Effect of aspirin on coronary collateral blood flow.
BACKGROUND
Although aspirin exerts beneficial antiplatelet activity in patients with coronary artery disease, cyclooxygenase blockade produced by aspirin causes a potentially deleterious effect by interrupting endothelial production of prostacyclin. Collateral vessels that develop in response to coronary occlusion display prominent endothelial cell proliferation and undergo vasoconstriction in response to indomethacin. This study was performed to test the hypothesis that cyclooxygenase blockade with aspirin would cause constriction of coronary collateral vessels and that such vasoconstriction would be reversed with nitroglycerin.


RESULTS
Collateral vessel growth was induced by embolic occlusion of the left anterior descending coronary artery in dogs. Four to 6 months later, coronary collateral flow was measured as retrograde flow from the cannulated collateral-dependent artery. Aspirin (1 mg/kg i.v.) caused 70 +/- 8% blockade of the increase in coronary blood flow produced by intra-arterial arachidonic acid and decreased retrograde flow from 37 +/- 7 to 28 +/- 7 ml/min (p < 0.03). Increasing the dose of aspirin to 15 mg/kg i.v. caused 91 +/- 3% blockade of the response to arachidonic acid and further decreased retrograde flow to 21 +/- 4 ml/min (p < 0.01). After aspirin administration, nitroglycerin (150 micrograms/min i.c.) reversed the collateral constriction and increased retrograde flow to 37 +/- 10 ml/min (p < 0.01).


CONCLUSIONS
These data suggest that products of cyclooxygenase metabolism cause tonic vasodilation of well-developed coronary collateral vessels. Blockade of cyclooxygenase with even low-dose aspirin caused collateral vessel constriction with a decrease in collateral blood flow. However, nitroglycerin was able to fully reverse aspirin-induced collateral vasoconstriction and restore flow to the control level.
Altman
J D
JD
Department of Medicine, University of Minnesota Medical School, Minneapolis 55455.
Dulas
D
D
Pavek
T
T
Bache
R J
RJ
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D003097:Collateral Circulation / Q000187:drug effects*; D003326:Coronary Circulation / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D016718:Arachidonic Acid; D005996:Nitroglycerin; D001241:Aspirin