RT Journal Article
SR Electronic
T1 Ex Vivo Reversal of Heparin-Mediated Cardioprotection by Heparinase After Ischemia and Reperfusion
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1041
OP 1047
VO 290
IS 3
A1 Kenneth S. Kilgore
A1 Elaine J. Tanhehco
A1 Keith B. Naylor
A1 Benedict R. Lucchesi
YR 1999
UL http://jpet.aspetjournals.org/content/290/3/1041.abstract
AB Glycosaminoglycans, including heparin, have been demonstrated both in vitro and in vivo to protect the ischemic myocardium against reperfusion injury. In the present study, we sought to determine whether the cardioprotective effects of heparin administration could be reversed by the heparin-degrading enzyme heparinase. New Zealand white rabbits were pretreated with heparin (300 U/kg i.v.) or vehicle (saline). Two hours after treatment, hearts were removed, perfused on a Langendorff apparatus, and subjected to 25 min of global ischemia, followed by 45 min of reperfusion. Hemodynamic variables were obtained before ischemia (baseline) and every 10 min throughout the reperfusion period. Compared with vehicle-treated rabbits, the left ventricular end-diastolic and left ventricular developed pressures were improved significantly (p < .05) in the heparin-treated group. Ex vivo administration of heparinase (5 U/ml) immediately before the onset of global ischemia was associated with a reversal of the heparin-mediated cardioprotection. The uptake of a radiolabeled antibody to the intracellular protein myosin and creatine kinase release were used to determine membrane integrity and discriminate between viable and nonviable myocardial tissue. The uptake of radiolabeled antimyosin antibody and release of creatine kinase after reperfusion were increased in heparin-pretreated hearts exposed to heparinase, indicating a loss of membrane integrity and increased myocyte injury. These results demonstrate that neutralization of heparin by heparinase promotes increased myocardial injury after reperfusion of the ischemic myocardium. The American Society for Pharmacology and Experimental Therapeutics