Reduction of Myocardial Infarct Size After Ischemia and Reperfusion by the Glycosaminoglycan Pentosan Polysulfate

Abstract

Activation of the complement system contributes to the tissue destruction associated with myocardial ischemia/reperfusion. Pentosan polysulfate (PPS), a negatively charged sulfated glycosaminoglycan (GAG) and an effective inhibitor of complement activation, was studied for its potential to decrease infarct size in an experimental model of myocardial ischemia/reperfusion injury. Open-chest rabbits were subjected to 30-min occlusion of the left coronary artery followed by 5 h of reperfusion. Vehicle (saline) or PPS (30 mg/kg/h) was administered intravenously immediately before the onset of reperfusion and every hour during the reperfusion period. Treatment with PPS significantly (p < 0.05) reduced infarct size as compared with vehicle-treated animals (27.5+/-2.9% vs. 13.34+/-2.6%). Analysis of tissue demonstrated decreased deposition of membrane-attack complex and neutrophil accumulation in the area at risk. The results indicate that, like heparin and related GAGs, PPS possesses the ability to decrease infarct size after an acute period of myocardial ischemia and reperfusion. The observations are consistent with the suggestion that PPS may mediate its cytoprotective effect through modulation of the complement cascade.

Sulodexide Attenuates Myocardial Ischemia/Reperfusion Injury and the Deposition of C-Reactive Protein in Areas of Infarction without Affecting Hemostasis

“…administration of KRX-101 results in a decrease in myocardial infarct size in a model of in vivo regional ischemia/ reperfusion. The results are in accordance with previous studies in which it was found that other glycosaminoglycans have the ability to reduce infarct size in vivo Black et al, 1995;Gralinski et al, 1996;Kilgore et al, 1998;Tanhehco et al, 1999).…”

“…Glycosaminoglycans (GAGs) are a group of compounds reported to be of benefit to the ischemic myocardium by preserving contractile function and reducing tissue injury Black et al, 1995;Gralinski et al, 1996;Kilgore et al, 1998;Tanhehco et al, 1999). In addition, selective GAGs are known to possess anticomplement activity in addition to their classical roles as anticoagulants.…”

C-Reactive-Protein-Associated Increase in Myocardial Infarct Size After Ischemia/Reperfusion

“…Blood samples were anticoagulated with heparin (5 U/ml final concentration). This concentration of heparin does not affect activation of the complement cascade (Tanhehco et al, 1999). Plasma samples were prepared by low-speed centrifugation and frozen at Ϫ70°C until assayed.…”

Sulodexide: A Renewed Interest in This Glycosaminoglycan

“…Various GAGs have been reported by our laboratory to be of benefit to the ischemic myocardium by preserving contractile function and reducing tissue injury (6,29,35,46,70). In addition, selective GAGs are known to possess anti-complement activity in addition to their classical roles as anticoagulants.…”