P-selectin inhibition prevents early neutrophil activation but provides only modest protection against myocardial injury in dogs with ischemia and forty-eight hours reperfusion
Masazumi Arai, MDa,
Yoshihiro Masui, MDa,
Pascal Goldschmidt-Clermont, MDa,
Anthony DiPaula, BSa,
Cynthia Siu, PhDa,
Takeshi Kondo, MDa and
Lewis C. Becker, MD, FACCa
a Division of Cardiology, Department of Medicine, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
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Figure 1 In vitro PB1.3 binding to dog platelets stimulated by thrombin receptor–activating peptide (TRAP) or platelet-activating factor (PAF). Mean channel fluorescence increased in a concentration-dependent manner, indicating cross-reactivity of PB1.3 to dog P-selectin.
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Figure 2 Relation between infarct size and the severity of ischemia in control (open circles) and PB1.3 antibody (closed circles) groups. The regression line for PB1.3 was shifted significantly downward (p = 0.003 by analysis of covariance).
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Figure 3 Time course of CD18 expression on circulating polymorphonuclear neutrophils (PMNs). In the control group, CD18 expression increased significantly at 30 min after reperfusion, and returned to the baseline level by 2 h. However, treatment with PB1.3 prevented up-regulation of CD18 at 30 min after reperfusion. The curves were also significantly different after 1 h reperfusion by profile analysis.
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Figure 4 CD18 expression on circulating neutrophils at 30 min after reperfusion was correlated with the size of the area at risk in the control group (open circles, y = 58.8 + 1.6x, r = 0.83) but not in the group receiving PB1.3 (closed circles, y = 86.9 + 0.3x, r = 0.18). This suggests that the amount of neutrophil activation is dependent on the amount of ischemic–reperfused myocardium and that this activation can be prevented by PB1.3. LV = left ventricle.
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Figure 5 Regional myocardial function assessed by left ventriculography. Chord shortening was averaged in the anterior (infarct) and posterior (control) regions. Wall motion was markedly reduced in the infarct region during occlusion and recovered slightly after reperfusion (**p < 0.01 vs. baseline). However, there was no significant difference in regional wall motion between the two groups at any time point.
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