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Platelet GPIIb/IIIa receptor blockade reduces infarct size in a canine model of ischemia-reperfusion

John G. Kingma, Jr., PhD, FACC^*, Sylvain Plante, MD, FACC^* and Peter Bogaty, MD^*

^* Department of Medicine, Faculty of Medicine, Laval University, Sainte-Foy, Quebec, Canada
Quebec Heart Institute, Laval Hospital, Sainte-Foy, Quebec, Canada

View larger version (32K): [in a new window]   Figure 1 Effects of MK-0852 on collagen-induced platelet glycoprotein IIb/IIIa receptor activation. Platelet rich plasma from venous blood (i.e., from the ischemic zone) was prepared as described in the Methods section. Some spontaneous platelet aggregation was observed before the addition of collagen (5 µg/mL) in vehicle treated dogs (A); this did not occur after administration of MK-0852 (C). Collagen induced significant platelet aggregation in vehicle treated dogs (B), but this reaction was significantly blunted with MK-0852 treatment (D). MK-0852 = N-acetyl-cys-asn-(5,5-dimethyl-4-thiazolidine-carbonyl)-4-amino-methyl-phe-gly-asp-cys, monoacetate.

View larger version (14K): [in a new window]   Figure 2 Changes in rate-pressure product during the ischemia-reperfusion protocol. Controls (i.e., heparin; open circles), MK-0852 plus heparin (open squares), MK-0852 (open triangles); the same symbols are used to identify each treatment group in all figures. I = ischemia; R = reperfusion. Data are means ± standard error of the mean.

View larger version (19K): [in a new window]   Figure 3 Systolic segment shortening (as % of baseline value) in the ischemic-reperfused myocardium during the experimental protocol (left panel); data for the nonischemic myocardium is also shown (right panel). Controls (i.e., heparin; open circles); MK-0852 plus HEP (open squares); MK-0852 (open triangles). Data are means ± standard error of the mean.

View larger version (22K): [in a new window]   Figure 4 Blood flow across the left ventricular wall from inner (End) to outer (Epi) layers at baseline, 30 min coronary occlusion and at 180 min coronary reperfusion in ischemic (upper panel) and nonischemic (lower panel) regions. Controls (open circles); MK plus HEP (open squares); MK (open triangles). Data are means ± standard error of the mean.

View larger version (16K): [in a new window]   Figure 5 Infarct size normalized to risk zone (left panel) and risk area as percent of the left ventricle (right panel) for each treatment group; data (mean ± standard error of the mean) for individual hearts (open circles) and mean values (closed squares) are shown. HEP = heparin; MK = MK-0852.

View larger version (20K): [in a new window]   Figure 6 Effect of MK-0852 on infarct size (% risk area) in dogs treated with MK-0852 plus HEP (open square; p < 0.05 vs. CON) or MK-0852 (open triangle; p < 0.05 vs. CON). Coronary collateral blood flow (mL/min/g) at 30-min coronary occlusion is also indicated. MK = MK-0852.