EFFECTS OF HEPARIN AND N-ACETYL HEPARIN ON ISCHEMIA/REPERFUSION-INDUCED ALTERATIONS IN MYOCARDIAL-FUNCTION IN THE RABBIT ISOLATED HEART
EFFECTS OF HEPARIN AND N-ACETYL HEPARIN ON ISCHEMIA/REPERFUSION-INDUCED ALTERATIONS IN MYOCARDIAL-FUNCTION IN THE RABBIT ISOLATED HEART
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DOI：
10.1161/01.res.75.4.701
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发表时间：
1994-10-01
影响因子：
20.1
通讯作者：
LUCCHESI, BR
中科院分区：
文献类型：
--
作者：
FRIEDRICHS, GS;KILGORE, KS;LUCCHESI, BR
有证据表明，肝素预处理对心肌组织产生的保护作用不同于其抗凝活性。本研究探讨硫酸肝素和N-乙酰肝素（一种没有抗凝作用的肝素衍生物）保护心脏免受全身缺血和再灌注损伤的能力。雄性新西兰白色家兔接受硫酸肝素（n=7，300 U/kg IV）、N-乙酰肝素（n=6，1.73 mg/kg IV）或溶媒（n=6）给药。处理后2小时，取出心脏，在Langendorff装置上灌注，并进行30分钟的全脑缺血，然后再灌注45分钟。在再灌注期间，与N-乙酰肝素治疗和肝素治疗的家兔心脏相比，溶媒治疗的家兔心脏冠状窦流出液中的肌酸激酶浓度更高。再灌注45分钟后，赋形剂治疗组的左心室舒张末期压为64+/-15 mm Hg，而肝素预处理组和N-乙酰肝素预处理组分别为17+/-4和10+/-3 mm Hg。肝素（而非N-乙酰肝素）延长了活化部分凝血活酶时间，与其已知的抗凝剂一致。行动上肝素和N-乙酰肝素以浓度依赖性方式抑制补体介导的红细胞溶解。在兔离体心脏中，与水蛭素相比，糖胺聚糖可减少补体激活引起的损伤。结果表明，肝素或N-乙酰肝素，给予完整的兔子，保护离体心脏继发于缺血/再灌注心肌功能障碍。肝素和N-乙酰肝素的心脏保护作用不依赖于抗凝血酶机制。
Evidence is presented that heparin pretreatment produces protective effects on myocardial tissue distinct from its anticoagulant activity. The present study examines the ability of heparin sulfate and N-acetyl heparin (a derivative of heparin devoid of anticoagulant effects) to protect the heart from injury associated with global ischemia and reperfusion. Male New Zealand White rabbits were administered either heparin sulfate (n=7, 300 U/kg IV), N-acetyl heparin (n=6, 1.73 mg/kg IV), or vehicle (n=6). Two hours after treatment, the hearts were removed, perfused on a Langendorff apparatus, and subjected to 30 minutes of global ischemia, followed by 45 minutes of reperfusion. During reperfusion, creatine kinase concentrations in the coronary sinus effluent were greater in hearts from vehicle-treated rabbits compared with hearts from N-acetyl heparin-treated and heparin-treated rabbits. Left ventricular end-diastolic pressure after 45 minutes of reperfusion in the vehicle-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 activated partial thromboplastin time, consistent with its known anticoagulant. action. Heparin and N-acetyl heparin inhibited complement-mediated erythrocyte lysis in a concentration-dependent manner. The glycosaminoglycans, in contrast to r-hirudin, reduced complement activation-induced injury in the rabbit isolated heart. The results demonstrate that heparin or N-acetyl heparin, administered to the intact rabbit, protects 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.