Endothelial Glycocalyx.

The endothelial glycocalyx (EG) is the most luminal layer of the blood vessel, growing on and within the vascular wall. Shedding of the EG plays a central role in many critical illnesses. Degradation of the EG is associated with increased morbidity and mortality.

Non-invasive evaluation of macro- and microhemodynamic changes during induction of general anesthesia - A prospective observational single-blinded trial.

Background: Hypotension and bradycardia are known side effects of general anesthesia, while little is known about further macro- and microhemodynamic changes during induction. Intriguing is furthermore, why some patients require no vasopressor medication to uphold mean arterial pressure, while others need vasopressor support.

Objective: Determination of macro- and microhemodynamic changes during induction of general anesthesia.

Preinterventional hydrocortisone sustains the endothelial glycocalyx in cardiac surgery.

Background: Patients undergoing cardiac surgery commonly develop systemic inflammation associated with tissue edema, which impairs outcome. One main pathomechanism leading to the edema is the deterioration of the endothelial glycocalyx, a key component of the vascular barrier. In animal models hydrocortisone has proved to be protective for the glycocalyx.

Chances and limitations of isolated mouse heart models for investigating the endothelial glycocalyx1.

Background: The endothelial glycocalyx plays a decisive role in maintaining vascular homeostasis. Previous animal models have mainly focused on in-vitro experiments or the isolated beating guinea pig heart. To further evaluate underlying mechanisms of up- and down regulation, knock-out animals seem to be a promising option.

Vascular Endothelial Dysfunction during Cardiac Surgery: On-Pump versus Off-Pump Coronary Surgery.

Background: Cardiac surgery often causes ischemia and development of a systemic inflammatory response syndrome, which impairs vascular barrier function, normally maintained by the endothelial cell line and the endothelial glycocalyx (EG). The EG normally covers and protects healthy endothelial cells throughout the vasculature. The aim of the present study was to assess the disruption of the cellular part of the microvascular barrier by determining parameters of endothelial cell activation known to influence and reflect cell-cell junctional integrity.

Sevoflurane mitigates shedding of hyaluronan from the coronary endothelium, also during ischemia/reperfusion: an ex vivo animal study.

Glycosaminoglycan hyaluronan (HA), a major constituent of the endothelial glycocalyx, helps to maintain vascular integrity. Preconditioning the heart with volatile anesthetic agents protects against ischemia/reperfusion injury. We investigated a possible protective effect of sevoflurane on the glycocalyx, especially on HA.

Regulation of blood flow and volume exchange across the microcirculation.

Oxygen delivery to cells is the basic prerequisite of life. Within the human body, an ingenious oxygen delivery system, comprising steps of convection and diffusion from the upper airways via the lungs and the cardiovascular system to the microvascular area, bridges the gap between oxygen in the outside airspace and the interstitial space around the cells. However, the complexity of this evolutionary development makes us prone to pathophysiological problems.

Degradation of the endothelial glycocalyx in clinical settings: searching for the sheddases.

The endothelial glycocalyx has a profound influence at the vascular wall on the transmission of shear stress, on the maintenance of a selective permeability barrier and a low hydraulic conductivity, and on attenuating firm adhesion of blood leukocytes and platelets. Major constituents of the glycocalyx, including syndecans, heparan sulphates and hyaluronan, are shed from the endothelial surface under various acute and chronic clinical conditions, the best characterized being ischaemia and hypoxia, sepsis and inflammation, atherosclerosis, diabetes, renal disease and haemorrhagic viral infections. Damage has also been detected by in vivo microscopic techniques.

Acute degradation of the endothelial glycocalyx in infants undergoing cardiac surgical procedures.

Background: There is no doubt today about the existence of the endothelial glycocalyx (EG) and its decisive role in maintaining vascular homeostasis in adult humans. Shedding of the EG has been demonstrated in adults with sepsis or trauma, in patients undergoing major operations, and after ischemia/reperfusion. The aim of the present study was to demonstrate whether shedding of the EG also occurs in infants undergoing heart operations.

Hypervolemia increases release of atrial natriuretic peptide and shedding of the endothelial glycocalyx.

Introduction: Acute normovolemic hemodilution (ANH) and volume loading (VL) are standard blood-sparing procedures. However, VL is associated with hypervolemia, which may cause tissue edema, cardiopulmonary complications and a prolonged hospital stay. The body reacts to hypervolemia with release of atrial natriuretic peptide (ANP) from the heart.

Protection of glycocalyx decreases platelet adhesion after ischaemia/reperfusion: an animal study.

Background: Strategies targeting the protection of the vascular barrier, in particular the endothelial glycocalyx, are subjects of current research. Antithrombin III and hydrocortisone have been shown to reduce shedding of the glycocalyx following ischaemia/reperfusion. Platelet adhesion to endothelial cells is one consequence of ischaemia/reperfusion.

