Hyaluronidase treatment of coronary glycocalyx increases reactive hyperemia but not adenosine hyperemia in dog hearts

VanTeeffelen, Jurgen W. G. E.; Dekker, Simone E.; Fokkema, Dirk S.; Siebes, Maria; Vink, Hans; Spaan, Jos A. E.

doi:10.1152/ajpheart.00446.2005

Cited by 25 publications

(42 citation statements)

References 34 publications

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“…Because the vessels proximal from the site of observation have very low vasomotor tone in these experiments, 28 the resistance decrease must be confined to the distal microvessels and possibly reflects an increase in perfused microvascular volume resulting from glycocalyx degradation. 38,39 …”

Section: Glycocalyx and Shear Dependent Vasodilationmentioning

confidence: 99%

Heparin Impairs Glycocalyx Barrier Properties and Attenuates Shear Dependent Vasodilation in Mice

et al. 2007

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Abstract-The endothelial glycocalyx is a hydrated mesh of polysaccharides and adsorbed plasma proteins that forms the true interface between the flowing blood and the endothelium. We hypothesized in the present study that competitive binding of heparin to glycocalyx-associated proteins would affect glycocalyx barrier properties and mechanotransduction of shear stress to the endothelium. In anesthetized mice, the clearance of 70-kDa dextrans from the circulation was increased (PϽ0.05 versus saline) 1 hour after heparin (1.25 U) and glycocalyx degradation with hyaluronidase (35 U; amount cleared in 30 minutes after saline: 11Ϯ5%; after heparin: 45Ϯ8%; after hyaluronidase: 30Ϯ3%). Clearance of 40-kDa dextrans increased (PϽ0.05 versus saline) to a lesser extent after both treatments (saline: 46Ϯ3%; heparin: 60Ϯ5%; hyaluronidase: 60Ϯ2%). The dilator response of second-order arterioles in cremaster muscle during reactive hyperemia was reduced for Յ90 minutes after heparin as reflected by a decrease (Pϭ0.008) in t 50 of diameter recovery, and this effect was associated with a diminished NO bioavailability. Infusion of hyaluronidase resulted in reductions (PϽ0.05) in baseline and peak reactive hyperemic diameter, whereas, despite an increase in wall shear rate at the beginning of reactive hyperemia, t 50 of diameter recovery was not affected. In conclusion, our data in mice show that a heparin challenge is associated with increased vascular leakage of dextrans and impaired arteriolar vasodilation during reactive hyperemia. Our data suggest that protein-heparan sulfate interactions are important for a functional glycocalyx.

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Section: Glycocalyx and Shear Dependent Vasodilationmentioning

confidence: 99%

Heparin Impairs Glycocalyx Barrier Properties and Attenuates Shear Dependent Vasodilation in Mice

et al. 2007

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“…Because of the limited access of flowing blood to an intact glycocalyx, microvascular blood volume might therefore in effect be reduced by as much as 50% of available anatomical microvascular volume due to glycocalyx presence. Others have demonstrated that enzymatic treatment of the glycocalyx with, for example, heparinase or hyaluronidase (9,11,35) and also exposure of the glycocalyx to the vasodilators adenosine, bradykinin and sodium nitroprusside (21,31,38,41) increases glycocalyx porosity for plasma macromolecules and red blood cells. However, measurements of the effect of attenuated glycocalyx barrier properties on potential increases in coronary blood volume have never been performed.…”

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confidence: 99%

Acute attenuation of glycocalyx barrier properties increases coronary blood volume independently of coronary flow reserve

