Kloner R A, Braunwald E, Maroko P R
Circulation. 1978 Aug;58(2):220-6. doi: 10.1161/01.cir.58.2.220.
The administration of hyaluronidase is a promising intervention to protect the ischemic myocardium in man, but evidence of the extent to which it may reduce the ultimate size of an infarct is not well-defined. Hence, open chest, anesthetized dogs were randomized into 10 control dogs which received saline and eight treated dogs which received three doses of hyaluronidase (500 NF units/kg I.V.) at 15 minutes, 2 hours and 24 hours after occlusion of the left anterior descending coronary artery (CAO). Regional myocardial blood flow (RMBF) assessed by the microsphere technique was measured 12 minutes after CAO. The chest was then closed and the dogs were allowed to recover. Twenty-one days after CAO, the hearts were excised, divided into 1 cm thick slices and incubated in triphenyl tetrazolium chloride. Infarct size was then determined by planimetry. The left ventricular myocardium was divided into multiple samples for RMBF analysis. In control dogs 23.2 +/- 2% of the left ventricle was infarcted, compared to only 9 +/- 2.8% (P less than 0.001) in hyaluronidase-treated dogs. RMBF in noninfarcted myocardium directly adjacent to the infarct was similar to that in the normal zone remote from the infarct in the control dogs; however, in the hyaluronidase-treated dogs, blood flow in the myocardium adjacent to the infarct was significantly reduced to 68% of normal (P less than 0.01) in the outer myocardial wall and to 86% of normal (P less than 0.02) in the inner myocardial wall, which indicates that this tissue, at least in some part, was in jeopardy, but was salvaged by hyaluronidase. Epicardial electrocardiographic data showed that three weeks after CAO, Q waves were less frequent and smaller in hyaluronidase compared to untreated dogs. Preservation of the frequency and magnitude of R waves was greater in the hyaluronidase-treated group at three weeks. We conclude that hyaluronidase resulted in long-term preservation of the ischemic myocardium.
透明质酸酶的应用是一种有望保护人类缺血心肌的干预措施，但关于其能在多大程度上减小梗死最终面积的证据尚不明确。因此，将开胸麻醉的犬随机分为10只接受生理盐水的对照犬和8只在左前降支冠状动脉闭塞（CAO）后15分钟、2小时和24小时接受三剂透明质酸酶（500 NF单位/千克静脉注射）的治疗犬。在CAO后12分钟，通过微球技术评估局部心肌血流量（RMBF）。然后关闭胸腔，让犬恢复。CAO后21天，取出心脏，切成1厘米厚的切片，置于氯化三苯基四氮唑中孵育。然后通过平面测量法确定梗死面积。将左心室心肌分成多个样本进行RMBF分析。对照犬左心室梗死面积为23.2±2%，而透明质酸酶治疗犬仅为9±2.8%（P<0.001）。对照犬中紧邻梗死灶的非梗死心肌中的RMBF与远离梗死灶的正常区域相似；然而，在透明质酸酶治疗犬中，梗死灶周边心肌的血流量在外膜壁显著降至正常的68%（P<0.01），在内膜壁降至正常的86%（P<0.02），这表明该组织至少部分处于危险之中，但被透明质酸酶挽救。心外膜心电图数据显示，CAO三周后，与未治疗犬相比，透明质酸酶组的Q波频率更低、幅度更小。三周时，透明质酸酶治疗组R波的频率和幅度保留得更好。我们得出结论，透明质酸酶可长期保护缺血心肌。
