Specific coronary drug-eluting stents interfere with distal microvascular function after single stent implantation in pigs.
OBJECTIVE
The aim of this study was to compare the effects of single drug-eluting stents (DES) on porcine coronary function distal to the stent in vivo and in vitro.


BACKGROUND
The mechanism of endothelial dysfunction occurring in human coronary conduit arteries up to 9 months after DES implantation is unknown.


METHODS
A sirolimus-eluting stent (SES), paclitaxel-eluting stent (PES), and a bare-metal stent (BMS) were implanted in the 3 coronary arteries of 11 pigs. After 5 weeks, in vivo responses in distal coronary flow to different doses of bradykinin (BK) and nitrates were measured. In vitro, vasodilation to BK and nitrates, as well as vasoconstriction to endothelin (ET)-1 were assessed in both distal coronary conduit and small arteries. In addition, contributions of nitric oxide (NO) and endothelium-derived hyperpolarizing factors (EDHFs) and cyclic guanosine monophosphate (cGMP) responses to BK-stimulation were determined in vitro.


RESULTS
Both DES did not alter in vivo distal vasomotion. In vitro distal conduit and small arterial responses to BK were also unaltered; DES did not alter the BK-induced increase in cGMP. However, after NO synthase blockade, PES showed a reduced BK-response in distal small arteries as compared with BMS and SES (p < 0.05). The ET-1-induced vasoconstriction and vascular smooth muscle cell function were unaltered.


CONCLUSIONS
In this study of single stenting in healthy porcine coronaries for 5 weeks, SES did not affect distal coronary vascular function, whereas PES altered distal endothelial function of small arteries under conditions of reduced NO bioavailability. Therefore, specifically the EDHF component of microvascular function seems affected by PES.
van den Heuvel
Mieke
M
Department of Cardiology, Thoraxcenter, Erasmus University Medical Center, Rotterdam, the Netherlands.
Sorop
Oana
O
Batenburg
Wendy W
WW
Bakker
Charlotte L
CL
de Vries
René
R
Koopmans
Sietse Jan
SJ
van Beusekom
Heleen M M
HM
Duncker
Dirk J
DJ
Danser
A H Jan
AH
van der Giessen
Willem J
WJ
D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects / Q000295:instrumentation*; D000818:Animals; D001685:Biological Factors / Q000378:metabolism; D002317:Cardiovascular Agents / Q000008:administration & dosage; D017023:Coronary Angiography; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D054855:Drug-Eluting Stents; D015150:Echocardiography, Doppler; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D008297:Male; D008670:Metals; D008833:Microcirculation / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D017239:Paclitaxel / Q000008:administration & dosage; D011474:Prosthesis Design; D020123:Sirolimus / Q000008:administration & dosage; D015607:Stents; D013552:Swine; D013997:Time Factors; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D001685:Biological Factors; D002317:Cardiovascular Agents; D008670:Metals; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D006152:Cyclic GMP; D017239:Paclitaxel; D020123:Sirolimus