin (AVP) is increasingly being used to treat advanced vasodilatory shock states due to sepsis, systemic inflammatory response syndrome (SIRS) or after cardiac surgery. There are currently no data available on long-term survival.Demographic and clinical data, length of intensive care unit (ICU) stay, 1-year survival and causes of death after ICU discharge of 201 patients who received AVP because of advanced vasodilatory shock were collected retrospectively.The intensive care unit (ICU) survival rate was 39.8% (80 out of 201 patients). After ICU discharge 13 out of the 80 patients died within 1 year resulting in a 1-year survival rate of 33.3% (67 out of 201 patients). In nine patients, the cause of death was attributed to the same disease that led to ICU admission. One-year survival of patients with shock following cardiac surgery (42.1%) was higher than in patients suffering from SIRS (22.6%, p=0.005) or sepsis (28.3%, p=0.06).If advanced vasodilatory shock can be reversed with AVP and patients can be discharged alive from the ICU, 1-year survival rates appear to be reasonable despite severe multi-organ dysfunction syndrome (MODS).

The acute respiratory distress syndrome (ARDS) is characterized by a maldistribution of pulmonary blood flow towards non-ventilated atelectatic lung areas being the main reason for intrapulmonary right-to-left shunt with the consequence of severe arterial hypoxemia. The application of inhaled nitric oxide (iNO) is a therapeutic option to selectively influence pulmonary blood flow in order to improve arterial oxygenation and to decrease pulmonary artery pressure without relevant systemic side effects. Although randomized controlled trials demonstrated no survival benefit in patient populations covering the entire severity range of acute lung injury, iNO represents a feasible rescue treatment for ARDS patients with severe refractory hypoxemia and is, therefore, an important option for ARDS therapy in specialized centers.

Organic nitrates still are one of the most important drug classes used in the treatment of an acute coronary syndrome and stable coronary artery disease as well as acute and chronic congestive heart failure. The mechanism of vasodilatation comprises the release of nitric oxide, which in turn activates soluble guanylate cyclase and lowers the intracellular calcium content leading to relaxation of vascular smooth muscle. Recent research has demonstrated that highly reactive nitrates, such as nitroglycerin (or glyceryl trinitrate) and pentaerthrityl tetranitrate (PETN) are bioactivated by aldehyde dehydrogenase 2 (ALDH-2), an enzyme located in mitochondria. The enzyme, which bioactivates mono- and dinitrates is not yet identified. Despite being effective in the acute treatment of patients, its long-term efficacy is limited by the development of tolerance to nitrates and of endothelial dysfunction. Both of these side effects of nitrate therapy are due to increased production of reactive oxygen species. This review focuses on new aspects of the process of bioactivation of organic nitrates, the conception of oxidative stress of endothelial dysfunction and of the development of tolerance and their therapeutic consequences. Also discussed are more recent findings on nitric oxide donors such as molsidomine, PETN and the combination treatment of isosorbide dinitrate and hydralazine of patients with coronary artery disease and chronic heart failure.

In this study we examined the arterial-adaptive dilatation and Doppler velocimetry, especially RI values, in normal fetuses with a single umbilical artery (SUA).We studied 195 fetuses from 18 to 39 weeks of gestational age with a prenatally identified SUA retrospectively. They were enrolled in this study if the following information applied:18 weeks of gestational age, no structural or chromosomal abnormalities, and histopathological confirmation of SUA. Sonographic examination included evaluation of the umbilical artery resistance and the cross-sectional area of the umbilical cord, and its vessels were measured in all cases. Small for gestational age (SGA) was diagnosed when the birth weight was below the 10th percentile for gestational age. Fetuses with intrauterine growth restriction were defined as those with biometric data below the 5th percentile.There were 119 cases of prenatally identified SUA which met the inclusion criteria. RI values were below the 10th percentile in 33/119 (27.33) and below the 50th percentile in 73/119 (61.33). RI values below the 10th percentile were significantly more likely to be in the normal collective than in the growth restricted collective [31/87 (35.63%) vs. 2/32 (6.25%); p = 0.001]. Even more significant differences became apparent when comparing the RI values below the 50th percentile of both groups. An umbilical artery diameter over the 90th percentile was found in 49 (41.9%) of cases and was significantly more likely to be present in normal growing fetuses than in the growth restricted group.Normal fetuses with SUA are at higher risk to be born as SGA. With our study results we can confirm the hypothesis that Doppler flow measurements and arterial diameter in SUA are different from those found in normal fetal umbilical arteries. RI values over the 50th percentile or a cross-sectional area of the artery below 95th percentile after 26th week of gestation significantly increases the risk of SGA.

