Circulation, Vol 62, 1221-1227, Copyright © 1980 by American Heart Association
NL Capurro, LC Lipson, RO Bonow, RE Goldstein, NR Shulman and SE Epstein
Aspirin, as an inhibitor of platelet aggregation, may be of benefit in
ischemic heart disease. However, aspirin blocks not only platelet
aggregation but also synthesis of prostacyclin, a vasodilator and platelet
deaggregator. The relative sensitivity of prostaglandin- mediated coronary
vasodilatation and platelet aggregation to inhibition by aspirin remains
uncertain. We therefore investigated the relative dose-response
relationship of aspirin on arachidonic acid-induced increments in coronary
blood flow and on ADP-induced aggregation of platelets. In 11 open-chest
dogs, intracoronary arachidonic acid, 0.1- 3.0 mg, produced dose-related
increases in coronary blood flow that were inhibited progressively by i.v.
aspirin over the dose range 0.3- 3.0 mg/kg. Aspirin at 3 mg/kg almost
completely obliterated the response to 3 mg of arachidonic acid. Similarly,
aspirin doses of 0.3- 3.0 mg/kg progressively raised the minimal
concentration of ADP necessary for platelet aggregation. The threshold
concentration of ADP that produced aggregation of platelets from 10 control
dogs ranged from 2.3 x 10(-6) M to 1.2 x 10(-5) M. Aspirin at 3 mg/kg
completely inhibited aggregation of platelets from 11 of 12 dogs, even with
ADP at 2.3 x 10(-4) M concentration, the maximum tested. Aspirin at 0.1
mg/kg failed to inhibit either ADP-induced platelet aggregation or
arachidonic acid-induced increments in coronary blood flow. Thus, the two
test systems showed similar sensitivity to inhibition by aspirin with
respect to threshold dose and maximal effect. These results show that very
low doses of aspirin inhibit arachidonic acid-induced coronary
vasodilatation and that aspirin at low doses does not appear to selectively
inhibit platelet activity relative to coronary vasodilatation.
ARTICLES
Relative effects of aspirin on platelet aggregation and prostaglandin- mediated coronary vasodilatation in the dog
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