Effect of aprotinin on vascular reactivity of coronary bypass grafts.
OBJECTIVE
Aprotinin reduces postoperative bleeding and the need for transfusion after cardiopulmonary bypass. The current clinical concern about aprotinin is that it may increase the incidence of postoperative graft thrombosis and thromboembolic phenomena. The fact that the mechanism of action of aprotinin is not completely elucidated and that its effects on the vascular reactivity of bypass conduits are unknown raise doubts regarding its safety. In an attempt to clarify these issues we investigated the vascular reactivity of the human saphenous vein and internal thoracic artery to a range of vasoconstrictor agents in the presence or absence of aprotinin.


METHODS
Human saphenous vein was obtained from 24 patients and internal thoracic artery from 7 patients undergoing coronary artery bypass. Vessels were set up in organ baths to record changes in vessel wall tension.


RESULTS
Endothelium-dependent relaxations to acetylcholine in saphenous vein rings were unaffected after aprotinin treatment. Contractions to the thromboxane analog U46619 were significantly attenuated after aprotinin treatment in the saphenous vein. Maximum responses were reduced from control values of 88 +/- 7.5 mN to 49.3 +/- 4.8 mN with 1 mumol/L doses of aprotinin (p < 0.05) and 36.6 +/- 4.8 mN with 10 mumol/L doses of 5-hyroxytryptamine or noradrenaline after aprotinin incubations. Furthermore, contractions to U46619 in the internal thoracic artery were unaffected by aprotinin.


CONCLUSIONS
Our data show that there is a preservation of endothelium-dependent responses to acetylcholine and a reduced U46619 vasoconstrictor action on the saphenous vein after aprotinin treatment. Thus the direct effect of aprotinin on the vessel wall could counteract the potential effect of its prothrombotic action on graft patency.
Allen
S
S
Department of Cardiothoracic Surgery, Harefield Hospital, Middlesex, United Kingdom.
Anastasiou
N
N
Royston
D
D
Paniagua
R
R
Yacoub
M
M
D000109:Acetylcholine / Q000502:physiology; D007611:Aprotinin / Q000494:pharmacology*; D001026:Coronary Artery Bypass; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D006490:Hemostatics / Q000494:pharmacology*; D006801:Humans; D012501:Saphenous Vein / Q000502:physiology; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013895:Thoracic Arteries / Q000502:physiology; D013928:Thromboxane A2 / Q000031:analogs & derivatives; D014661:Vasoconstriction / Q000187:drug effects*
D006490:Hemostatics; D015842:Serine Proteinase Inhibitors; D013928:Thromboxane A2; D007611:Aprotinin; D000109:Acetylcholine