Migraine pathophysiology is determined by genetic and environmental factors. Based on altered cerebral habituation and low serotonin levels, certain triggers can elicit a migraine attack. Following initial unspecific prodromi, an aura follows in many patients which most often consists of visual symptoms. Cortical spreading depression is the electrophysiological correlate of the aura and can activate the trigemino-vascular system. This is one potential mechanism initiating the pain process. The characteristic unilateral pulsating headache is caused by a neurogenic inflammation in the meninges. Neck pain as reported by some patients is a migraine-specific feature, the anatomical basis being the trigemino-cervical complex. Functional changes in the pain processing system maintain the headache. Among these are sensitization of trigeminal nucleus caudalis neurons and an altered antinociception descending from the periaquaductal grey. Triptans have a peripheral and central mode of action, but they are no longer effective once central sensitization has occurred.

Sinusoidal alterations unrelated to primary hepatocellular damage present without characteristic clinical findings and in these cases the liver biopsy is particularly important. Capillarization of sinusoids is characterized by closing of fenestration, formation of a basal membrane and by the expression of CD34 and is typical for active cirrhosis. In nodular regeneratory hyperplasia, capillarization indicates a local or general disturbance of perfusion. In large regenerative nodules, focal nodular hyperplasia and liver cell adenoma CD34-positive capillaries reflect afferent parts and CD34-negative sinusoids the efferent parts of the parenchymal vascular bed. HCC generally have a completely capillarized CD34-positive vascular bed. Hepatic angiosarcomas and epithelioid hemangioendotheliomas can be easily overseen in liver biopsies, if they spread along the sinusoids without detoriation of the acinar architecture and without significant alteration of the surrounding liver cell plates. Toxic damage of endothelial cells, post-sinusoidal stasis and sinusoidal hyperperfusion are the underlying pathogenetic principles of sinusoidal injury. Rupture and loss of the perisinusoidal reticulin fibres lead to peliosis hepatis. In these cases liver biopsy might disclose occlusion of the terminal liver veins (VOD). Perisinusoidal fibrosis can be caused by intrasinusoidal accumulation of pathologic cells, advanced intrasinusoidal macrophagocytic storage diseases and by activation of the vitamin A-storing hepatic stellate cells. Perisinusoidal amyloidosis can be the first sign of an underlying B-cell neoplasia.

Increased sympathetic nervous activity which induces vasoconstriction and decreases perfusion may be an underlying mechanism behind the development of perioperative liver damage. This animal study was designed to assess how clonidine-induced systemic sympathicolysis affects liver oxygenation with respect to induced hypotension and vasodilatation under physiological conditions.Following ethical approval 17 anesthetized and acutely instrumented pigs were randomly assigned to 2 groups. Group 1 consisted of 8 animals receiving intravenous clonidine (2 microg x kg(-1) bolus and 2 microg x kg(-1) x h(-1) for induction of sympathicolysis and group 2 consisted of 9 animals serving as controls. After obtaining baseline values, measurements were repeated 90 and 250 min after starting to reduce systemic sympathetic nervous activity.Clonidine-induced systemic sympathicolysis was associated with decreased mean arterial blood pressure, cardiac output and heart rate. Portal venous and hepatic arterial blood flow, oxygen delivery to the liver, oxygen uptake and liver tissue oxygen partial pressure remained unchanged. The plasma indocyanine green disappearance rate increased.We concluded that despite decreased mean arterial pressure and cardiac output, clonidine-induced systemic sympathicolysis did not affect liver oxygenation or perfusion.

