Vasomotor response to different endothelium-dependent vasodilators in an animal model.
OBJECTIVE
Incomplete re-endothelialization of stents can be revealed as paradoxical vasoconstriction with endothelium-dependent vasodilators. As no consensus exists about the best method or agent, our objective is to analyze the response to different drugs in a coronary swine model.


METHODS
Twenty-seven stents were implanted in 9 domestic swine. The vessel diameter of proximal and distal segments (≥5 mm) was assessed immediately post implantation. Different endothelium-dependent vasodilators were used: intracoronary (IC) acetylcholine, 20 μg (A2) and 40 μg (A4), IC serotonin (S), 100 μg, and isoproterenol (I), intravenous infusion. The results are presented as constriction (%) compared with maximal vasodilation with IC nitroglycerin (N, 200 μg).


RESULTS
In 10 vessels (37%), A4 provoked an occlusive spasm. Acetylcholine induced a higher degree of vasoconstriction (A4, 42 ± 39%; A2, 16 ± 14%) than the rest of the agonists (S, 6 ± 12%; I, 6 ± 11%; P<.01). The constriction rate was not related to the induced hemodynamic changes.


CONCLUSIONS
After focal endothelial denudation in a coronary swine model, the constriction rate induced by different endothelium-dependent vasodilators is highly variable. The highest value is observed after IC acetylcholine bolus. The constriction rate does not correlate with the observed hemodynamic changes.
Fundación Investigacion Sanitaria en León – HemoLeon and Institute of Biomedicine (IBIOMED), León, Spain. aperez@secardiologia.es
Armando
A
Pérez de Prado
Carlos
C
Cuellas
Alejandro
A
Diego
Jose M
JM
Gonzalo-Orden
Claudia
C
Pérez-Martínez
Marta
M
Regueiro
Antonio
A
de Miguel
Jose M
JM
Ajenjo
Beatriz
B
Martínez-Fernández
Jose R
JR
Altonaga
Felipe
F
Fernández-Vázquez
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D023421:Models, Animal; D005996:Nitroglycerin / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D015607:Stents; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology*; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology*
D014665:Vasodilator Agents; D012701:Serotonin; D005996:Nitroglycerin; D007545:Isoproterenol; D000109:Acetylcholine