title: The low molecular weight heparin, enoxaparin, limits infarct size at reperfusion in the dog.
abstract: OBJECTIVE
  Heparin (HEP) is used in the post-thrombolytic state to prevent vessel reocclusion, thereby aiding myocardial salvage. Side effects limit its benefits, but besides anticoagulant activity HEP has diffuse actions that may be potentially beneficial to jeopardized reperfused myocardium. This study compares the effect of therapeutic doses of HEP and enoxaparin (ENOX), a low molecular weight heparin, and to streptokinase (SK), on infarct size.
  
  
  METHODS
  The left anterior descending coronary artery was occluded in dogs for 90 min, followed by 6 h of reperfusion with a residual critical stenosis in place. Five min before reperfusion, HEP (2800 IU) was injected i.v., and perfused at 500 IU/h until sacrifice in group 2, while groups 3 and 4 received ENOX (2128 anti-Xa IU i.v.) followed by 380 anti-Xa IU/h. Group 4 was also given 500,000 IU SK over 30 min before reperfusion beginning at 55 min of occlusion (ENOX + SK), while group 5 received only SK. Controls (CON, group 1) received saline. P-selectin mediated platelet-neutrophil rosettes formation was also tested in vitro in the presence of HEP and ENOX.
  
  
  RESULTS
  The area at risk delimited by dye perfusion was statistically similar among groups. Covariance analysis between infarct size (% of area at risk) delimited with triphenyltetrazolium and collateral flow measured with radioactive microspheres confirmed that groups given ENOX (21.6 +/- 5.5%) and ENOX + SK (24.9 +/- 3.9%) developed smaller infarcts (P < 0.05) than CON (48.1 +/- 4.5%), as opposed to HEP (32.2 +/- 3.6%) and SK (46.8 +/- 3.4%) groups. 111In-platelet counts in the infarct were reduced significantly by 64% in the ENOX group as compared to CON, and to a lesser extent (42%, n.s.) in the ENOX + SK group, but were not reduced by HEP and SK treatments. Neutrophil accumulation in the infarcts was decreased significantly and by more than 75% in the ENOX and ENOX + SK groups versus CON, but not in the HEP and SK groups. Also, only ENOX (10-100 micrograms/ml) significantly inhibited platelet-neutrophil rosettes formation in a plasmatic milieu.
  
  
  CONCLUSIONS
  The ENOX treatment, as opposed to that of HEP, reduces myocardial platelet and neutrophil accumulations, and limits infarct size when given just before and during reperfusion. The benefits of ENOX on infarct size were not modified by SK, and may be related, at least in part, to an interaction with P-selectin-mediated cell adhesion.
authors.affiliation: Laboratory of Experimental Pathology, Montreal Heart Institute, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Libersan
authors.forename: A
authors.initials: A
authors.lastname: Khalil
authors.forename: P
authors.initials: P
authors.lastname: Dagenais
authors.forename: E
authors.initials: E
authors.lastname: Quan
authors.forename: F
authors.initials: F
authors.lastname: Delorme
authors.forename: A
authors.initials: A
authors.lastname: Uzan
authors.forename: J G
authors.initials: JG
authors.lastname: Latour
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D001792:Blood Platelets / Q000473:pathology; D002478:Cells, Cultured; D004285:Dogs; D017984:Enoxaparin / Q000627:therapeutic use*; D004912:Erythrocytes / Q000473:pathology; D005260:Female; D006493:Heparin / Q000627:therapeutic use; D008297:Male; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000473:pathology; D009504:Neutrophils / Q000473:pathology; D010973:Platelet Adhesiveness / Q000187:drug effects; D013300:Streptokinase / Q000627:therapeutic use; D015912:Thrombolytic Therapy
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D006493:Heparin; D013300:Streptokinase