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

1 Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht; and Departments of 2 Medical Physics and 3 Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Submitted December 18, 2008 ; accepted in final form...

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Published in:American journal of physiology. Heart and circulatory physiology 2010-02, Vol.298 (2), p.H515-H523
Main Authors: Brands, Judith, Spaan, Jos A. E, Van den Berg, Bernard M, Vink, Hans, VanTeeffelen, Jurgen W. G. E
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description 1 Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht; and Departments of 2 Medical Physics and 3 Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Submitted December 18, 2008 ; accepted in final form November 23, 2009 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 40%, which is of similar magnitude as additional changes in coronary blood v
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E ; Van den Berg, Bernard M ; Vink, Hans ; VanTeeffelen, Jurgen W. G. E</creator><creatorcontrib>Brands, Judith ; Spaan, Jos A. E ; Van den Berg, Bernard M ; Vink, Hans ; VanTeeffelen, Jurgen W. G. E</creatorcontrib><description>1 Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht; and Departments of 2 Medical Physics and 3 Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Submitted December 18, 2008 ; accepted in final form November 23, 2009 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 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. adenosine; blood flow; coronary circulation; indicator-dilution Address for reprint requests and other correspondence: J. W. G. E. VanTeeffelen, Dept. of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht Univ., PO Box 616, 6200 MD Maastricht, The Netherlands (e-mail: j.vanteeffelen{at}FYS.unimaas.nl ).</description><identifier>ISSN: 0363-6135</identifier><identifier>EISSN: 1522-1539</identifier><identifier>DOI: 10.1152/ajpheart.01306.2008</identifier><identifier>PMID: 19940074</identifier><identifier>CODEN: AJPPDI</identifier><language>eng</language><publisher>United States: American Physiological Society</publisher><subject>Adenosine ; Adenosine - pharmacology ; Animals ; Blood Volume - physiology ; Cell Membrane - physiology ; Coronary vessels ; Coronary Vessels - drug effects ; Coronary Vessels - physiology ; Enzymes ; Erythrocytes ; Female ; Glycocalyx - drug effects ; Glycocalyx - physiology ; Goats ; Hyaluronoglucosaminidase - pharmacology ; Models, Animal ; Models, Biological ; Regional Blood Flow - physiology ; Studies ; Vasodilation - drug effects ; Vasodilator Agents - pharmacology</subject><ispartof>American journal of physiology. 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Heart and circulatory physiology</title><addtitle>Am J Physiol Heart Circ Physiol</addtitle><description>1 Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht; and Departments of 2 Medical Physics and 3 Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Submitted December 18, 2008 ; accepted in final form November 23, 2009 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 40%, which is of similar magnitude as additional changes in coronary blood volume during subsequent maximal vasodilation with adenosine. 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VanTeeffelen, Dept. of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht Univ., PO Box 616, 6200 MD Maastricht, The Netherlands (e-mail: j.vanteeffelen{at}FYS.unimaas.nl ).</description><subject>Adenosine</subject><subject>Adenosine - pharmacology</subject><subject>Animals</subject><subject>Blood Volume - physiology</subject><subject>Cell Membrane - physiology</subject><subject>Coronary vessels</subject><subject>Coronary Vessels - drug effects</subject><subject>Coronary Vessels - physiology</subject><subject>Enzymes</subject><subject>Erythrocytes</subject><subject>Female</subject><subject>Glycocalyx - drug effects</subject><subject>Glycocalyx - physiology</subject><subject>Goats</subject><subject>Hyaluronoglucosaminidase - pharmacology</subject><subject>Models, Animal</subject><subject>Models, Biological</subject><subject>Regional Blood Flow - physiology</subject><subject>Studies</subject><subject>Vasodilation - drug effects</subject><subject>Vasodilator Agents - pharmacology</subject><issn>0363-6135</issn><issn>1522-1539</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><recordid>eNpdkV1rFDEUhkNR7Nr6CwQJ3ng1az4mH3NZilqh4I29DtnMyW6W7GRMZlrn35t1txa8SQLvc15yeBB6T8maUsE-2_24A5unNaGcyDUjRF-gVU1YQwXvXqEV4ZI3knJxid6WsieECCX5G3RJu64lRLUrtNy4eQJspwmG2U4hDTh5vI2LS87G5Tfe2JwDZDzmNEKeAhQcBpfBlvpyKafB5gVvYko9fkxxPkDNexihHsMUl2PdP8zH9IQzFMiPcI1eexsLvDvfV-jh65eft3fN_Y9v329v7hvXcjk1XIne0lY76In2TPeWE-K1UlK3QnsidM-tqJEDblsPVgjet77rtJNSbQi_Qp9OvXWDXzOUyRxCcRCjHSDNxSjOJaVMHcmP_5H7NOehfs4w1glNFG8rxE-Qy6mUDN6MORzqcoYSc_Rinr2Yv17M0Uud-nCunjcH6F9mziIqsD4Bu7DdPYUMZtwtJaSYtstLI-u0YeZOVL9_AJPenn8</recordid><startdate>20100201</startdate><enddate>20100201</enddate><creator>Brands, Judith</creator><creator>Spaan, Jos A. 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Heart and circulatory physiology</jtitle><addtitle>Am J Physiol Heart Circ Physiol</addtitle><date>2010-02-01</date><risdate>2010</risdate><volume>298</volume><issue>2</issue><spage>H515</spage><epage>H523</epage><pages>H515-H523</pages><issn>0363-6135</issn><eissn>1522-1539</eissn><coden>AJPPDI</coden><abstract>1 Department of Physiology, Cardiovascular Research Institute Maastricht, Maastricht University, Maastricht; and Departments of 2 Medical Physics and 3 Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands Submitted December 18, 2008 ; accepted in final form November 23, 2009 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 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. adenosine; blood flow; coronary circulation; indicator-dilution Address for reprint requests and other correspondence: J. W. G. E. VanTeeffelen, Dept. of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht Univ., PO Box 616, 6200 MD Maastricht, The Netherlands (e-mail: j.vanteeffelen{at}FYS.unimaas.nl ).</abstract><cop>United States</cop><pub>American Physiological Society</pub><pmid>19940074</pmid><doi>10.1152/ajpheart.01306.2008</doi></addata></record>
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ispartof American journal of physiology. Heart and circulatory physiology, 2010-02, Vol.298 (2), p.H515-H523
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subjects Adenosine
Adenosine - pharmacology
Animals
Blood Volume - physiology
Cell Membrane - physiology
Coronary vessels
Coronary Vessels - drug effects
Coronary Vessels - physiology
Enzymes
Erythrocytes
Female
Glycocalyx - drug effects
Glycocalyx - physiology
Goats
Hyaluronoglucosaminidase - pharmacology
Models, Animal
Models, Biological
Regional Blood Flow - physiology
Studies
Vasodilation - drug effects
Vasodilator Agents - pharmacology
title Acute attenuation of glycocalyx barrier properties increases coronary blood volume independently of coronary flow reserve
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