The impact of crystalloidal and colloidal infusion preparations on coronary vascular integrity, interstitial oedema and cardiac performance in isolated hearts.

Introduction: Recent data suggested an interaction between plasma constituents and the endothelial glycocalyx to be relevant for vascular barrier function. This might be negatively influenced by infusion solutions, depending on ionic composition, pH and binding properties. The present study evaluated such an influence of current artificial preparations.

Physiological levels of A-, B- and C-type natriuretic peptide shed the endothelial glycocalyx and enhance vascular permeability.

Atrial natriuretic peptide (ANP) is a peptide hormone released from the cardiac atria during hypervolemia. Though named for its well-known renal effect, ANP has been demonstrated to acutely increase vascular permeability in vivo. Experimentally, this phenomenon was associated with a marked shedding of the endothelial glycocalyx, at least for supraphysiological intravascular concentrations.

Ischemia-reperfusion-induced unmeasured anion generation and glycocalyx shedding: sevoflurane versus propofol anesthesia.

Introduction: Vascular leakage after ischemia-reperfusion (IR) is largely attributed to the destruction of the endothelial barrier and its associated negatively charged glycocalyx. In vitro, sevoflurane attenuates these changes. Therefore, we compared sevoflurane with propofol with regard to the protection of the glycocalyx and the release of negatively charged substances in vivo.

Mitochondrial thioredoxin reductase is essential for early postischemic myocardial protection.

Background: Excessive formation of reactive oxygen species contributes to tissue injury and functional deterioration after myocardial ischemia/reperfusion. Especially, mitochondrial reactive oxygen species are capable of opening the mitochondrial permeability transition pore, a harmful event in cardiac ischemia/reperfusion. Thioredoxins are key players in the cardiac defense against oxidative stress.

Release of atrial natriuretic peptide precedes shedding of the endothelial glycocalyx equally in patients undergoing on- and off-pump coronary artery bypass surgery.

The present study investigates why shedding of the endothelial glycocalyx occurs both in patients undergoing on- and off-pump coronary artery bypass surgery. Release of atrial natriuretic peptide (ANP) was of special interest, because ANP initiates shedding ex vivo. Three major constituents of the glycocalyx (syndecan-1, heparan sulfate and hyaluronan) were measured in arterial blood of patients undergoing coronary artery bypass surgery with (n = 15) and without (n = 15) cardiopulmonary bypass at various phases of the procedure.

Perspectives in microvascular fluid handling: does the distribution of coagulation factors in human myocardium comply with plasma extravasation in venular coronary segments?

Background: Heterogeneity of vascular permeability has been suggested for the coronary system. Whereas arteriolar and capillary segments are tight, plasma proteins pass readily into the interstitial space at venular sites. Fittingly, lymphatic fluid is able to coagulate.

Endothelial glycocalyx and coronary vascular permeability: the fringe benefit.

Current concepts of vascular permeability are largely still based on the Starling principle of 1896. Starling's contribution to understanding vascular fluid homeostasis comes from realising that the transport of fluid to and from the interstitial space of peripheral tissues follows the balance between opposing oncotic and hydrostatic pressures. It is presumed that in peripheral tissues fluid is readily filtered from blood to tissues at the arterial/arteriolar side of the circulation and largely reabsorbed at the venular/venous aspect, excess fluid being removed from the tissue by the lymphatic system.

Therapeutic strategies targeting the endothelial glycocalyx: acute deficits, but great potential.

Damage of the endothelial glycocalyx, which ranges from 200 to 2000 nm in thickness, decreases vascular barrier function and leads to protein extravasation and tissue oedema, loss of nutritional blood flow, and an increase in platelet and leucocyte adhesion. Thus, its protection or the restoration of an already damaged glycocalyx seems to be a promising therapeutic target both in an acute critical care setting and in the treatment of chronic vascular disease. Drugs that can specifically increase the synthesis of glycocalyx components, refurbish it, or selectively prevent its enzymatic degradation do not seem to be available.

The glycocalyx of the human umbilical vein endothelial cell: an impressive structure ex vivo but not in culture.

Potter and Damiano recently assessed the hydrodynamic dimensions of the endothelial glycocalyx in vivo (mouse cremaster muscle venules) and in vitro (human umbilical vein and bovine aorta endothelium cultured in perfused microchannels) using fluorescent microparticle image velocimetry (Circ Res. 2008;102:770-776). Great discrepancy was observed, the glycocalyx presenting a zone of interaction extending approximately 0.

Albumin augmentation improves condition of guinea pig hearts after 4 hr of cold ischemia.

Background: Major causes of death after heart transplantation are right ventricular pump failure and, chronically, cardiac allograft vasculopathy. Traditional preservation techniques focus on immediate cardioplegia, without particularly considering vascular demands. Recently, the endothelial surface layer, composed of the endothelial glycocalyx and plasma proteins, was discovered to play a major role in vascular barrier function, edema formation, and leukocyte-to-endothelial interaction.