Reduction of myocardial infarct size after ischemia and reperfusion by the glycosaminoglycan pentosan polysulfate.
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.
Tanhehco
E J
EJ
Department of Pharmacology, University of Michigan Medical School, Ann Arbor 48109-0632, USA.
Kilgore
K S
KS
Naylor
K B
KB
Park
J L
JL
Booth
E A
EA
Lucchesi
B R
BR
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001792:Blood Platelets / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002633:Chemotaxis / Q000187:drug effects*; D003169:Complement Inactivator Proteins / Q000494:pharmacology; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D003331:Coronary Vessels / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects; D006025:Glycosaminoglycans / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008026:Ligation; D009203:Myocardial Infarction / Q000473:pathology*; D009504:Neutrophils / Q000502:physiology; D010426:Pentosan Sulfuric Polyester / Q000627:therapeutic use*; D011817:Rabbits; D015427:Reperfusion Injury / Q000188:drug therapy*; D012756:Sheep
D000906:Antibodies; D003169:Complement Inactivator Proteins; D015938:Complement Membrane Attack Complex; D004791:Enzyme Inhibitors; D006025:Glycosaminoglycans; D010426:Pentosan Sulfuric Polyester