• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文OA文献 >Nonanticoagulant heparin reduces myocyte Na+ and Ca2+ loading during simulated ischemia and decreases reperfusion injury
【2h】

Nonanticoagulant heparin reduces myocyte Na+ and Ca2+ loading during simulated ischemia and decreases reperfusion injury

机译：非抗凝肝素可减少模拟缺血期间心肌细胞Na +和Ca2 +的负载并减少再灌注损伤

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务，本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文，但由于OA文献来源多样且变更频繁，仍可能出现获取不到、文献不完整或与标题不符等情况，如果获取不到我们将提供退款服务。请知悉。
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Heparin desulfated at the 2-O and 3-O positions (ODSH) decreases canine myocardial reperfusion injury. We hypothesized that this occurs from effects on ion channels rather than solely from anti-inflammatory activities, as previously proposed. We studied closed-chest pigs with balloon left anterior descending coronary artery occlusion (75-min) and reperfusion (3-h). ODSH effects on [Na+]i (Na Green) and [Ca2+]i (Fluo-3) were measured by flow cytometry in rabbit ventricular myocytes after 45-min of simulated ischemia [metabolic inhibition with 2 mM cyanide, 0 glucose, 37°C, pacing at 0.5 Hz; i.e., pacing-metabolic inhibition (PMI)]. Na+/Ca2+ exchange (NCX) activity and Na+ channel function were assessed by voltage clamping. ODSH (15 mg/kg) 5 min before reperfusion significantly decreased myocardial necrosis, but neutrophil influx into reperfused myocardium was not consistently reduced. ODSH (100 μg/ml) reduced [Na+]i and [Ca2+]i during PMI. The NCX inhibitor KB-R7943 (10 μM) or the late Na+ current (INa-L) inhibitor ranolazine (10 μM) reduced [Ca2+]i during PMI and prevented effects of ODSH on Ca2+ loading. ODSH also reduced the increase in Na+ loading in paced myocytes caused by 10 nM sea anemone toxin II, a selective activator of INa-L. ODSH directly stimulated NCX and reduced INa-L. These results suggest that in the intact heart ODSH reduces Na+ influx during early reperfusion, when INa-L is activated by a burst of reactive oxygen production. This reduces Na+ overload and thus Ca2+ influx via NCX. Stimulation of Ca2+ extrusion via NCX later after reperfusion may also reduce myocyte Ca2+ loading and decrease infarct size.
机译：肝素在2-O和3-O位置（ODSH）脱硫可减少犬心肌再灌注损伤。我们假设这是由于对离子通道的影响，而不是像先前提出的那样，仅是由于抗炎活性引起的。我们研究了球囊左冠状动脉前降支闭塞（75分钟）和再灌注（3小时）的闭胸猪。在模拟缺血45分钟后，通过流式细胞术测定兔心室肌细胞中[Na +] i（Na Green）和[Ca2 +] i（Fluo-3）的ODSH效应[2 mM氰化物，0葡萄糖，37°的代谢抑制作用] C，以0.5 Hz起搏；即起搏代谢抑制（PMI）]。 Na + / Ca2 +交换（NCX）活性和Na +通道功能通过电压钳制进行评估。再灌注前5分钟的ODSH（15 mg / kg）明显减少了心肌坏死，但中性粒细胞向再灌注心肌的流入并没有持续减少。 ODSH（100μg/ ml）在PMI期间降低[Na +] i和[Ca2 +] i。 NCX抑制剂KB-R7943（10μM）或晚期Na +电流（INa-L）抑制剂雷诺嗪（10μM）在PMI期间降低[Ca2 +] i，并防止ODSH对Ca2 +负载的影响。 ODSH还减少了由10nM海葵毒素II（一种INa-L的选择性激活剂）引起的节律性心肌细胞Na +负荷的增加。 ODSH直接刺激NCX并降低INa-L。这些结果表明，在完整的心脏中，ODSH会减少早期再灌注期间的Na +流入，此时INa-L被活性氧产生的爆发所激活。这样可以减少Na +过载，从而减少Ca2 +通过NCX流入。再灌注后稍后通过NCX刺激Ca2 +挤出也可能减少心肌细胞的Ca2 +负荷并减小梗塞面积。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号