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Endothelium-Dependent Vasoconstriction in Isolated Vessel Grafts: A Novel Mechanism of Vasospasm?  Markus Hoenicka, PhD, Andreas Keyser, MD, Leopold Rupprecht,

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Presentation on theme: "Endothelium-Dependent Vasoconstriction in Isolated Vessel Grafts: A Novel Mechanism of Vasospasm?  Markus Hoenicka, PhD, Andreas Keyser, MD, Leopold Rupprecht,"— Presentation transcript:

1 Endothelium-Dependent Vasoconstriction in Isolated Vessel Grafts: A Novel Mechanism of Vasospasm? 
Markus Hoenicka, PhD, Andreas Keyser, MD, Leopold Rupprecht, MD, Thomas Puehler, MD, Stephan Hirt, MD, Christof Schmid, MD  The Annals of Thoracic Surgery  Volume 92, Issue 4, Pages (October 2011) DOI: /j.athoracsur Copyright © 2011 The Society of Thoracic Surgeons Terms and Conditions

2 Fig 1 YC-1–induced constriction of rings of human saphenous vein and human radial artery. (A) Representative organ-bath tracing showing the effects on human saphenous vein of 3 μmol/L YC-1 (upper tracing) and dimethylsulfoxide solvent control (lower tracing). Arrows indicate time of administration of test compound; w = washing; NE = serial norepinephrine concentrations from 1 × 10−11 mol/L to 3 × 10−6 mol/L; SNP = sodium nitroprusside at 50 μmol/L added to rings of both human saphenous vein and human radial artery. (B) Effects on rings of human radial artery of same conditions as in A. Note the spontaneous oscillations of constriction and relaxation in this example. (C) Distribution in patient pool of maximum tension induced by 3 μmol/L YC-1. Constrictions induced by both YC-1 and norepinephrine were determined in specimens of human saphenous vein from 134 patients. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2011 The Society of Thoracic Surgeons Terms and Conditions

3 Fig 2 Organ-bath tracings of YC-1–induced relaxations of human saphenous vein preconstricted with norepinephrine. Arrow indicates addition of 1 × 10−8 mol/L sodium nitroprusside. Vertical marks at bottom of figure indicate sodium nitroprusside dose–response curve from 1 × 10−10 mol/L to 3 × 10−5 mol/L. Crosses indicate YC-1 dose–response curve from 1 × 10−8 mol/L to 3 × 10−5 mol/L. Tracings are representative of 5 independent experiments. The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2011 The Society of Thoracic Surgeons Terms and Conditions

4 Fig 3 Differentiation of vasorelaxant and vasoconstrictive effects of YC-1. Specimens of human saphenous vein were constricted with increasing doses of YC-1 in the absence (filled circles) or presence (open circles) of the soluble guanylyl cyclase inhibitor 1H-(1,2,4)axadiazole(4,3-a)quinoxalin-1-one (ODQ; 10 mmol/L). *Significantly different value for absence and presence of ODQ (p = 0.012, analysis of variance [ANOVA], n = 6). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2011 The Society of Thoracic Surgeons Terms and Conditions

5 Fig 4 Dependence of YC-1-induced contractions on endothelium. (A) and (B) Representative hematoxylin-and-eosin-stained cross sections of native and endothelium-denuded human saphenous vein, respectively. (Original magnification in panels A and B, × 10.) (C) YC-1 dose-response curves of native (filled circles) and endothelium-denuded human saphenous vein (open circles). Curves are significantly different (p < 0.001, Analysis of variance [ANOVA], n = 8). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2011 The Society of Thoracic Surgeons Terms and Conditions

6 Fig 5 Effects of calcium channel, endothelin receptor, endothelin converting enzyme, and thromboxane A2/prostaglandin H2 receptor antagonists on YC-1–induced constriction of human saphenous vein. Cumulative YC-1 dose –response curves (control, filled circles) were constructed after administering nifedipine (1 μmol/L, open circles), bosentan (10 μmol/L, filled triangles), BQ-123 (3 μmol/L, open triangles), BQ-788 (0.5 μmol/L, filled squares), phosphoramidon (10μmol/L, open squares), and SQ29,548 (0.3 μmol/L, filled diamonds). *Significantly different value from control (p < 0.001, analysis of variance[ANOVA], n = 6 or 7). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2011 The Society of Thoracic Surgeons Terms and Conditions

7 Fig 6 Endothelin-1 release from rings of human saphenous vein in organ baths after exposure to YC-1 for 60 minutes. The release of endothelin-1 increased significantly with an increasing YC-1 concentration (p = 0.032, analysis of variance [ANOVA], n = 7). The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2011 The Society of Thoracic Surgeons Terms and Conditions

8 Fig 7 Putative mechanism of YC-1–induced vasoconstriction. (AA = arachidonic acid; COX = cyclooxygenase; EC = endothelial cell; ECE = endothelin-converting enzyme; ET-1 = endothelin-1; MLCK = myosin light-chain kinase; PG = prostaglandin; SMC = smooth-muscle cell.) The Annals of Thoracic Surgery  , DOI: ( /j.athoracsur ) Copyright © 2011 The Society of Thoracic Surgeons Terms and Conditions

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