The severe impairment of the microcirculation plays a substantial role in the pathogenesis of severe sepsis and septic shock, and leads to multiple organ failure and death. Therapeutic strategies to resuscitate the microcirculatory blood flow and to improve the functional capillar density are therefore essential to surmount the microcirculatory pathology and to avoid tissue hypoxia. Based on reasonable scientific evidence, early fluid resuscitation directed by defined haemodynamic and metabolic goals (EGDT) as well as the application of activated protein C (rhAPC) according to the guidelines could be recommended. Dobutamine is the first choice to improve cardiac output and to overcome myocardial depression in septic shock whereas phosphodiesterase-III-inhibitors and levosimendane are still experimental options. Furthermore selective inhibitors of iNOS, nitroglycerol, as well as vasopressin have to be investigated relating to their specific effects on the microcirculation and their influence on survival in seevere sepsis and septic shock.

The past few years have witnessed a remarkable advance in our understanding of the pathophysiology of coronary heart disease. Myocardial ischemia usually occurs on the basis of coronary atherosclerosis. Although the functional consequences of depriving the myocardium of its blood supply have been appreciated for many years, coronary heart disease is still the leading cause of morbidity and mortality in the western world. This has focused the attention of physicians on restoring blood flow to the ischemic region in order to prevent tissue necrosis and regain organ function. Reperfusion of ischemic tissues is often associated with microvascular dysfunction that is manifested as impaired endothelial-dependent dilatation in arterioles and leukocyte plugging in capillaries. The availability of a broad variety of knockout mice provides important clues about the progression of the ischemia/reperfusion (I/R) injury. Therefore mouse models for I/R are of great importance for the development of new therapeutic strategies for humans.

Hepatorenal syndrome (HRS) is a serious complication of end-stage liver disease that was associated with a fatal prognosis in the past. A clear definition of HRS and increased understanding of the pathogenesis have led to considerable progress in therapy outcome.The major pathogenetic factor is vasodilation of the mesenteric circulation with arterial underfilling and consecutive renal vasoconstriction.Restoration of an effective arterial blood volume can be achieved by the combination of vasopressor therapy (terlipressin, norepinephrine), in combination with volume expansion (albumin) with a success rate of up to 75%. Restoration of the effective arterial blood volume may also be achieved by implantation of a transjugular intrahepatic portosystemic stent (TIPS). This has also been successful in up to 50% of patients in selected cohorts. Finally, extracorporeal liver support systems based on exchange or detoxification of albumin have been successfully employed in a number of patients. Liver transplantation remains the only principal therapy of HRS as this is the single measure with a curative intent. All other forms of therapy are palliative but may serve as a bridge to liver transplantation.

The retinal vessel analyzer (RVA) offers the unique opportunity for noninvasive online measurements of the "Bayliss effect." In the presented study this myogenic response is used to test vessel contractility of retinal arterioles in different stages of diabetic retinopathy (DR).Forty patients with diabetes were exposed to a standardized rise in blood pressure. The myogenic response of a retinal arteriole was measured by continuous use of the RVA during this time. The subjects were divided into four groups (each n=10) according to different stages of DR. Group I: no DR, group II: mild/moderate DR, group III: moderate/severe nonproliferative DR with laser treatment, and group IV: proliferative DR with laser treatment.A similar blood pressure rise was achieved in all subjects. In response to this BP rise, group I demonstrated a vasoconstriction of -7.6% (+/-4.1). In group II -0.85% (+/-4.3) and in group III a mild vasodilation of +0.44% (+/-5.9) was found. Group IV presented a vasodilatation of +3.2% (+/-5.9).According to the progression of the morphological changes in diabetic retinopathy a functional deficit in the autoregulation of retinal arterioles can be measured with the RVA.

