EFFECTS OF HEPARIN AND N-ACETYL HEPARIN ON ISCHEMIA REPERFUSION-INDUCED ALTERATIONS IN MYOCARDIAL-FUNCTION IN THE RABBIT ISOLATED HEART/

Evidence is presented that heparin pretreatment produces protective ef fects on myocardial tissue distinct from its anticoagulant activity. T he present study examines the ability of heparin sulfate and N-acetyl heparin (a derivative of heparin devoid of anticoagulant effects) to p rotect the heart from injury associated with global ischemia and reper fusion. Male New Zealand White rabbits were administered either hepari n sulfate (n=7, 300 U/kg IV), N-acetyl heparin (n=6, 1.73 mg/kg IV), o r vehicle (n=6). Two hours after treatment, the hearts were removed, p erfused on a Langendorff apparatus, and subjected to 30 minutes of glo bal ischemia, followed by 45 minutes of reperfusion. During reperfusio n, creatine kinase concentrations in the coronary sinus effluent were greater in hearts from vehicle-treated rabbits compared with hearts fr om N-acetyl heparin-treated and heparin-treated rabbits. Left ventricu lar end-diastolic pressure after 45 minutes of reperfusion in the vehi cle-treated group was 64+/-15 mm Hg compared with 17+/-4 and 10+/-3 mm Hg in the heparin-pretreated and N-acetyl heparin-pretreated groups, respectively. Heparin, but not N-acetyl heparin, increased the activat ed partial thromboplastin time, consistent with its known anticoagulan t. action. Heparin and N-acetyl heparin inhibited complement-mediated erythrocyte lysis in a concentration-dependent manner. The glycosamino glycans, in contrast to r-hirudin, reduced complement activation-induc ed injury in the rabbit isolated heart. The results demonstrate that h eparin or N-acetyl heparin, administered to the intact rabbit, protect s the isolated heart from subsequent myocardial dysfunction secondary to ischemia/reperfusion. The cardioprotective effects of heparin and N -acetyl heparin are independent of an antithrombin mechanism.