Reduction of Myocardial Necrosis After Glycosaminoglycan Administration: Effects of a Single Intravenous Administration of Heparin or N-Acetylheparin 2 Hours Before Regional Ischemia and Reperfusion.
BACKGROUND: We determined if a single administration of heparin or nonanticoagulant N-acetylheparin could reduce myocardial injury resulting from a 90-minute occlusion of the left circumflex coronary artery (LCX) and 6 hours of reperfusion in the anesthetized canine. METHODS AND RESULTS: Heparin (2 mg/kg), N-acetylheparin (2 mg/kg), or vehicle, 0.9% sodium chloride (control), was administered intravenously to separate groups of animals 2 hours before LCX occlusion. To ensure parity of LCX ischemia, only animals with ischemic zone regional blood flow < 0.16 mL/min/g tissue were included in the final analysis. Hemodynamics did not differ among the three study groups. Infarct size as a percentage of the left ventricular area at risk was obtained for each group. Myocardial infarct size was 43.0 +/- 3.9% in the vehicle, 28.8 +/- 5.8% in the heparin (P <.05 vs vehicle) and 24.7 +/- 4.6% (P <.05 vs vehicle) in the N-acetylheparin-treated animals. CONCLUSIONS: Pretreatment with heparin or its nonanticoagulant derivative, N-acetylheparin, provides significant protection to the regionally ischemic and reperfused canine myocardium independent of either plasma glycosaminoglycan concentration or alterations in the coagulation system.
Gralinski
MR
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, Michigan, USA
Driscoll
EM
Friedrichs
GS
DeNardis
MR
Lucchesi
BR