Thrombosis resulting from blood platelet aggregation via glycoprotein (GP) IIb/IIIa receptor activation triggers the local release of vasoactive substances. Therefore, inhibition of these receptors could affect coronary vasoactive function during thrombotic coronary arteriostenosis. Twenty pigs were instrumented with an aortic catheter and with hydraulic occluders and flow probes on both the left anterior descending (LAD) and the left circumflex (LCx) coronary arteries. One of these 2 coronary

more »

... rteries was repeatedly injured by external clamping for 15-second periods at 30-minute intervals while the pigs were given either a GP IIb/IIIa receptor inhibitor (L-739,758) (nϭ5), heparin (nϭ5), aspirin (nϭ3), or saline (nϭ7). There were no baseline differences between the 4 groups in mean arterial pressure, resting coronary blood flow (CBF), or reactive hyperemic response (RHR), which was induced by brief coronary artery occlusion and expressed as flow debt repayment. After multiple injuries, resting CBF had decreased by 95Ϯ2% (ie, nearly complete coronary artery occlusion) at 15Ϯ4 minutes in the control group, whereas in the heparin-, aspirin-, and GP IIb/IIIa inhibitor-treated groups, resting CBF had decreased by only 21Ϯ7% at 18Ϯ3 minutes, 15Ϯ3% at 18Ϯ5 minutes, and 15Ϯ7% at 21Ϯ4 minutes, respectively, suggesting that heparin, aspirin, and the GP IIb/IIIa inhibitor each prevented injury-induced coronary artery occlusion. After the initial injury, the RHR was progressively reduced in the control and heparin-and aspirin-treated groups but not in the GP IIb/IIIa inhibitor-treated group. At a comparable level of resting CBF (Ϸ15% below baseline), the RHR was reduced more in the control (Ϫ56Ϯ9%), heparin-treated (Ϫ49Ϯ9%), and aspirin-treated (Ϫ61Ϯ12) groups (PϽ0.05) than in the GP IIb/IIIa inhibitor-treated group (Ϫ26Ϯ6%). When the resting CBF had decreased by Ϸ35%, the RHR still was reduced significantly more (PϽ0.01) in the heparin-treated group (Ϫ64Ϯ9%) than in the GP IIb/IIIa inhibitor-treated group (Ϫ21Ϯ6%). In a separate group of control pigs (nϭ4) subjected to 2 injuries, coronary perfusion pressure distal to the injury site was reduced by 14Ϯ1 mm Hg from the arterial pressure, and the RHR was 20Ϯ6%. When the distal coronary perfusion pressure was reduced similarly (Ϫ14Ϯ1 mm Hg) in a separate group of GP IIb/IIIa inhibitor-treated pigs (nϭ4) by 2 injuries and the use of a hydraulic occluder, the RHR was 130Ϯ16% (PϽ0.01 versus control). Our data demonstrate for the first time that a platelet GP IIb/IIIa receptor inhibitor can preserve the distal coronary vasodilatory response during progressive coronary arteriostenosis. (Arterioscler Thromb Vasc Biol. 2000;20:2309-2315.) Key Words: coronary reactive hyperemia Ⅲ coronary reserve Ⅲ heparin Ⅲ aspirin Ⅲ coronary injury Ⅲ glycoprotein IIb/IIIa