title: Acute vasomotor paralysis and potential downstream effects of paclitaxel from stents implanted for saphenous vein aorto-coronary bypass stenosis.
abstract: Implantation of bare metal stents (BMS) induces the release not only of particulate debris, but also of soluble vasoconstrictors which contribute to microvascular impairment. So this study aimed at addressing the potential attenuation of such vasoconstriction using paclitaxel eluting stents (PES). Using a distal protection/aspiration device, coronary arterial blood was retrieved before and during stent [n = 14 BMS, n = 14 PES, n = 3 sirolimus eluting stents (SES)] implantation in patients with saphenous vein aorto-coronary bypass stenosis and analyzed for plasma serotonin and thromboxane B(2) concentrations. The vasoconstriction of rat mesenteric arteries with intact (+E) and denuded (-E) endothelium in response to coronary arterial or aspirate plasma was quantified and normalized to that by potassium chloride (KCl(max) = 100%). Coronary arterial plasma before stent implantation induced a vasoconstriction of 30-43%, which was independent of endothelial integrity. Serotonin-release was 2.2 ± 0.5 μmol/l with BMS and 2.0 ± 0.4 μmol/l with PES, thromboxane B(2)-release was 26 ± 5 pg/ml with BMS and 22 ± 8 pg/ml with PES. BMS- and SES-aspirate plasma induced a vasoconstriction of 68 ± 18% (+E)/93 ± 14% (-E) and 81 ± 17% (+E)/124 ± 14% (-E), respectively. In contrast, PES-aspirate plasma induced only minor vasoconstriction of 8 ± 3% (+E)/12 ± 5% (-E). Addition of paclitaxel to BMS-aspirate plasma attenuated vasoconstriction. PES-aspirate induced microtubular condensation in immunofluorescence microscopy. Results indicate that aspirate from PES implantation attenuates vasoconstriction, possibly secondary to microtubular stabilization. Such acute downstream vascular paralysis could be beneficial in preventing a no-reflow phenomenon in patients undergoing stenting.
authors.affiliation: Institut für Pathophysiologie, Universitätsklinikum Essen, Hufelandstrasse 55, Essen, Germany.
authors.forename: Petra
authors.initials: P
authors.lastname: Kleinbongard
authors.forename: Dirk
authors.initials: D
authors.lastname: Böse
authors.forename: Thomas
authors.initials: T
authors.lastname: Konorza
authors.forename: Florian
authors.initials: F
authors.lastname: Steinhilber
authors.forename: Stefan
authors.initials: S
authors.lastname: Möhlenkamp
authors.forename: Holger
authors.initials: H
authors.lastname: Eggebrecht
authors.forename: Theodor
authors.initials: T
authors.lastname: Baars
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: Raimund
authors.initials: R
authors.lastname: Erbel
authors.forename: Gerd
authors.initials: G
authors.lastname: Heusch
mesh_terms: D000368:Aged; D000818:Animals; D001026:Coronary Artery Bypass / Q000009:adverse effects*; D023921:Coronary Stenosis / Q000628:therapy*; D054855:Drug-Eluting Stents; D005260:Female; D006801:Humans; D008297:Male; D017239:Paclitaxel / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D012501:Saphenous Vein / Q000637:transplantation*; D012701:Serotonin / Q000097:blood; D013929:Thromboxane B2 / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D012701:Serotonin; D013929:Thromboxane B2; D017239:Paclitaxel