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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
Journal of Cardiovascular Pharmacology and Therapeutics ( IF 2.6 ) Pub Date : 2020-09-09 , DOI: 10.1177/107424849600100305
Michael R. Gralinski 1 , Edward M. Driscoll 1 , Gregory S. Friedrichs 1 , Michael R. DeNardis 1 , Benedict R. Lucchesi 1
Affiliation  

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.

Conclusion

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.



中文翻译:

糖胺聚糖给药后心肌坏死的减少:局部缺血和再灌注前2小时静脉注射肝素或N-乙酰肝素的影响

背景

我们确定了单次给予肝素或非抗凝性N-乙酰肝素是否可以减轻因左旋支冠状动脉(LCX)阻塞90分钟和麻醉犬再灌注6小时而导致的心肌损伤。

方法与结果

在LCX闭塞前2小时,分别将肝素(2 mg / kg),N-乙酰肝素(2 mg / kg)或溶媒0.9%氯化钠(对照组)静脉内分开给药。为了确保LCX缺血的均等性,最终分析中仅包括缺血区域局部血流<0.16 mL / min / g组织的动物。三个研究组之间的血流动力学无差异。每组均获得梗塞面积占风险中左心室面积的百分比。在用N-乙酰肝素治疗的动物中,媒介物的心肌梗塞大小为43.0±3.9%,肝素为28.8±5.8%(对媒介物,P <.05)和24.7±4.6%(对媒介物,P <0.05)。

结论

用肝素或其非抗凝衍生物N-乙酰肝素进行预处理,可对局部缺血和再灌注的犬心肌提供显着的保护,而不受血浆糖胺聚糖浓度或凝血系统改变的影响。

更新日期:2020-09-10
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