The term "coronary ectasia" describes the dilatation of one or more coronary artery segments with the signs of an impaired coronary blood flow. The prevalence, clinical significance and necessity of treatment of such a lesion is unclear.Diagnostic coronary angiographies of 7101 patients (2131 women and 4970 men) were retrospectively evaluated for the presence of dilated coronary segments. Prevalence, age- and gender distribution, cardiovascular risk factors, clinical symptoms, CRP-concentrations, prevalence of myocardial infarction as well as the coronary morphology of patients with coronary ectasia were studied. The occurrence of myocardial infarction in this group was compared to that in a control group consisting of patients with stenotic coronary artery disease.The prevalence of coronary ecstasy was 1.4 % (women: 0.56 %; men: 1.79 %), mean age of patients was 63.5 +/- 10.5 years. The right coronary artery was most frequently involved (RCA: 97 %, LAD: 30 %, RCX: 23 %, LCA: 35 %). In patients with one-vessel disease the right coronary artery was exclusively affected. In 85.1 % the dilatation of coronary segments was associated with stenotic coronary artery disease. 73.3 % of the patients with coronary ectasias suffered from angina, 33.7 % CCS (Canadian Cardiovascular Society) class III and IV. Angina in patients with coronary ecstasy did not differ from that of patients with stenotic coronary artery disease only. Patients with coronary ectasias had a higher incidence of myocardial infarction than patients with stenotic coronary heart disease (p0.001).Coronary ectasia is a relatively rare entity and often associated with stenosis. Angina is a common symptom. Patients with coronary ectasias seem to suffer more frequently from myocardial infarctions than patients with only stenotic coronary heart disease.

The study investigated the variance of the retinal vessel response to flicker light between the right and left eyes and after a short and a medium-length time interval.The prospective study included 28 volunteers. In the first exam both eyes were examined. One eye selected randomly was measured again after 1 h and after 1 month. The diameter response of an arterial and venous vessel segment was measured continuously by a Dynamic Vessel Analyzer (DVA, IMEDOS, Jena). Each examination consisted of 50 s baseline measurement and three periods of 20-s flicker light provocation followed by 80 s observation. The mean of three provocational cycles was calculated as dynamic vessel response.A significant correlation of the flicker response parameters between the right and left eyes was found. Arterial and venous baseline diameter, flicker light dilation, AVDQ, and BP did not change significantly between the first and follow-up examinations. There was no correlation between changes of BP and changes of vessel diameter parameters in the follow-up exams.Flicker-evoked dilation of retinal arterioles measured by the DVA is characterized under similar conditions by small variance after short and medium-length time periods. Therefore, this parameter is suitable as a functional parameter of the regulation ability of retinal arteries.

The aim of this study was to compare the diameter response of retinal arteries and veins after provocation with flickering light regarding the amplitude and temporal course.The study included 26 healthy volunteers. The vessel diameter was automatically and continuously measured by the retinal vessel analyzer. The examination consisted of a baseline measurement (100 s) followed by five periods of 20-s flicker light provocation and 80-s follow-up observation.A diameter dilation was observed immediately after the end of the flicker period in arteries (6.9+/-2.8%) and veins (6.5+/-2.8%, difference n.s.). The quotient of arterial and venous dilation (AVDQ) was 1.25+/-0.69 (range: 0.2-2.8). A significant correlation of age and arterial or venous dilation or the AVDQ was not observed. The arterial diameter reduced faster than the venous and reached a minimum of -2.7+/-1.4% at 25.9+/-10.8 s after the end of the flicker phase. The veins were dilated by 0.5+/-1.3% at the time of the maximal individual arterial constriction (p0.0001).Flicker-evoked response of retinal arteries and veins did not differ in the dilative amplitude but in the temporal course of the abatement of the dilation.

