Administration of rsPSGL.Ig significantly reduced myocardial necrosis compared to a mutant form (16% vs. 42% of area-at-risk, P<0.01) in a feline model of ischemia-reperfusion injury.
Does recombinant soluble P-selectin glycoprotein ligand-1 reduce myocardial necrosis in cats subjected to myocardial ischemia-reperfusion injury?
Recombinant soluble PSGL-1 reduces myocardial reperfusion injury and preserves vascular endothelial function in a feline model by reducing neutrophil-endothelial cell interactions.
Absolute Event Rate: 16% vs 42%
p-value: p=<0.01
OBJECTIVE: Neutrophils (PMNs) contribute importantly to the tissue injury associated with ischemia and subsequent reperfusion of a vascular bed. The effects of a recombinant soluble human form of P-selectin glycoprotein ligand-1 (rsPSGL.Ig) on PMN-endothelial cell interactions were investigated in a well established model of feline myocardial-ischemia reperfusion injury. METHODS: Cats were subjected to 90 min of myocardial ischemia followed by 270 min of reperfusion. RESULTS: Administration of rsPSGL.Ig (1 mg/kg) just prior to reperfusion resulted in a significant reduction in myocardial necrosis compared to that in cats administered a low affinity mutant form of rsPSGL.Ig (1 mg/kg) (16 +/- 3 vs. 42 +/- 7% of area-at-risk, P < 0.01). Cardioprotective effects were confirmed by significant (P < 0.05) reductions in plasma creatine kinase activity in cats treated with rsPSGL.Ig. Inhibition of PMN-endothelial cell interactions was evidenced by a significant attenuation in cardiac myeloperoxidase activity (P < 0.01) and reduced PMN adherence to ischemic-reperfused coronary endothelium (P < 0.001). In addition, rsPSGL.Ig treatment significantly (P < 0.01) preserved endothelium-dependent vasorelaxation in ischemic-reperfused coronary arteries. CONCLUSION: These results demonstrate that the administration of a recombinant soluble PSGL-1 reduces myocardial reperfusion injury and preserves vascular endothelial function, which is largely the result of reduced PMN-endothelial cell interactions.
Reid Hayward (Sex,) conduziu uma pesquisa sobre lesão por reperfusão isquêmica miocárdica. A forma recombinant solúvel do ligante-1 da glicoproteína P-selectin humana (rsPSGL.Ig) vs. a forma mutante de baixa afinidade do rsPSGL.Ig (1 mg/kg) foi avaliada na necrose miocárdica (% da área em risco) (p=<0.01). A administração de rsPSGL.Ig reduziu significativamente a necrose miocárdica em comparação com a forma mutante (16% vs. 42% da área em risco, P<0.01) em um modelo felino de lesão por isquemia-reperfusão.
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