Brands

Spaan²,

Vink

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Vascular endothelium is covered with an extensive mesh of glycocalyx constituents, which acts like an effective barrier up to several micrometers thick that shields the luminal surface of the vasculature from direct exposure to flowing blood. Many studies report that various enzymatic and pharmaceutical challenges are able to increase glycocalyx porosity, resulting in farther permeation of plasma macromolecules and greater access of red blood cells into glycocalyx domain. Attenuation of glycocalyx barrier properties therefore potentially increases the amount of blood that effectively occupies available microvascular volume. We tested in the present study whether attenuation of coronary glycocalyx barrier properties actually increases coronary blood volume and whether such changes would be noticeable during measurements of coronary flow reserve using adenosine. In anesthetized goats (n = 6) with cannulated left main coronary artery that were perfused under controlled pressure, coronary blood volume was measured via the indicator-dilution technique using high-molecular-weight (2,000 kDa) dextrans as plasma tracer and labeled red blood cells as red blood cell tracer. Coronary blood volume was determined at baseline and during intracoronary infusion of adenosine causing maximal vasodilation (0.2-0.6 mg.kg(-1).h(-1)) before and after intracoronary hyaluronidase treatment (170,000 units) of the glycocalyx. With an intact glycocalyx, coronary blood volume was 18.9 +/- 1.1 ml/100 g heart tissue at baseline, which increased to 26.3 +/- 2.7 ml/100 g after hyaluronidase treatment of the coronary glycocalyx. Maximal vasodilation by administration of adenosine further increased coronary blood volume to 33.9 +/- 6.8 ml/100 g, a value not different from the maximal coronary blood volume of 33.2 +/- 5.3 ml/100 g obtained by administration of adenosine in the absence of hyaluronidase treatment. Adenosine-induced increases in coronary conductance were not affected by hyaluronidase treatment. We conclude that acute attenuation of glycocalyx barrier properties increases coronary blood volume by approximately 40%, which is of similar magnitude as additional changes in coronary blood volume during subsequent maximal vasodilation with adenosine. Furthermore, maximal coronary blood volume following administration of adenosine was similar with and without prior hyaluronidase degradation of the glycocalyx, suggesting that adenosine and hyaluronidase potentially increase glycocalyx porosity to a similar extent. Hyaluronidase-mediated changes in coronary blood volume did not affect baseline and adenosine-induced increases in coronary conductance, demonstrating that measurements of coronary flow reserve are insufficient to detect impairment of coronary blood volume recruitment in conditions of damaged glycocalyx.

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“…Apart from pathological conditions, glycocalyx thickness can change also because of increased shear stress (even at atherosclerosis-prone sites) and in response to agonists such as adenosine, which may increase wall conductivity up to 40% [51].…”

Section: Simulation Of Glycocalyx Sheddingmentioning

confidence: 99%

Modeling Loss of Microvascular Wall Homeostasis during Glycocalyx Deterioration and Hypertension that Impacts Plasma Filtration and Solute Exchange

Facchini

Bellin²,

Toro³

2016

CNR

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Abstract:The fiber matrix of the surface glycocalyx layer internally coating the endothelial cells and plugging the intercellular clefts is crucial for microvascular wall homeostasis. Disruption of the glycocalyx is found in clinical conditions characterized by microvascular and endothelial dysfunction such as atherosclerosis, diabetes mellitus, chronic renal failure and cerebrovascular disease. Shedding of its components may also occur during oxidative stress and systemic inflammatory states including septis. In this work, we investigate the effects of glycocalyx degradation, either due to enzymatic digestion or to agonist recruitment, on plasma filtration and solute extravasation. We also take into account the possibility of a physiological or pathological increase in blood pressure, as in hypertensive zones such as pre-and post-stenotic blood vessels. Our mathematical model shows that a seriously damaged glycocalyx produces an augmentation of flux of both solvent and solute, thus losing its role of transport barrier and macro-molecular sieve, in agreement with experimental evidence. Similarly, hypertension causes an increase in both volume and solute fluxes, also according to physiological findings. The combination of glycocalyx deterioration and hypertension further raises plasma and solute fluxes, potentially leading in most severe cases to edema and hemorrhage, as in the case of diabetes.

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Hyaluronidase treatment of coronary glycocalyx increases reactive hyperemia but not adenosine hyperemia in dog hearts

Cited by 25 publications

References 34 publications

Heparin Impairs Glycocalyx Barrier Properties and Attenuates Shear Dependent Vasodilation in Mice

Heparin Impairs Glycocalyx Barrier Properties and Attenuates Shear Dependent Vasodilation in Mice

Acute attenuation of glycocalyx barrier properties increases coronary blood volume independently of coronary flow reserve

Modeling Loss of Microvascular Wall Homeostasis during Glycocalyx Deterioration and Hypertension that Impacts Plasma Filtration and Solute Exchange

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