Endothelial dysfunction is a "systemic disease" and a predictor of preclinical atherosclerosis. A relatively simple-to-perform and reliable diagnostic method of evaluating endothelial function is the measurement of the forearm blood flow (FBF). Unremarkable vasoreactivity of the brachial artery on performing FBF measurement is a prognostically favorable sign. This applies equally to patients with cardiovascular risk factors such as hypertension, hyperlipidemia or diabetes mellitus, and to patients with angina pectoris. A number of investigations suggest that cardiovascular endpoints can be significantly diminished by reducing the risk factors.

In order to lower arterial blood pressure, antihypertensive drugs decrease cardiac output, total peripheral resistance or both. Diuretics, beta-blockers, and central adrenergic inhibitors decrease cardiac output. ACE inhibitors, angiotensin II antagonists, calcium antagonists, alpha-blockers, central adrenergic inhibitors, and after a delay also diuretics and beta-blockers decrease peripheral resistance. Diuretics are first line therapy for treating low renin hypertension. Beta blockers are used for treating high renin hypertension and patients suffering additional coronary artery disease. ACE inihibitors can be given for treating high renin hypertension particularly in conjunction with diabetes, heart failure or left ventricular hypertrophy. Combining ACE inhibitors with diuretics potentiates the antihypertensive effect. Angiotensin II antagonists exert fewer side effects and better renal protection than ACE inhibitors. The main indication for calcium antagonists is low renin hypertension, their advantages being strong blood pressure reduction as well as in preventing stroke. Central alpha2 receptor agonists and other vasodilators are chosen only in selected cases and mostly in combination with other antihypertensive drugs.

One-lung ventilation is frequently used in thoracic surgery. However, hypoxic pulmonary vasoconstriction of the atelectatic lung may produce pulmonary hypertension. The objective of the present study was to compare the acute effects of intravenous versus aerosolized prostacyclin (PGI(2)) on pulmonary and systemic circulation.PGI(2) was administered in 11 anesthetized and unilaterally ventilated pigs by infusion (5, 10, and 20 ng/kg body weight/min) and by inhalation (4, 8, and 16 ng/kg body weight/min) in a cross-over design.Infusion of PGI(2) reduced both pulmonary (PVR) and systemic vascular resistance (SVR). Due to a concomitant increase in cardiac index (CI) mean arterial (MAP) and pulmonary artery pressures (MPAP) did not change significantly. In contrast, aerosolized PGI(2) produced a significant decrease in PVR (-21.4 to -32.8%) and MPAP (-12.0 to -17.8%) without affecting SVR, MAP, and CI. Arterial oxygenation tension (p(a)O(2)) was not affected.During one-lung ventilation only aerosolized prostacyclin produced a selective pulmonary vasodilation.

Ageing is one of the most important cardiovascular risk factors. Vascular ageing is determined by genetic, mechanic and hemodynamic factors. The latter is strengthened by the fact that age-associated changes in capillaries and veins, vessels which are less prone to changes in pulsatility and blood pressure, are less pronounced or even absent. Age-related morphologic changes in large resistance vessels include an intima-media thickening, increased deposition of matrix substances, thus ultimately leading to a reduced compliance. Vascular ageing is mainly characterized by an impaired endothelium-dependent vasorelaxation. The expression of endothelial nitric oxide synthase (eNOS), producing vasodilatatory nitric oxide (NO), is markedly upregulated with increasing age. However, vasorelaxation is impaired, as the production of reactive oxygen species such as superoxide (O2-), concomitantly increases. NO and O2- react to form the powerful oxidant peroxynitrite (ONOO-). Peroxynitrite is known to initiate oxidative modification of proteins, including nitration of aromatic rings, thereby rendering functionally inactive certain regulatory proteins. Deposition of nitrated proteins is mainly found within endothelial mitochondria, suggesting that mitochondrial dysfunction plays a major role in the vascular ageing process. It yet remains to be shown whether oxidative stress, which is, according to the currently accepted "oxidative stress hypothesis", a key event of vascular ageing, can be pharmacologically prevented, e.g. by naturally occurring antioxidant vitamins. However, in a mammalian model of ageing, an unexpected accumulation of vitamin E was found to accumulate within the aortic wall. This may represent a self-regulatory adaptive mechanism to prevent age-associated oxidative stress. In contrast, ascorbic acid was found to decrease with increasing age. Eventually, it remains to be seen if vitamin C or other antioxidative substances may be useful therapies. Statins and ACE inhibitors are known to have effects on mechanisms interfering with the ageing process. Given the strong age-dependency of cardiovascular disease, the developments of therapies to delay vascular ageing might have enormous medical (and economic) consequences in the future.

