title: Vasoconstrictor potential of coronary aspirate from patients undergoing stenting of saphenous vein aortocoronary bypass grafts and its pharmacological attenuation.
abstract: BACKGROUND
  Stent implantation into atherosclerotic plaques releases, apart from particulate debris, soluble substances that contribute to impaired microvascular perfusion.
  
  
  OBJECTIVE
  To quantify the release of vasoconstrictors and to determine the efficacy of coronary dilators to attenuate their action.
  
  
  RESULTS
  Using a distal protection/aspiration device, coronary arterial blood was retrieved before and during stenting in 22 patients with severe saphenous vein aorto-coronary bypass stenoses. The release of catecholamines, endothelin, serotonin, thromboxane B(2), and tumor necrosis factor (TNF)α was measured. The response of rat mesenteric arteries with intact (+E) and denuded (-E) endothelium to aspirate plasma was normalized to that by KCl. Responses to selective receptor blockade, adenosine, nitroprusside, and verapamil against the aspirate-induced constriction were determined. The coronary arterial plasma withdrawn before stenting induced 21±5% and the aspirate plasma after stenting induced 95±8% of maximum KCl-induced vasoconstriction. Serotonin, thromboxane B(2), and TNFα release into aspirate plasma increased by 1.9±0.2 μmol/L, 25.6±3.1 pg/mL, and 19.7±6.1 pg/mL, respectively, during stenting. The aspirate-induced vasoconstriction was largely antagonized by selective serotonin receptor blockade, with little further antagonism by additional thromboxane receptor blockade. TNFα did not induce constriction per se but potentiated the constriction with serotonin and the thromboxane-analog U-46619 in arteries +E. The concentrations to induce half-maximal vasodilation were comparable for nitroprusside (+E, 3.3×10(-8); -E, 1.9×10(-8) mol/L) and verapamil (+E, 8.3×10(-8); -E, 7.8×10(-8) mol/L), and the vasoconstriction was eventually eliminated. The vasodilator response to adenosine was dependent on functional endothelium and weaker.
  
  
  CONCLUSIONS
  Serotonin is the main coronary vasoconstrictor after stenting, and thromboxane and TNFα somewhat potentiate the serotonin response. Nitroprusside and verapamil are more potent than adenosine to attenuate the aspirate plasma-induced vasoconstriction, and they are not dependent on functional endothelium.
authors.affiliation: FRCP, Institut für Pathophysiologie, Universitätsklinikum Essen, Hufelandstr. 55, 45122 Essen, Germany. gerd.heusch@uk-essen.de.
authors.forename: Petra
authors.initials: P
authors.lastname: Kleinbongard
authors.forename: Dirk
authors.initials: D
authors.lastname: Böse
authors.forename: Theodor
authors.initials: T
authors.lastname: Baars
authors.forename: Stefan
authors.initials: S
authors.lastname: Möhlenkamp
authors.forename: Thomas
authors.initials: T
authors.lastname: Konorza
authors.forename: Sandra
authors.initials: S
authors.lastname: Schöner
authors.forename: Miriam
authors.initials: M
authors.lastname: Elter-Schulz
authors.forename: Holger
authors.initials: H
authors.lastname: Eggebrecht
authors.forename: Hubertus
authors.initials: H
authors.lastname: Degen
authors.forename: Michael
authors.initials: M
authors.lastname: Haude
authors.forename: Bodo
authors.initials: B
authors.lastname: Levkau
authors.forename: Rainer
authors.initials: R
authors.lastname: Schulz
authors.forename: Raimund
authors.initials: R
authors.lastname: Erbel
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000368:Aged; D000818:Animals; D001026:Coronary Artery Bypass; D016232:Endothelins / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000503:physiopathology; D008875:Middle Aged; D023421:Models, Animal; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011917:Rats, Inbred Lew; D012501:Saphenous Vein / Q000637:transplantation*; D012701:Serotonin / Q000494:pharmacology; D015607:Stents; D013929:Thromboxane B2 / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
chemical_list: D016232:Endothelins; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D009599:Nitroprusside; D012701:Serotonin; D013929:Thromboxane B2; D014700:Verapamil; D000241:Adenosine