N-Acetylheparin pretreatment reduces infarct size in the rabbit.

Abstract

The ability of the heparin derivative, N-acetylheparin (NHEP) to protect the heart from regional ischemia/reperfusion injury was examined in vivo. NHEP (2 mg/kg i.v.) or vehicle was administered 2 h before occlusion of the left circumflex coronary (LCX) artery. Open-chest, anesthetized rabbits were subjected to 30 min of regional myocardial ischemia followed by 5 h of reperfusion. Myocardial myeloperoxidase activity, membrane attack complex (MAC) deposition and IL-8 generation were assessed in supernatant samples from the area at risk. Infarct size in rabbits pretreated with NHEP (32.5 +/- 3.8%, n = 10) decreased by 41% compared to infarct size in rabbits that received vehicle (55.3 +/- 4.9%, n = 10; p = 0.002). Accumulation of neutrophils within the ischemic region, as assessed by myeloperoxidase activity, declined by 45% (p < 0.05) in AAR from NHEP-treated animals compared to AAR from vehicle-treated animals. Levels of MAC and IL-8 obtained from AAR were less in NHEP-pretreated animals compared to controls. These results suggest that NHEP may protect the myocardium by inhibiting complement activation and subsequent neutrophil infiltration.

• Authors: J L Park, K S Kilgore, K B Naylor, E A Booth, K L Murphy, B R Lucchesi
• Journal: Pharmacology (Pharmacology) Vol. 58 Issue 3 Pg. 120-31 (Mar 1999) ISSN: 0031-7012 [Print] Switzerland
• PMID: 9925968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Complement Membrane Attack Complex
• Interleukin-8
• N-acetylheparin
• Heparin
• Peroxidase
• Calcium

Topics

• Animals
• Calcium (metabolism)
• Complement Membrane Attack Complex (metabolism)
• Hemodynamics (drug effects)
• Heparin (analogs & derivatives, pharmacology)
• Interleukin-8 (metabolism)
• Leukocyte Count
• Male
• Myocardial Infarction (drug therapy, metabolism, pathology)
• Myocardial Reperfusion Injury (metabolism, pathology, prevention & control)
• Myocardium (enzymology, pathology)
• Neutrophil Activation (drug effects)
• Peroxidase (metabolism)
• Rabbits