Pharmacologic stress with adenosine is frequently used for noninvasive detection of coronary artery disease. Dietary intake of caffeinated food, beverages or medications might alter adenosine-induced hyperemic blood flow, thereby compromising the diagnostic sensitivity of adenosine stress testing. In this case we report on a male patient with CAD. Myocardial blood flow at rest and during adenosine-induced hyperemia 2 hours after consumption of decaffeinated coffee and again without caffeine intake were quantified by ammonia PET. After caffeine intake there was a clearly diminished increase of myocardial blood flow during adenosine. The average coronary flow reserve in the myocardium was 1.3 after caffeine. In the baseline study without caffeine the coronary flow reserve has been improved to 2.3. Caffeine intake alters the coronary vasodilatory capacity. These findings emphasize the importance of carefully screening patients for intake of caffeinated food prior to adenosine stress testing.

Ketamine was shown to increase coronary blood flow. It was the aim of this study to answer the question whether ketamine directly dilates coronary arteries.Using the model of isolated vessel rings we studied the effects of ketamine (2.5, 25, and 250 microg ml(-1)) on the contractile response to three vasoconstrictors, acetylcholine, histamine, and serotonin in porcine coronary artery segments. Other rings were contracted with KCl or PGF (2a) and then treated with ketamine (5 up to 500 microg ml(-1) added cumulatively).Ketamine dose-dependently dilated coronary arteries in concentrations beyond those used in clinical practice. In intact rings ketamine racemate (250 microg ml(-1)) attenuated contractions mediated by acetylcholine by 38.8 +/- 2.8%, histamine by 33.0 +/- 4.4% and serotonin by 42.1 +/- 3.7% (p0.05). There were no differences between intact and denuded rings (acetylcholine 38.5 +/- 2.8%, histamine 26.6 +/- 4.7%, serotonin 30.0 +/- 3.2%). With low concentrations of ketamine (2.5 microg ml(-1)) a slight tendency towards a contraction was recorded (n. s.). In rings precontracted with either KCl or PGF (2a) ketamine caused a small enhancement of contraction (KCl: 101.4 +/- 0.4%, PGF (2a): 101.3 +/- 1.4%) when administered in low concentration (5 microg ml(-1)), but almost complete relaxation (KCl: 0.4 +/- 1.3%, PGF (2a): 0.0 +/- 5.4%) in high concentration (500 microg ml(-1)).It is concluded that ketamine dose-dependently dilates porcine coronary arteries in concentrations beyond those used in clinical practice and that this effect is independent of endothelial function.

Primary headache syndromes, such as cluster and migraine, are widely described as vascular headaches, even though there is considerable clinical evidence to suggest that both conditions are primarily central, that is regulated by the brain. The shared anatomical and physiological substrate for both clinical syndromes is the neural innervation of the cranial circulation. Early functional imaging using PET has shed light on the genesis of both syndromes, documenting activation in the midbrain and pons in migraine and in the hypothalamic gray in cluster headache. These areas are involved in the pain process in a permissive or triggering manner rather than simply as a response to first-division nociceptive pain impulses. This article reviews findings in the physiology of the trigeminovascular system which demand renewed consideration of the neural influences in many primary headaches and the physiology of the neural innervation of cranial circulation. Primary headaches should thus be regarded as neurovascular headaches to emphasize the interaction between nerves and vessels which is their underlying characteristic.